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  • 301.
    Tabar, Laszlo
    et al.
    Falun Central Hospital, Falun.
    Vitak, Bedrich
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Hsiu-Hsi Chen, Tony
    National Taiwan University,Taipei, Taiwan.
    Ming-Fang Yen, Amy
    Taipei Medical University, Taipei, Taiwan.
    Cohen, Anders
    Falun Central Hospital, Falun.
    Tot, Tibor
    Falun Central Hospital, Falun.
    Yueh-Hsia Chiu, Sherry
    Chang Gung University, Taoyuan, Taiwan.
    Li-Sheng Chen, Sam
    Taipei Medical University, Taipei, Taiwan.
    Ching-Yuan Fann, Jean
    Kainan University, Taoyuan, Taiwan.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Fohlin, Helena
    Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi.
    Smith, Robert A
    American Cancer Society, Atlanta, USA.
    Duffy, Stephen W
    Queen Mary University of London, London, UK.
    Swedish Two-County Trial: Impact of Mammographic Screening on Breast Cancer Mortality during 3 Decades2011Inngår i: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 260, nr 3, s. 658-663Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To estimate the long-term (29-year) effect of mammographic screening on breast cancer mortality in terms of both relative and absolute effects. less thanbrgreater than less thanbrgreater thanMaterials and Methods: This study was carried out under the auspices of the Swedish National Board of Health and Welfare. The board determined that, because randomization was at a community level and was to invitation to screening, informed verbal consent could be given by the participants when they attended the screening examination. A total of 133 065 women aged 40-74 years residing in two Swedish counties were randomized into a group invited to mammographic screening and a control group receiving usual care. Case status and cause of death were determined by the local trial end point committees and, independently, by an external committee. Mortality analysis was performed by using negative binomial regression. less thanbrgreater than less thanbrgreater thanResults: There was a highly significant reduction in breast cancer mortality in women invited to screening according to both local end point committee data (relative risk [RR] = 0.69; 95% confi dence interval: 0.56, 0.84; P andlt;.0001) and consensus data (RR = 0.73; 95% confi dence interval: 0.59, 0.89; P =.002). At 29 years of follow-up, the number of women needed to undergo screening for 7 years to prevent one breast cancer death was 414 according to local data and 519 according to consensus data. Most prevented breast cancer deaths would have occurred (in the absence of screening) after the first 10 years of follow-up. less thanbrgreater than less thanbrgreater thanConclusion: Invitation to mammographic screening results in a highly significant decrease in breast cancer-specific mortality. Evaluation of the full impact of screening, in particular estimates of absolute benefit and number needed to screen, requires follow-up times exceeding 20 years because the observed number of breast cancer deaths prevented increases with increasing time of follow-up.

  • 302.
    Tell, Roger
    et al.
    Karolinska University Hospital.
    Sederholm, Christer
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet.
    Klintenberg, Claes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Franksson, Lars
    Karolinska University Hospital.
    Branden, Eva
    Karolinska University Hospital.
    Hillerdal, Gunnar
    Karolinska University Hospital.
    Lonn, Ulf
    Gävle City Hospital.
    Linden, Carl-Johan
    Lund University Hospital.
    Ewers, Sven-Borje
    Lund University Hospital.
    Lamberg, Kristina
    Västerås Hospital.
    Mrazek, Eva
    Västerås Hospital.
    Loden, Britta
    Karlstad Central Hospital.
    Sjogren, Anders
    Karlstad Central Hospital.
    Linne, Thomas
    Bristol Myers Squibb AB.
    Friesland, Signe
    Karolinska University Hospital.
    Sirzen, Florin
    Karolinska University Hospital.
    Multicentre Phase II Trial of Paclitaxel and Carboplatin with Concurrent Radiotherapy in Locally Advanced Non-small Cell Lung Cancer2008Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, nr 5B, s. 2851-2857Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To evaluate weekly, induction chemotherapy followed by weekly concomitant chemoradiotherapy in a multicentre phase II study of patients with wiresectable stage III non-small cell lung cancer (NSCLC; stage wet IIIB excluded). Patients (aid Methods: Eligible patients received three weekly cycles of paclitaxel 100 mg/m(2) and carboplatin AUC2 followed by six weekly cycles of paclitaxel 60 mg/m(2) and carboplatin AUC2 in combination with thoracic radiotherapy (2 Gy per fraction and day to a total (lose of 60 Gy), Results: Sixty-four patients (40 males and 24 females) with a median age of 63 Years (range, 43-79 years) entered the study. T and N stage were distributed as follows: T1 2 patients (3.2%). T2 10 patients (15.6%), T3 15 patients (23.4%). T4 37 patients (57.8%), N0 10 patients (15.6%). N1 1 patient (1.6%), N2 26 patients (40.6%), N3 26 patients (40.6%), and N missing I patient (1.6%). Seven patients (10.9%) suffered from grade 314 oesophagitis. Grade 112 oesophagitis occurred in 36 patients (56.3%) and pneumonitis grade 112 occurred in 10 patients (15.6%). Sixty-three patients were evaluated on an intent-to-treat basis. The overall response rate was 74.6%. The median time to progression was 247 days and median overall survival was 461 days. According to subgroup analyses, no statistically signicant differences were noted according to gender, age (<65 vs. >= 65 years), perfromance status, histology, or study centre. Conclusion: Induction chemotherapy followed by concurrent chemoradiotherapy with weekly cycles of paclitaxel and carboplatin is feasible and generates moderate toxicity. Efficacy is comparable to other recently published regimens. However, prognosis remains, ill general, poor for this group of patients and further work to develop better therapy is required.

  • 303. Tobin, G
    et al.
    Thunberg, U
    Johnson, A
    Eriksson, I
    Soderberg, O
    Karlsson, K
    Merup, M
    Enblad, G
    Juliusson, Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Vilpo, J
    Sundstrom, C
    Roos, G
    Rosenquist, R
    V(a)3-21 gene utilizing chronic lymphocytic leukemias display restricted V lambda 2-14 gene usage and homologous CDR3s.2002Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, nr 11, s. 362-Konferansepaper (Annet vitenskapelig)
  • 304. Tobin, G
    et al.
    Thunberg, U
    Johnson, A
    Eriksson, I
    Soderberg, O
    Karlsson, Karin
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Hematologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken.
    Merup, M
    Juliusson, Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Vilpo, J
    Enblad, G
    Sundstrom, C
    Roos, G
    Rosenquist, R
    Chronic lymphocytic leukemias utilizing the V(H)3-21 gene display highly restricted V(lambda)2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope2003Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 101, nr 12, s. 4952-4957Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The immunoglobulin variable heavy chain (IgV(H)) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated V-H genes show significantly longer survival than unmutated cases. Recently, we reported a preferential use of the V(H)3-21 gene in mutated CLL and showed that mutated V(H)3-21 cases had an inferior overall survival compared with other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 V(H)3-21 cases (11.7%), 21 cases had mutated and 10 cases unmutated VH genes. Regardless Of VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. These survival data confirm that V(H)3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction Of V(H)3-21 cases also demonstrated unique features with shorter lengths of the third complementarity determining region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the V(H)3-21 cases showed a striking dominance of X light chain expression, and analysis of the Iglambda gene rearrangements revealed highly restricted use of the Vlambda2-14/J(lambda)3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that V(H)3-21-using cases comprise a new CLL entity, irrespective Of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous V(H)3-21/V(lambda)2-14 Ig molecules expressed in individual tumors. (Blood. 2003,101:4952-4957).

  • 305.
    Trinks, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Djerf, Emelie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Hallbeck, Anna-Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell hematologi. Linköpings universitet, Hälsouniversitetet.
    Walz, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    The pan-ErbB receptor tyrosine kinase inhibitor canertinib induces ErbB-independent apoptosis in human leukemia (HL-60 and U-937) cells2010Inngår i: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ISSN 0006-291X, Vol. 393, nr 1, s. 6-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epidermal growth factor (EGF) receptor tyrosine kinase inhibitors have recently been shown to display anti-neoplastic effects in human malignant myeloid cells. Our study was initiated in order to determine the effect of the pan-ErbB receptor tyrosine kinase inhibitor, canertinib (CI-1033), on growth and survival of human leukemia (HL-60 and U-937) cells. We show that treatment of HL-60 and U-937 cells with canertinib significantly inhibits growth of both cell lines in a dose-dependent manner; half maximal effective dose (IC50) in HL-60 and U-937 cells was approximately 2.5 mu M and 1.0 mu M, respectively. Treatment with 2 mu M canertinib promoted a G(1) cell cycle arrest, whereas doses of 5 mu M or more induced apoptosis as determined by the Annexin V method and cleavage of poly-(ADP-ribose) polymerase (PARP). HL-60 and U-937 cells lacked EGF-receptor transcript but expressed ErbB2-4 mRNA as determined by RTPCR. However, none of the corresponding ErbB-receptor proteins could be detected by Western blot analysis. We conclude that canertinib induces apoptosis in HL-60 and U-937 cells devoid of functional ErbB1-4 receptors. Our results suggest that canertinib could be of potential clinical interest in the treatment of acute myeloid leukemia.

  • 306.
    Trinks, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell hematologi. Linköpings universitet, Hälsouniversitetet.
    Walz, Thomas M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Human leukemic cell lines express a truncated intracellular 160 kDa ERBB2 receptorManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    It has recently been demonstrated that ERBB specific tyrosine kinase inhibitors display antineoplastic activity in human leukemic cell devoid of functional ERBB receptors. The present study was undertaken in order to identify any putative target for these drugs. Flow cytometry experiments demonstrate the presence of an immunoreactive ERBB2 protein of intracellular localization and Western blot analysis visualized an ERBB2 protein of approximately 160 kDa. Exposing leukemia cells to tunicamycin did not alter the size of the truncated ERBB2 protein. The ERBB2 gene was alternative spliced with an absence of exon 5 containing the start codon for the full-length protein. In conclusion we demonstrate a nonglycosylated 160 kDa ERBB2-receptor protein with an alternative in-frame start codon in human leukemia cell lines.

  • 307.
    Trinks, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Severinsson, Emelie A.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Gréen, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell hematologi. Linköpings universitet, Hälsouniversitetet.
    Hallbeck, Anna-Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Walz, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    The pan-ErbB tyrosine kinase inhibitor canertinib induces caspase-mediated cell death in human T-cell leukemia (Jurkat) cells2011Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 410, nr 3, s. 422-427Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Canertinib is a novel ErbB-receptor inhibitor currently in clinical development for the treatment of solid tumors overexpressing ErbB-receptors. We have recently demonstrated that canertinib displays anti-proliferative and pro-apoptotic effects in human myeloid leukemia cells devoid of ErbB-receptors. The mechanism mediating these effects are however unknown. In this study, we show that canertinib is able to act as a multi-kinase inhibitor by inhibition of several intracellular kinases involved in T-cell signaling such as Akt, Erk1/2 and Zap-70, and reduced Lck protein expression in the human T-cell leukemia cell line Jurkat. Treatment with canertinib at a concentration of 2 mu M caused accumulation of Jurkat cells in the G(1) cell cycle phase and increased doses induced apoptosis in a time-dependent manner. Apoptotic signs of treated cells were detected by Annexin V staining and cleavage of PARP, caspase-3, -8, -9, -10 and Bid. A subset of the pro-apoptotic signals mediated by canertinib could be significantly reduced by specific caspase inhibitors. Taken together, these results demonstrate the dual ability of canertinib to downregulate important signaling pathways and to activate caspase-mediated intrinsic apoptosis pathway in human T-cell leukemia cells.

  • 308.
    Tveit, Kjell Magne
    et al.
    Oslo University Hospital, Norway.
    Guren, Tormod
    Uppsala Hospital, Sweden Karolinska Institute, Sweden .
    Pfeiffer, Per
    Odense University Hospital, Denmark .
    Sorbye, Halfdan
    Haukeland Hospital, Norway University of Bergen, Norway .
    Pyrhonen, Seppo
    Turku University Hospital, Finland .
    Sigurdsson, Fridbjorn
    National University Hospital Reykjavik, Iceland .
    Kure, Elin
    University of Oslo, Norway .
    Fokstuen, Tone
    Karolinska Institute, Sweden .
    Hansen, Flemming
    Aarhus University Hospital, Denmark .
    Hofsli, Eva
    St Olavs Hospital, Norway .
    Birkemeyer, Elke
    Stavanger University Hospital, Norway .
    Johnsson, Anders
    University of Lund Hospital, Sweden .
    Starkhammar, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Karen Yilmaz, Mette
    Aalborg University Hospital, Denmark .
    Keldsen, Nina
    Herning Regional Hospital, Denmark .
    Berit Erdal, Anne
    Haukeland Hospital, Norway University of Bergen, Norway .
    Christoffersen, Thoralf
    University of Oslo, Norway .
    Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study2012Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, nr 15, s. 1755-1762Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose less thanbrgreater than less thanbrgreater thanThe NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. less thanbrgreater than less thanbrgreater thanPatients and Methods less thanbrgreater than less thanbrgreater thanPatients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanOf the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. less thanbrgreater than less thanbrgreater thanConclusion less thanbrgreater than less thanbrgreater thanCetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.

  • 309.
    Törnroos, Alexander
    et al.
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    The number of identified lymph node metastases increases continuously with increased total lymph node recovery in pT3 colon cancer2009Inngår i: ACTA ONCOLOGICA, ISSN 0284-186X, Vol. 48, nr 8, s. 1152-1156Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. The positive correlation between the number of recovered benign lymph nodes and patient prognosis is well established for stage II colon cancer patients. One theory explaining this correlation focuses on potential understaging of cancer specimen, implying that a specimen with few examined lymph nodes is likely to be assigned a lower N-stage than the correct one. Understaging may be the result of an insufficient examination of the specimen post-operatively, whereby few lymph nodes are recovered and potential lymph node metastases are overlooked. This study aims to investigate the association between the total lymph node harvest and the number of lymph node metastases in colon cancer specimen. Material and methods. We studied the original pathology reports of 649 patients diagnosed with T3 adenocarcinoma of the colon at the Department of Clinical Pathology and Genetics at Linkoping University Hospital, Linkoping, Sweden between the years 2000 and 2008. Patient demographics, specimen staging data, and lymph node recovery data were collected for each case. Results. We found a positive association between the total lymph node harvest and the number of lymph node metastases per specimen. For every additional recovered lymph node 0.17 (95% CI: 0.15-0.19) metastases were detected (pandlt;0.001). Discussion. Our results support the conclusion that there is no minimum number of recovered lymph nodes at which an accurate determination of nodal status can be assured. Rather than focusing on a recommended minimum number of nodes, efforts should be shifted towards developing methods assuring that colon cancer specimen are dissected in a standardized way that optimizes the lymph node harvest.

  • 310. Waage, A
    et al.
    Romstad, L
    Brenne, AT
    Gimsing, P
    Juliusson, Gunnar
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Turesson, I
    Borset, M
    Sundan, A
    Low serum levels of soluble tumor necrosis factor receptors predict for response to thalidomide in advanced myeloma.2002Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 100, nr 11, s. 5082-Konferansepaper (Annet vitenskapelig)
  • 311.
    Waage, Anders
    et al.
    NTNU.
    Gimsing, Peter
    Rigshospital, Copenhagen.
    Fayers, Peter
    Norwegian University Science and Technology.
    Abildgaard, Niels
    Odense University Hospital.
    Ahlberg, Lucia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Bjorkstrand, Bo
    Karolinska University Hospital.
    Carlson, Kristina
    University Uppsala Hospital.
    Dahl, Inger Marie
    University Tromso Hospital.
    Forsberg, Karin
    Norrland University Hospital.
    Gulbrandsen, Nina
    University of Oslo.
    Haukas, Einar
    Stavanger University Hospital.
    Hjertner, Oyvind
    Norwegian University Science and Technology.
    Hjorth, Martin
    Lidkoping Hospital.
    Karlsson, Torbjorn
    Capio Sankt Gorans Hospital.
    Meldgaard Knudsen, Lene
    Herlev Hospital.
    Lanng Nielsen, Johan
    Aarhus University Hospital.
    Linder, Olle
    Orebro University Hospital.
    Mellqvist, Ulf-Henrik
    Sahlgrens University Hospital.
    Nesthus, Ingerid
    Haukeland Hospital.
    Rolke, Jurgen
    Kristiansand Hospital.
    Strandberg, Maria
    Sundsvalls Hospital.
    Wisloff, Finn
    University of Oslo.
    Juliusson, Gunnar
    Lund University Hospital.
    Turesson, Ingemar
    Malmo University Hospital.
    Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma2010Inngår i: BLOOD, ISSN 0006-4971, Vol. 116, nr 9, s. 1405-1412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P andlt; .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, non-neuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855.

  • 312.
    Wallin, Åsa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Molecular Studies of Irradiation and SN-38 on Colorectal Cancer2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Colorectal cancer (CRC) is one of most common cancer diseases worldwide. In Swedenapproximately 5,000 new cases of CRC are generated each year, which makes it the thirdmost common cancer disease among both men and women. The past decades ofimproved treatment strategies have considerably increased the five-year survival for CRCpatients. However more could be achieved in this area, in particular for metastatic CRC,which is the cause of most CRC-related deaths. Therefore it is important to study thebiological response to certain treatments induced in CRC to find valuable predictiveand/or prognostic factors to select patients for better suited treatments.

    The aim of this thesis was to gain insight into the molecular changes that occurfollowing irradiation or treatment with SN-38 in rectal cancer patients or colon cancercell lines by studying the RNA expression, protein expression, DNA cell cycledistribution and apoptotic response. The expression of phosphatase of regenerating liver(PRL) proteins was investigated in rectal cancers from 125 patients included in arandomized clinical trial of preoperative radiotherapy (RT). Increased expression of PRLswas seen at the invasive margin of primary and metastatic cancers compared with theinner area of the tumors. Moreover, strong PRL staining at the invasive margin correlatedto distant recurrence and worse survival of patients in the RT group but not in non-RTgroup (Paper I). Radiosensitivity was studied by treating KM12C, KM12SM andKM12L4a colon cancer cell lines with radiation. KM12C is of low metastatic naturecompared with the highly metastatic KM12SM and KM12L4a. Upregulation of ΔNp73and PRL-3 might contribute to the radioresistant phenotype in KM12C. In contrast,KM12L4a shows a high frequency of apoptosis and lack of upregulation of ΔNp73, PRL-3 and survivin, which might explain its radiosensitive phenotype (Paper II). KM12C,KM12SM and KM12L4a were treated with SN-38 which inhibits topoisomerase 1 (topo-1). The results show that SN-38 induces G2/S arrest and possess the capacity to triggerapoptosis in the three cell lines (Paper III). To further elucidate SN-38 effect on these celllines, the gene expression profile following SN-38 treatment was studied. Oligonucleotidearrays consisting of ~27,000 spots were hybridized with sample and reference cDNA.Both unsupervised and supervised hierarchical clustering analysis, and functional analysiswere performed. Supervised hierarchical clustering gives a strong signal of 1453discriminated genes, the vast majority being upregulated. Both upregulated anddownregulated genes point toward a favorable impact of SN-38 regarding the apoptoticpathways. For example RhoB and Bax are upregulated together with downregulation ofKras and survivin, which promotes apoptosis (Paper IV).

    In conclusion, PRLs may be valuable biomarkers for RT resistance, predicting apoor prognosis in rectal cancer patients. Targeting radio-resistance factors, such asΔNp73 and survivin may contribute to an increased sensitivity to RT. SN-38 affects cellproliferation and apoptosis.

    Delarbeid
    1. Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy
    Åpne denne publikasjonen i ny fane eller vindu >>Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy
    2006 (engelsk)Inngår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, nr 2, s. 452-458Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients.

    Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT.

    Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes’ stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01).

    Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

    Emneord
    Phosphatase of regenerating liver; PRL; Invasive margin; Radiotherapy; Prognosis; Rectal cancer
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14784 (URN)10.1016/j.ijrobp.2005.12.043 (DOI)16626893 (PubMedID)
    Tilgjengelig fra: 2008-09-24 Laget: 2008-09-24 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells with mutant p53
    Åpne denne publikasjonen i ny fane eller vindu >>Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells with mutant p53
    2009 (engelsk)Inngår i: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 135, nr 11, s. 1583-1592Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We previously found that p53, p73, survivin and PRL were implicated in the outcome of radiotherapy in rectal cancer patients. In the present study, we tried to understand mechanisms of colon cancer cell line response to radiation based on protein expression related to proliferation and apoptosis. KM12C, KM12SM and KM12L4a, cell lines with one origin, were radiated with 0, 10 or 15 Gy γ-radiation. Radiosensitivity was determined with cell cycle and apoptosis analysis, and protein expression of TAp73, ΔNp73, mutated p53, survivin and PRL-3 was determined by Western blot. KM12C showed transient G2-arrest, low apoptosis and up-regulation of resistance factors such as PRL-3. In KM12C expression of ΔNp73 increased after 10Gy, but not after 15Gy. KM12SM had permanent G2-arrest, low apoptosis and showed up-regulation of the anti-apoptotic survivin and down-regulation of the pro-apoptotic TAp73 and the radioresistance factor PRL-3 was down-regulated. KM12L4a, the most radiosensitive cell line, showed up-regulation of TAp73 and down-regulation/no up-regulation of resistance factors such as ΔNp73, survivin and PRL-3 after radiation. In conclusion, the KM12C cell line was more radioresistant than KM12L4a regarding apoptosis and certain apoptotic proteins. The radiosensitivity of KM12L4a might partly depend on the lack of up-regulation of proteins negative for the outcome of radiotherapy.

     

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14786 (URN)10.1007/s00432-009-0606-4 (DOI)
    Tilgjengelig fra: 2008-09-24 Laget: 2008-09-24 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential
    Åpne denne publikasjonen i ny fane eller vindu >>Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential
    Vise andre…
    2008 (engelsk)Inngår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 19, nr 6, s. 1493-1498Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    SN-38 is an active metabolite of the topoisomerase I inhibitor irinotecan. The mechanism behind its antitumor effect in colorectal cancer is not fully understood. In this study, we examined the response of colon cancer cell lines with different metastatic potential to SN-38. The parental human colon cancer cell line KM12C and its two highly metastatic derivatives KM12SM and KM12L4a were cultivated in 5% CO2 at 37°C for 24 h and then exposed to SN-38 (2.5 µg/ml) at 37°C for 4, 24 and 48 h, respectively. The cell cycle was measured by flow cytometry, apoptotic activity was determined by flow cytometry and immunocytochemistry and the expression of topoisomerase I, Bax and survivin proteins were examined by Western blot. The exposure of the cells to SN-38 induced S-phase and G2 arrest (P<0.0001) and the KM12L4a cells had the highest response in a time-dependent manner (P<0.0001). The rates of apoptosis in the KM12SM (P=0.001) and KM12L4a cell lines (P=0.01) were increased time-dependently, though there was no such change in the KM12C cells. The expression of topoisomerase I protein was decreased in each cell line tested and the expression of Bax protein was increased, especially in KM12L4a. In conclusion, the effect of SN-38 on the colon cancer cell lines was mediated via conducting S-phase and G2 arrest and apoptosis. This effect was found in the cell lines with higher metastatic potentials, indicating that SN-38 can be used to treat advanced colon cancers.

    Emneord
    Colon cancer cell lines, SN-38, apoptosis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14787 (URN)10.3892/or.19.6.1493 (DOI)
    Tilgjengelig fra: 2008-09-24 Laget: 2008-09-24 Sist oppdatert: 2017-12-13
    4. Gene expression profile of colon cancer cell lines treated with SN-38
    Åpne denne publikasjonen i ny fane eller vindu >>Gene expression profile of colon cancer cell lines treated with SN-38
    Vise andre…
    2010 (engelsk)Inngår i: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 56, nr 1, s. 17-25Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aim: Colorectal cancer is the third most common form of cancer in the industrialcountries. Due to advances regarding the treatments, primarily development ofimproved surgical methods, and the ability to make the earlier diagnosis, the mortalityhas remained constant during the past decades even though the incidence in fact hasincreased. To improve chemotherapy and enable personalised treatment, the need ofbiomarkers is of great significance. In this study we evaluated the gene expressionprofiles of the colon cancer cell lines treated with SN-38, the active metabolite oftopoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis.Material and Methods: The study included three colon cancer cell lines KM12C,KM12SM and KM12l4a. The three cell lines were treated with SN-38, and sampleswere obtained after 24 and 48 hour treatments. The gene expression analyses wereperformed using oligonucleotide microarrays comprising of ~27,000 spots where theuntreated controls were compared to the SN-38 treated samples. Results: Unsupervisedclustering clearly distinguished the treated cell lines from the untreated. Supervisedanalysis identified 3974 significant genes (p=0.05) differentiating the treated samplesfrom the untreated, majority of which were downregulated after treatment. The toprankeddownregulated genes in the treated cell lines included those related to receptorand kinase activity, signal transduction, apoptosis, RNA processing, protein metabolismand transport, cell cycle and transcription. A smaller number of genes were upregulatedin the cell lines after treatment and included genes involved in apoptosis, transcription,development and differentiation. Conclusions: These results demonstrate that theexpression of the genes involved in cell proliferation and apoptosis as well as RNA,DNA and protein metabolism were affected by SN-38. The impact of certain genes oncolorectal cancer development needs to be further evaluated, however these resultscould serve as a basis for further studies in order to find targets for irinotecan treatment.

    sted, utgiver, år, opplag, sider
    S. Karger AG, 2010
    Emneord
    Colorectal, oncology, cancer
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14788 (URN)10.1159/000287353 (DOI)000276593500003 ()
    Merknad
    Original Publication: Åsa Wallin, P. Francis, N. Nilbert, Joar Svanvik and Xiao-Feng Sun, Gene expression profile of colon cancer cell lines treated with SN-38, 2010, Chemotherapy, (56), 1, 17-25. http://dx.doi.org/10.1159/000287353 Copyright: S. Karger AG http://www.karger.com/ Tilgjengelig fra: 2008-09-24 Laget: 2008-09-24 Sist oppdatert: 2017-12-13
  • 313.
    Wallin, Åsa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Francis, P.
    Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden.
    Nilbert, N.
    Department of Oncology, Institute of Clinical Sciences, Lund University, Lund, Sweden.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Gene expression profile of colon cancer cell lines treated with SN-382010Inngår i: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 56, nr 1, s. 17-25Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Colorectal cancer is the third most common form of cancer in the industrialcountries. Due to advances regarding the treatments, primarily development ofimproved surgical methods, and the ability to make the earlier diagnosis, the mortalityhas remained constant during the past decades even though the incidence in fact hasincreased. To improve chemotherapy and enable personalised treatment, the need ofbiomarkers is of great significance. In this study we evaluated the gene expressionprofiles of the colon cancer cell lines treated with SN-38, the active metabolite oftopoisomerase-1 inhibitor irinotecan which leads to cell cycle arrest and apoptosis.Material and Methods: The study included three colon cancer cell lines KM12C,KM12SM and KM12l4a. The three cell lines were treated with SN-38, and sampleswere obtained after 24 and 48 hour treatments. The gene expression analyses wereperformed using oligonucleotide microarrays comprising of ~27,000 spots where theuntreated controls were compared to the SN-38 treated samples. Results: Unsupervisedclustering clearly distinguished the treated cell lines from the untreated. Supervisedanalysis identified 3974 significant genes (p=0.05) differentiating the treated samplesfrom the untreated, majority of which were downregulated after treatment. The toprankeddownregulated genes in the treated cell lines included those related to receptorand kinase activity, signal transduction, apoptosis, RNA processing, protein metabolismand transport, cell cycle and transcription. A smaller number of genes were upregulatedin the cell lines after treatment and included genes involved in apoptosis, transcription,development and differentiation. Conclusions: These results demonstrate that theexpression of the genes involved in cell proliferation and apoptosis as well as RNA,DNA and protein metabolism were affected by SN-38. The impact of certain genes oncolorectal cancer development needs to be further evaluated, however these resultscould serve as a basis for further studies in order to find targets for irinotecan treatment.

  • 314.
    Wallin, Åsa R.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Adell, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Expression of PRL proteins at invasive margin of rectal cancers in relation to preoperative radiotherapy2006Inngår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, nr 2, s. 452-458Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: PRL-3 (phosphatase of regenerating liver) is involved in metastasis of colorectal cancer; however, its therapeutic implication in cancer patients has not been studied. We investigated the relationships of PRL expression to radiotherapy (RT) in rectal cancer patients.

    Methods and Materials: Phosphatase of regenerating liver expression was immunohistochemically examined in distant (n = 36) and adjacent (n = 82) normal mucosa, primary tumor (n = 125), biopsy specimens (n = 96), and lymph node metastasis (n = 30) from rectal cancer patients participating in a clinical trial of preoperative RT.

    Results: Phosphatase of regenerating liver expression was increased from the distant to adjacent mucosa and to the primary tumor (p < 0.05). PRL was highly expressed at the invasive margin in 28% of the primary tumors and 26% of the metastases. In the RT group, strong PRL expression at the invasive margin was related to distant recurrence (p = 0.006) and poor survival (p = 0.01), but not in the non-RT group. The survival significance remained even after adjusting for Dukes’ stage and differentiation (p = 0.02). Additional multivariate analyses showed that the correlation with prognostic significance of PRL differed between the RT and non-RT groups (p = 0.01).

    Conclusion: Phosphatase of regenerating liver expression (rather than PRL-3 alone) at the invasive margin predicted resistance to RT and unfavorable survival in rectal cancer patients with preoperative RT.

  • 315.
    Wallin, Åsa
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Svanvik, Joar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Ferreud, Lillianne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Anticancer effect of SN-38 on colon cancer cell lines with different metastatic potential2008Inngår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 19, nr 6, s. 1493-1498Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    SN-38 is an active metabolite of the topoisomerase I inhibitor irinotecan. The mechanism behind its antitumor effect in colorectal cancer is not fully understood. In this study, we examined the response of colon cancer cell lines with different metastatic potential to SN-38. The parental human colon cancer cell line KM12C and its two highly metastatic derivatives KM12SM and KM12L4a were cultivated in 5% CO2 at 37°C for 24 h and then exposed to SN-38 (2.5 µg/ml) at 37°C for 4, 24 and 48 h, respectively. The cell cycle was measured by flow cytometry, apoptotic activity was determined by flow cytometry and immunocytochemistry and the expression of topoisomerase I, Bax and survivin proteins were examined by Western blot. The exposure of the cells to SN-38 induced S-phase and G2 arrest (P<0.0001) and the KM12L4a cells had the highest response in a time-dependent manner (P<0.0001). The rates of apoptosis in the KM12SM (P=0.001) and KM12L4a cell lines (P=0.01) were increased time-dependently, though there was no such change in the KM12C cells. The expression of topoisomerase I protein was decreased in each cell line tested and the expression of Bax protein was increased, especially in KM12L4a. In conclusion, the effect of SN-38 on the colon cancer cell lines was mediated via conducting S-phase and G2 arrest and apoptosis. This effect was found in the cell lines with higher metastatic potentials, indicating that SN-38 can be used to treat advanced colon cancers.

  • 316.
    Waltersson, MA
    et al.
    Karolinska University Hospital.
    Karlsson, E
    Karolinska University Hospital.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Fornander, T
    Karolinska University Hospital.
    Skoog, L
    Karolinska University Hospital.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    miR-206 Expression Is Downregulated in Cyclin D1 Amplified Breast Tumours. in CANCER RESEARCH, vol 69, issue 24, pp 579S-579S2009Inngår i: CANCER RESEARCH, 2009, Vol. 69, nr 24, s. 579S-579SKonferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 317.
    Wang, Chao-Jie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Frånbergh-Karlson, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Wang, Da-Wei
    The Third Hospital of Hebei Medical University, China.
    Arbman, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Zhang, Hong
    Örebro University, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Clinicopathological significance of BTF3 expression in colorectal cancer2013Inngår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 34, nr 4, s. 2141-2146Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Basic transcription factor 3 (BTF3) is a general RNA polymerase II transcription factor and is also involved in apoptosis regulation. Increasing evidence shows that BTF3 is aberrantly expressed in several kinds of malignancies, but there is no study to analyze BTF3 expression in colorectal cancer (CRC) patients. Applying immunohistochemistry, we detected BTF3 in CRCs (n = 156), the corresponding distant (n = 42), adjacent normal mucosa (n = 96), lymph node metastases (n  = 35), and analyzed its relationships with clinicopathological and biological variables. Our results showed that BTF3 staining significantly increased from distant or adjacent normal mucosa to primary CRCs (p < 0.0001) or metastases (p = 0.002 and p < 0.0001). BTF3 was higher in distal cancers than in proximal cancers (57 % vs. 39 %, p = 0.041). It also showed stronger staining in primary CRCs stage I and II than that in stage III and IV (64 % vs. 35 %, p = 0.0004), or metastases (64 % vs. 29 %, p = 0.004). Cancers with better differentiation had a higher expression than those with worse differentiation (56 % vs. 37 %, p  = 0.031). There were positive correlations of BTF3 expression with nuclear factor kappa B (NF-κB), RAD50, MRE11, NBS1, and AEG-1 (p  < 0.05). In conclusion, BTF3 overexpression may be an early event in CRC development and could be useful biomarker for the early stage of CRCs. BTF3 has positive correlations with NF-κB, RAD50, MRE11, NBS1 and AEG-1, and might influence complex signal pathways in CRC.

  • 318.
    Wang, Chaojie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Stratmann, Johannes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Zhou, Zong-Guang
    Sichuan University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Suppression of microRNA-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells2010Inngår i: BMC CANCER, ISSN 1471-2407, Vol. 10, nr 616Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: MicroRNAs (miRNAs) are endogenously expressed noncoding RNAs with important biological and pathological functions. Although several studies have shown that microRNA-31 (miR-31) is obviously up-regulated in colorectal cancer (CRC), there is no study on the functional roles of miR-31 in CRC. Methods: Anti-miR (TM) miRNA 31 inhibitor (anti-miR-31) is a sequence-specific and chemically modified oligonucleotide to specifically target and knockdown miR-31 molecule. The effect of anti-miR-31 transfection was investigated by real-time PCR. HCT-116(p53+/+) and HCT-116(p53-/-)colon cancer cells were treated by anti-miR-31 with or without 5-fluorouracil (5-FU), cell proliferation was determined by MTT assay; apoptosis was detected by DAPI staining; cell cycle was evaluated by flow cytometry; colony formation, migration and invasion assays were performed to investigate the effect of suppression of miR-31 on the cell lines. Results: Real-time PCR results showed that anti-miR-31 was efficiently introduced into the cells and reduced miR-31 levels to 44.1% in HCT-116(p53+/+) and 67.8% in HCT-116p(53-/-)cell line (p = 0.042 and 0.046). MTT results showed that anti-miR-31 alone had no effect on the proliferation of HCT-116(p53+/+) or HCT-116(p53-/-). However, when combined with 5-FU, anti-miR-31 inhibited the proliferation of the two cell lines as early as 24 h after exposure to 5-FU (p = 0.038 and 0.044). Suppression of miR-31 caused a reduction of the migratory cells by nearly 50% compared with the negative control in both HCT-116(p53+/+) and HCT-116(p53-/-)(p = 0.040 and 0.001). The invasive ability of the cells were increased by 8-fold in HCT-116(p53+/+) and 2-fold in HCT-116(p53-/-)(p = 0.045 and 0.009). Suppression of miR-31 had no effect on cell cycle and colony formation (p andgt; 0.05). Conclusions: Suppression of miR-31 increases sensitivity to 5-FU at an early stage, and affects cell migration and invasion in HCT-116 colon cancer cells.

  • 319.
    Wang, Chao-Jie
    et al.
    Sichuan University, Institute Digest Surg, Department Colorectal Surg, W China Hospital, Chengdu 610064, Peoples R China Sichuan University, State Key Lab Biotherapy, W China Hospital, Chengdu 610064, Peoples R China .
    Zhou, Zong-Guang
    Sichuan University, Institute Digest Surg, Department Colorectal Surg, W China Hospital, Chengdu 610064, Peoples R China Sichuan University, State Key Lab Biotherapy, W China Hospital, Chengdu 610064, Peoples R China .
    Holmqvist, Annica
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Zhang, Hong
    University Skovde, Div Biomed, Sch Life Science, Skovde, Sweden .
    Li, Yuan
    Sichuan University, Institute Digest Surg, Department Colorectal Surg, W China Hospital, Chengdu 610064, Peoples R China Sichuan University, State Key Lab Biotherapy, W China Hospital, Chengdu 610064, Peoples R China .
    Adell, Gunnar
    Karolinska University Hospital, Department Oncol, Stockholm, Sweden .
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Survivin Expression Quantified by Image Pro-plus Compared With Visual Assessment2009Inngår i: APPLIED IMMUNOHISTOCHEMISTRY and MOLECULAR MORPHOLOGY, ISSN 1062-3345, Vol. 17, nr 6, s. 530-535Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Over the past decades, immunohistochemistry has gained significance and already taken a crucial position in diagnosis of diseases and prognosis of patients. However, manual interpretation of immunohistochemistry and reproducibility of the scoring systems can be highly Subjective. In the article, the immunohistochemical staining of survivin in 98 rectal cancers was analyzed by using Image Pro-Plus (IPP) [3 parameters: density mean, area sum, and integrated optical density (IOD)] and the results were compared with visual assessment (2 parameters: intensity and percentage). The correlations between the 2 methods were examined, significant correlations were observed between density mean and staining intensity (Spearman correlation coefficient, r(s) = 0.806, P andlt; 0.001) IOD and staining intensity (r(s) = 0.9147 P andlt; 0.001) area sum and staining percentage (r(s) = 0.883, P andlt; 0.001), IOD and staining percentage (r(s) = 0.884, P andlt; 0.001). There was no significant difference between survivin expression and clinicopathologic variables (P andgt; 0.05) by visual assessment. However, by IPP analysis, both the density mean and IOD were higher in better-differentiated cancers than in worse differentiated ones (P = 0.02 and 0.03). There was a substantial agreement between the 2 methods. Density mean and IOD of IPP were representative parameters to assess the immunostaining quantification, and increased sensitivity in scoring and provided a more reliable and reproducible analysis of protein expression, especially, more information of the protein expression in relation to clinicopathologic variables can be provided by IPP analysis.

  • 320.
    Wang, Chao-Jie
    et al.
    Sichuan University.
    Zhou, Zong-Guang
    Sichuan University.
    Wang, Ling
    Sichuan University.
    Yang, Lie
    Sichuan University.
    Zhou, Bin
    Sichuan University.
    Gu, Jun
    Sichuan University.
    Chen, Hong-Ying
    Sichuan University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer2009Inngår i: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 26, nr 1, s. 27-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We are just beginning to understand how microRNAs (miRNAs) are involved in tumor-related processes in humans. Applying real-time RT-PCR, we investigated the miR-31, miR-143 and miR-145 expression in 98 primary CRC specimens, along with the corresponding normal mucosa specimens, and analyze the relationship of their expression with clinicopathological features. Our results showed the miR-31 expression was up-regulated in CRC compared to normal mucosa (p = 0.001). Furthermore, miR-31 expression was positively related to advanced TNM stage (p = 0.026) and deeper invasion of tumors (p = 0.024). MiR-145 was down-regulated in both colon (p = 0.001) and rectal (p = 0.012) cancer. MiR-143 was only down-regulated in colon cancer (p = 0.023) but not in rectal cancer (p = 0.351). There was no relationship of miR-143 and miR-145 expression with other clinicopathological features (p > 0.05), except that the miR-145 expression was related to cancer site (p = 0.03). In conclusion, the miR-31 overexpression may be involved in the development and progression of CRC. The miR-143 and miR-145 may play a certain role in the development of colon and/or rectal cancers but not in progression of the disease.

  • 321.
    Wang, Da-Wei
    et al.
    University Skovde.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Adell, Gunnar
    Karolinska University Hospital.
    Mahmoudi, Salah
    Karolinska Institute.
    Farnebo, Marianne
    Karolinska Institute.
    Zhang, Hong
    University of Skovde.
    Wrap53 is an independent prognostic factor in rectal cancer - a study on Swedish rectal cancer trial in INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, vol 26, issue , pp S9-S92010Inngår i: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Spandidos Publications , 2010, Vol. 26, s. S9-S9Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 322.
    Wang, Ming-Wei
    et al.
    Hebei Med Univ, Hosp 1, Dept Neurol, Shijiazhuang, Hebei, Peoples R China.
    Gu, Ping
    Hebei Med Univ, Hosp 1, Dept Neurol, Shijiazhuang, Hebei, Peoples R China.
    Zhang, Zhi-Yong
    Tangshan Gongren Hosp, Dept Pathol, Tangshan, Hebei, Peoples R China.
    Zhu, Zhen-Long
    Hebei Med Univ, Hosp 1, Dept Pathol, Shijiazhuang, Hebei, Peoples R China.
    Geng, Yuan
    Hebei Med Univ, Hosp 1, Dept Neurol, Shijiazhuang, Hebei, Peoples R China.
    Kayed, Hany
    Univ Heidelberg, Univ Hosp Mannheim, Inst Clin Radiol and Nucl Med, Heidelberg, Germany.
    Zentgraf, Hanswalter
    German Canc Res Ctr, D-6900 Heidelberg, Germany.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    FXYD3 Expression in Gliomas and its Clinicopathological Significance2009Inngår i: Oncology Research, ISSN 0965-0407, E-ISSN 1555-3906, Vol. 18, nr 4, s. 133-139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    FXYD3, interacting with Na+/K+-ATPase, is considered a cell surface regulator modulating the function of ion pumps and ion channels. The FXYD3 gene was originally cloned from murine mammary tumors and then from human breast tumors. However, no study of FXYD3 has been carried out in gliomas; therefore, we examined FXYD3 expression in gliomas and its clinicopathological significance. FXYD3 expression was immunohistochemically examined in 71 primary gliomas, along with 37 matched adjacent normal brain samples and 8 recurred gliomas. The frequency of strong FXYD3 expression was higher in the primary tumors in either unmatched (p = 0.046) or matched cases (p = 0.02), compared to normal brain tissue. FXYD3 expression was significantly more increased in females than males (p = 0.01), and in multiple site gliomas than single sites (p = 0.02). There was no difference of FXYD3 expression regarding age, tumor location, size, histological type, and tumor grade (p greater than 0.05). The results suggest that FXYD3 expression may be involved in glioma development, especially in multiple gliomas and female patients.

  • 323.
    Wang, Mo-Jin
    et al.
    Sichuan University, China.
    Li, Yuan
    Sichuan University, China.
    Wang, Rui
    Sichuan University, China.
    Wang, Cun
    Sichuan University, China.
    Yu, Yong-Yang
    Sichuan University, China.
    Yang, Lie
    Sichuan University, China.
    Zhang, Yi
    Sichuan University, China.
    Zhou, Bin
    Sichuan University, China.
    Zhou, Zong-Guang
    Sichuan University, China.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer2013Inngår i: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 28, nr 2, s. 183-189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    Recently, microRNA-124 (miR-124) has been demonstrated as a potential tumor suppressor in several types of cancers. However, the role of miR-124 in colorectal cancer remains unclear. This study was aimed at investigating the clinicopathological significance of miR-124 expression in colorectal cancer.

    Methods

    Quantitative real-time PCR was used to analyze miR-124 expression in 96 colorectal cancers and individual-matched normal mucosa samples. The expression of miR-124 was assessed for associations with clinicopathological characteristics using chi-square test. The survival curves were calculated by the Kaplan–Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis.

    Results

    The miR-124 expression was significantly downregulated in colorectal cancer compared to normal mucosa (P = 0.001). In colorectal cancer, miR-124 decreased expression correlated significantly with the grade of differentiation (P  = 0.021). Univariate survival analysis showed that the downregulated miR-124 was significantly correlated with worse prognosis, both in terms of overall survival (P = 0.017) and disease-free survival (DFS) (P  = 0.014). Further, the downregulated miR-124 was demonstrated as a prognostic factor for overall survival (hazard ratio, HR = 4.634; 95 % confidence interval, CI, 1.731–12.404; P = 0.002) and DFS (HR = 4.533, 95 % CI 1.733–11.856, P = 0.002), independently of gender, age, location, maximum tumor size, depth of invasion, differentiation, and TNM stage.

    Conclusions

    MiR-124 may play a certain role in the development of colorectal cancer. The downregulation expression of miR-124 is an independent prognostic factor in patients with colorectal cancer.

  • 324.
    Wang, Mojin
    et al.
    Sichuan University, Peoples R China.
    Zhang, Peng
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China .
    Liu, Guanghui
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Zhan, Lan
    Sichuan University, Peoples R China.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    The quantitative analysis by stem-loop real-time PCR revealed the microRNA-34a, microRNA-155 and microRNA-200c overexpression in human colorectal cancer2012Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, nr 5, s. 3113-3118Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The recently identified class of microRNAs (miRNAs) provided a new insight in cancer research. As the member of miRNAs family, miR-34a, miR-155 and miR-200c abnormalities have been found in various types of cancer. However, the relationship between these three miRNAs (miR-34a, miR-155 and miR-200c) and colorectal cancer is unclear. In this study, we applied stem-loop real-time PCR to quantitatively detect miR-34a, miR-155 and miR-200c expression in 109 pair-matched human colorectal cancers and the corresponding normal mucosa. MiR-34a (2.2-fold), miR-155 (2.3-fold) and miR-200c (3.1-fold) were all expressed at higher levels in colorectal cancer (P = 0.001, 0.005 and 0.001, respectively). In rectum, miR-34a and miR-200c were significantly upregulated (P = 0.006 and 0.007), while the miR-155 overexpression was not statistically significant (P = 0.083). In colon, the higher expression of three miRNAs was seen, however, without significant difference (P andgt; 0.05). We also found that the miR-34a expression was higher in rectal cancer having more advanced TNM stage (III + IV, P = 0.03). Then miR-200c expression was positively correlated with and sera CEA level of rectal cancer patients (P = 0.04). In conclusion, our results thus suggest that the overexpression of miR-34a, miR-155 and miR-200c be associated with the development of colorectal cancer, meanwhile miR-34a may be involved in the development and progression of rectal cancer. The more deeply and larger scale research are required to prove the correlation.

  • 325.
    Wang, Mo-Jin
    et al.
    Sichuan University.
    Zhou, Zong-Guang
    Sichuan University.
    Wang, Ling
    Sichuan University.
    Yu, Yong-Yang
    Sichuan University.
    Zhang, Peng
    Sichuan University.
    Zhang, Yi
    Sichuan University.
    Cui, Chang-Fu
    Sichuan University.
    Yang, Lie
    Sichuan University.
    Li, Yuan
    Sichuan University.
    Zhou, Bin
    Sichuan University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    The Ile646Val (2073A > G) Polymorphism in the Kinase-Binding Domain of A-Kinase Anchoring Protein 10 and the Risk of Colorectal Cancer2009Inngår i: ONCOLOGY, ISSN 0030-2414, Vol. 76, nr 3, s. 199-204Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The purpose of this study is to investigate whether the Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) is related to the risk of colorectal cancer (CRC), clinicopathological variables and the environmental factors for the development of CRC. Methods: Applying TaqMan allelic discrimination, we investigated AKAP10 Ile646Val (2073A>G) polymorphism in 288 Chinese CRC patients and 281 healthy controls. Results: Logistic regression analysis revealed a significant association of AKAP10 Ile646Val (2073A>G) polymorphism with increased CRC risk (adjusted OR = 1.44, 95% CI 1.01-2.07, p = 0.02). Stratification analysis showed that the increased risk associated with the variant genotypes (GG+AG) was more evident in male subjects (adjusted OR = 1.48, 95% CI 0.94-2.34, p = 0.03). Compared with the AA genotype, the adjusted OR for the variant genotypes was 1.81 (95% CI 1.08 - 3.05, p = 0.01) among young subjects (age ! 57 years). Among individuals who did not smoke or who smoked lightly, there was a significantly increased risk with the variant genotypes (adjusted OR = 1.66, 95% CI 1.08 - 2.56, p = 0.02). We did not observe a relationship between the AKAP10 polymorphism and other clinicopathological and environmental factors. Conclusions: Our data suggested that the AKAP10 2073A>G variation is associated with an increased risk of CRC in the Chinese population.

  • 326.
    Wang, Yong
    et al.
    Sichuan University.
    Li, Yuan
    Sichuan University.
    Zhang, Wen-Yan
    Sichuan University.
    Xia, Qing-Jie
    Sichuan University.
    Li, Hong-Guang
    Sichuan University.
    Wang, Rong
    Sichuan University.
    Yang, Lie
    Sichuan University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Zhou, Zong-Guang
    Sichuan University.
    mRNA expression of minichromosome maintenance 2 in colonic adenoma and adenocarcinoma2009Inngår i: EUROPEAN JOURNAL OF CANCER PREVENTION, ISSN 0959-8278, Vol. 18, nr 1, s. 40-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    As proliferation is essential for Progression from normal cells to tumor, certain markers specific to proliferating cells may permit detection of premalignant lesions. Here, we aimed to evaluate the possible value of a proliferation marker, minichromosome maintenance 2 (MCM2), in the early diagnosis of colorectal cancer, by analyzing the difference in MCM2 expression among normal mucosa, adenoma, and adenocarcinoma, and investigating the relationship of MCM2 expression in adenomas with clinicopathologic variables. Using immunohistochemistry and real-time reverse transcription-PCR, we observed that the expression of MCM2 protein was present on basal third to half of colonic crypts in normal mucosa, whereas throughout the epithelium in adenomas and adenocarcinomas, the expression of MCM2 mRNA in adenocarcinomas was significantly higher than in adenomas (P=0.001), whereas the difference between adenoma and normal mucosa was not significant (P=0.184); we also found that the expression of MCM2 mRNA tended to be increased in the adenomas with high-grade dysplasia, or in older patients, respectively, compared with those with low-grade dysplasia, and younger patients. These results suggested the potential value of MCM2 in early diagnosis of colorectal cancer.

  • 327.
    Wegman Palmebäck, Pia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Elingarami, Sauli
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Wingren, Sten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal breast cancer patients2007Inngår i: Breast Cancer Research, ISSN 1465-5411, Vol. 9, nr 1, s. R7-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction

    Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer. Even if most patients benefit from tamoxifen, many breast tumours either fail to respond or become resistant. Because tamoxifen is extensively metabolised by polymorphic enzymes, one proposed mechanism underlying the resistance is altered metabolism. In the present study we investigated the prognostic and/or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 (*3), CYP2D6 (*4), sulphotransferase 1A1 (SULT1A1; *2) and UDP-glucuronosyltransferase 2B15 (UGT2B15; *2) in tamoxifen-treated patients with breast cancer.

    Methods

    In all, 677 tamoxifen-treated postmenopausal patients with breast cancer, of whom 238 were randomised to either 2 or 5 years of tamoxifen, were genotyped by using PCR with restriction fragment length polymorphism or PCR with denaturing high-performance liquid chromatography.

    Results

    The prognostic evaluation performed in the total population revealed a significantly better disease-free survival in patients homozygous for CYP2D6*4. For CYP3A5, SULT1A1 and UGT2B15 no prognostic significance was observed. In the randomised group we found that for CYP3A5, homozygous carriers of the *3 allele tended to have an increased risk of recurrence when treated for 2 years with tamoxifen, although this was not statistically significant (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 0.68 to 11.99, P = 0.15). In the group randomised to 5 years' tamoxifen the survival pattern shifted towards a significantly improved recurrence-free survival (RFS) among CYP3A5*3-homozygous patients (HR = 0.20, 95% CI = 0.07 to 0.55, P = 0.002). No reliable differences could be seen between treatment duration and the genotypes of CYP2D6, SULT1A1 or UGT2B15. The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5*3 homozygotes was also seen in a multivariate Cox model (HR = 0.13, CI = 0.02 to 0.86, P = 0.03), whereas no differences could be seen for CYP2D6, SULT1A1 and UGT2B15.

    Conclusion

    The metabolism of tamoxifen is complex and the mechanisms responsible for the resistance are unlikely to be explained by a single polymorphism; instead it is a combination of several mechanisms. However, the present data suggest that genetic variation in CYP3A5 may predict response to tamoxifen therapy.

  • 328.
    Wegman (Palmebäck), Pia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Rutqvist, Lars-Erik
    Department of Oncology, Huddinge University Hospital, Stockholm, Sweden.
    Wingren, Sten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    p53 polymorphic variants at codon 72 and the outcome of therapy in randomized breast cancer patients2006Inngår i: Pharmacogenetics and Genomics, ISSN 1744-6872, Vol. 16, nr 5, s. 347-351Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Adjuvant therapy of breast cancer patients reduces the risk of recurrence and mortality, although, a substantial proportion of patients acquire resistance and relapse in the disease. Predictors of therapeutic response are therefore important to avoid both therapy resistance and the side effects of inefficient regimes. The p53 protein is a key determinant to induce either growth arrest or apoptosis in response to cytotoxic stress.

     

    Methods: In the search for predictive markers of cancer therapy we investigated a common Arg72/Pro72 polymorphism in the p53 gene, which has been shown to influence the apoptotic potential. Using PCR and RFLP we genotyped 220 breast cancer patients randomized to radiotherapy versus chemotherapy and tamoxifen versus no tamoxifen.

     

    Results: Oestrogen-receptor positive patients possessing at least one Pro72 allele had better distant recurrence-free survival when randomized to tamoxifen compared to those who were not (P=0.0033), as also demonstrated by the significantly decreased hazard ratio (HR=0.28, 95% CI 0.12–0.65). Among patients homozygous for the Arg72 genotype the outcome was approximately equal between tamoxifen treated and non-tamoxifen treated patients (P=0.65). When the calculated hazard ratios for the genotypes were compared by an interaction test a significant difference was found (P=0.0088).

     

    Conclusion: The present report indicates that the codon 72 polymorphism in the p53 gene may be a predictor of tamoxifen response, suggesting that breast cancer patients lacking the Pro72 allele might be candidates for other therapies.

  • 329.
    Wegman (Palmebäck), Pia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Vainikka, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Skoog, Lambert
    Division of Cytology, Karolinska Hospital, Stockholm, Sweden.
    Rutqvist, Lars-Erik
    Department of Oncology, Huddinge University Hospital, Stockholm, Sweden.
    Wingren, Sten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients2005Inngår i: Breast Cancer Research, ISSN 1465-5411, Vol. 7, nr 3, s. R284-R290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy.

    Methods

    The patients were genotyped using PCR followed by cleavage with restriction enzymes.

    Results

    Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041).

    Conclusion

    The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort.

  • 330.
    Wegman, Pia
    et al.
    University Orebro, Sch Hlth and Med Science, Department Clin Med, S-70185 Orebro, Sweden .
    Gothlin Eremo, Anna
    University Orebro, Sch Hlth and Med Science, Department Clin Med, S-70185 Orebro, Sweden .
    Lindlof, Angelica
    Skovde University, Sch Life Science, Syst Biol Research Centre, S-54145 Skovde, Sweden .
    Karlsson, Mats
    Orebro University Hospital, Sch Hlth and Med Science, Department Pathol, S-70185 Orebro, Sweden .
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Wingren, Sten
    University Orebro, Sch Hlth and Med Science, Department Clin Med, S-70185 Orebro, Sweden .
    Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen2011Inngår i: INTERNATIONAL JOURNAL OF ONCOLOGY, ISSN 1019-6439, Vol. 38, nr 4, s. 1145-1151Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aromatase is an important enzyme in the local synthesis of oestrogens and its expression has been shown to be increased in breast cancer through the activation of multiple promoters. However, the mechanisms behind this are not yet fully understood. A novel candidate in this context is the transcription factor forkhead box L2 (FOXL2), which has been recognised to be co-expressed with aromatase and transcriptionally active promoter 11 in developing goat and chicken ovaries. We propose that FOXL2 could be involved in the increased expression of aromatase in breast cancer. We examined FOXL2 and its relation to aromatase in 132 postmenopausal breast cancer patients by immunohistochemistry. Using in silico analysis, we further searched for FOXL2 binding-elements in the aromatase gene promoters. The results demonstrate that FOXL2 is expressed in breast cancer and influences clinical outcome with improved recurrence-free survival in cases with nuclear expression. In a multivariate Cox model, nuclear FOXL2 was a significant prognostic factor in ER-positive patients treated with tamoxifen (HR=0.18, 95% confidence interval (CI)=0.04-0.81, P=0.03). Tumours expressing nuclear FOXL2 were also more likely positive for stromal and/or cytoplasmic aromatase (P=0.03 and P=0.008, respectively). In silico analyses revealed binding elements of FOXL2 in promoters 1.3, 11 and 17 of the aromatase gene of which promoter 1.7 was most significant. In conclusion, this is the first study to report that FOXL2 is expressed in breast cancer and correlates with aromatase as well as with clinical outcome. The results further strengthen a possible binding of FOXL2 to aromatase promoter 1.7. Nevertheless, whether FOXL2 is a direct activator of aromatase requires further investigation.

  • 331.
    Weiner, Maria
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Skoog, L
    Karolinska Institute, Sweden.
    Fornander, T
    Karolinska Institute, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Sgroi, D C.
    Massachusetts General Hospital, Boston, USA.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Oestrogen receptor co-activator AIB1 is a marker of tamoxifen benefit in postmenopausal breast cancer2013Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, nr 8, s. 1994-1999Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The oestrogen receptor (ER) co-activator amplified in breast cancer 1 (AIB1) has been suggested as a treatment predictive and prognostic marker in breast cancer. Studies have however not been unanimous.

    Patients and methods AIB1 protein expression was analysed by immunohistochemistry on tissue micro-arrays with tumour samples from 910 postmenopausal women randomised to tamoxifen treatment or no adjuvant treatment. Associations between AIB1 expression, clinical outcome in the two arms and other clinicopathological variables were examined.

    Results In patients with ER-positive breast cancer expressing low tumour levels of AIB1 (<75%), we found no significant difference in recurrence-free survival (RFS) or breast cancer-specific survival (BCS) between tamoxifen treated and untreated patients. In patients with high AIB1 expression (>75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26–0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21–0.69, P = 0.0015) with tamoxifen treatment. In the untreated arm, we found high expression of AIB1 to be significantly associated with lower RFS (HR 1.74, 95% CI 1.20–2.53, P = 0.0038).

    Conclusion Our results suggest that high AIB1 is a predictive marker of good response to tamoxifen treatment in postmenopausal women and a prognostic marker of decreased RFS in systemically untreated patients.

  • 332.
    Welander, Jenny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Garvin, Stina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Bohnmark, Rickard
    Cty Council Ostergotland, Dept Radiol, SE-58185 Linkoping, Sweden .
    Isaksson, Lars
    Cty Council Ostergotland, Dept Vasc Surg, SE-58185 Linkoping, Sweden .
    Wiseman, Roger W.
    University of Wisconsin, WI USA .
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Gimm, Oliver
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Editorial Material: Germline SDHA Mutation Detected by Next-Generation Sequencing in a Young Index Patient With Large Paraganglioma2013Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, nr 8, s. E1379-E1380Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 333.
    Widegren, Emma
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Önnesjö, Sofia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Arbman, Gunnar
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Kirurgiska kliniken i Östergötland med verksamhet i Linköping, Norrköping och Motala.
    Kayed, Hany
    Univ Heidelberg, Inst Clin Radiol and Nucl Med, Univ Hosp Mannheim, Heidelberg, Germany.
    Zentgraf, Hanswalter
    German Canc Res Ctr, D-6900 Heidelberg, Germany.
    Kleeff, Joerg
    Tech Univ Munich, Dept Surg, Munich, Germany.
    Zhang, Hong
    Univ Skovde, Sch Life Sci, Skovde, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Expression of FXYD3 Protein in Relation to Biological and Clinicopathological Variables in Colorectal Cancers2009Inngår i: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 55, nr 6, s. 407-413Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: FXYD3 is up-/down-regulated in different types of cancers. We examined FXYD3 expression in colorectal cancers and its relationship to biological and clinicopathological variables. Patients and Methods: Expression of FXYD3 protein was immunohistochemically examined in distant normal mucosa (n = 34), adjacent normal mucosa (n = 72), primary tumour (n = 150) and lymph node metastasis (n = 35) from colorectal cancer patients. Results: FXYD3 was highly expressed in primary tumour compared to adjacent normal mucosa (p = 0.02). FXYD3 was or tended to be positively related to the expression of ras (p = 0.02), p53 (p = 0.06), legumain (p = 0.02) and proliferating cell nuclear antigen (p = 0.03). Moreover, there was a higher frequency of strong FXYD3 expression in Dukes A-C tumours than in D tumours (p = 0.04). The strong FXYD3 expression tended to predict worse survival in the patients with Dukes A + B tumour (p = 0.07), while there was no such tendency in the patients with Dukes C + D tumour (p = 0.94). The tumours located in the colon had a higher degree of FXYD3 expression than the tumours located in the rectum (p = 0.05). Conclusion: The FXYD3 was associated with certain biological variables and may be involved in the development of the relative earlier stages of colorectal cancers.

  • 334.
    Willander, Kerstin
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    Ungerbäck, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Karlsson, Karin
    Department of Hematology, Lund University Hospital, Lund, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Linderholm, Mats
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia2010Inngår i: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 85, nr 3, s. 251-256Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. OBJECTIVE: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS: A total of 210 patients with B-CLL were followed for up to 19 yr. RESULTS: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. CONCLUSION: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.

  • 335.
    Xu, Bing
    et al.
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Zhou, Zong-Guang
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Li, Yuan
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Wang, Ling
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Yang, Lie
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Zhou, Bin
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Liu, Hai-Li
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Song, Jun-Min
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Zeng, Yu-Jian
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Wang, Rong
    Department of General Surgery West China Hospital, Sichuan University, Chengdu, China.
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Clinicopathological significance of caspase-8 and caspase-10 expression in rectal cancer2008Inngår i: Oncology, ISSN 0890-9091, Vol. 74, nr 3-4, s. 229-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer. Methods: The expression of caspase-8 and -10 was determined by real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal cancers and 93 corresponding normal rectal mucosa samples. Results: Compared with normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p = 0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers (p < 0.001) compared with normal mucosa samples. Cancers with poor differentiation had lower caspase-10 mRNA and protein levels than those with better differentiation (p = 0.041 and p = 0.046, respectively). The protein expression of caspase-8 and -10 was in accordance with the mRNA expression (p = 0.043 and p = 0.018, respectively). Conclusions: Caspase-8 expression was up-regulated in rectal adenomas. Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer. Copyright © 2008 S. Karger AG.

  • 336.
    Yan, BY
    et al.
    Hebei Medical University, Shijiazhuang, China;.
    Wang, DW
    Hebei Medical University, Shijiazhuang, China;.
    Zhu, ZL
    Hebei Medical University, Shijiazhuang, China;.
    Yang, YH
    Hebei Medical University, Shijiazhuang, China;.
    Wang, MW
    Hebei Medical University, Shijiazhuang, China;.
    Cui, DS
    Hebei Medical University, Shijiazhuang, China;.
    Zhang, Hong
    University of Skövde, Skövde, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Overexpression of MAC30 in the Cytoplasm of Oral Squamous Cell Carcinoma Predicts Nodal Metastasis and Poor Differentiation2010Inngår i: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 56, nr 6, s. 424-428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Expression of the meningioma-associated protein (MAC30) was increased in several types of tumors, including esophageal, gastric and colon tumors, compared to normal tissue. MAC30 expression levels gradually increased from normal colorectal mucosa to primary colorectal cancer and colorectal cancer spreading to the lymph nodes. MAC30 expression was related to survival in patients with colorectal cancer. However, there is no study on MAC30 in oral squamous cell carcinoma (OSCC). Methods: Therefore, MAC30 expression in OSCC was investigated and possible associations of MAC30 expression with clinicopathological variables in OSCC have been analyzed. MAC30 expression was immunohistochemically examined in 20 normal oral mucosa and 43 OSCC specimens. Results: Expression levels of MAC30 in the cytoplasm markedly increased from normal oral epithelial cells to primary OSCC. Strong cytoplasmic staining was significantly higher in primary OSCC compared to normal oral mucosa samples (51 vs. 20%, p = 0.019). Furthermore, MAC30 expression levels in primary tumors of patients with lymph node metastasis exceeded levels in those without metastasis (65 vs. 35%, p = 0.048), and MAC30 expression in poorly differentiated tumors was higher than in well-differentiated ones (90 vs. 39%, p = 0.005). Conclusion: Overexpression of MAC30 in the cytoplasm of OSCC may predict nodal metastasis and poor differentiation.

  • 337.
    Yang, Lie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Olsson, Birgit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Pfeifer, Daniella
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, J-I
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Zhou, Z-G
    Sichuan University.
    Jiang, X
    Sichuan University.
    Fredriksson, Bengt-Arne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Zhang, H
    University of Skovde.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Knockdown of peroxisome proliferator-activated receptor-beta induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells2010Inngår i: ONCOGENE, ISSN 0950-9232, Vol. 29, nr 4, s. 516-526Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The role of peroxisome proliferator-activated receptor-beta/delta (PPAR-beta/delta) in the pathogenesis of colon cancer remains highly controversial. This study specifically silenced the PPAR-beta expression in three colon cancer cell lines with different metastatic potentials. Although PPAR-beta knockdown resulted in more malignant morphological changes, bigger colony sizes and lower carcinoembryonic antigen (CEA) secretion, and enhanced the cell-fibronectin adhesion, cell invasion and migration were unaffected. These effects were stronger in poorly metastatic cell lines compared with highly metastatic ones. Simultaneously, PPAR-beta knockdown decreased the mRNAs encoding adipocyte differentiation-related protein and liver fatty acid binding protein, and increased the mRNA of ILK, whereas the mRNAs encoding integrin-beta 1 and angiopoietin-like 4 were unchanged. Using immunohistochemistry, we determined that the intensity of PPAR-beta expression was stronger in rectal cancers with better differentiation than in those with poor differentiation, and was stronger in early-stage tumors than in advanced ones. Together, these findings consistently indicate that PPAR-beta may facilitate differentiation and inhibit the cell-fibronectin adhesion of colon cancer, having a role as an inhibitor in the carcinogenesis and progression of colorectal cancer. Interestingly, PPAR-beta seems to have a more important role in poorly metastatic cells than in highly metastatic ones.

  • 338.
    Yang, Lie
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi.
    Zhang, Hong
    University of Skovde.
    Zhou, Zong-Guang
    Sichuan University.
    Yan, Hui
    Sichuan University.
    Adell, G
    Karolinska University Hospital.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Biological Function and Prognostic Significance of Peroxisome Proliferator-Activated Receptor delta in Rectal Cancer2011Inngår i: CLINICAL CANCER RESEARCH, ISSN 1078-0432, Vol. 17, nr 11, s. 3760-3770Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To investigate the expression significance of PPAR beta/delta in relation to radiotherapy (RT), clinicopathologic, and prognostic variables of rectal cancer patients. Experimental Design: We included 141 primary rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. Tissue microarray samples from the excised rectal cancers and the adjacent or distant normal mucosa and lymph node metastases were stained with PPAR delta antibody. Survival probability was computed by the Kaplan-Meier method and Cox regression model. The proliferation of colon cancer cell lines KM12C, KM12SM, and KM12L4a was assayed after PPAR delta knockdown. Results: PPAR delta was increased from adjacent or distant normal mucosa to primary cancers, whereas it decreased from primary cancers to lymph node metastases. After RT, PPAR delta was increased in normal mucosa, whereas it decreased in primary cancers and lymph node metastases. In primary cancers, the high expression of PPAR delta was related to higher frequency of stage I cases, lower lymph node metastasis rate, and low expression of Ki-67 in the unirradiated cases, and related to favorable survival in the cases either with or without RT. The proliferation of the KM12C, KM12SM, or KM12L4a cells was significantly accelerated after PPAR delta knockdown. Conclusions: RT decreases the PPAR delta expression in primary rectal cancers and lymph node metastases. PPAR delta is related to the early development of rectal cancer and inhibits the proliferation of colorectal cancer cells. Increase of PPAR delta predicts favorable survival in the rectal cancer patients either with or without preoperative

  • 339.
    Yang, Lie
    et al.
    West China Hospital, Sichuan University, China.
    Zhou, Jin
    West China Hospital, Sichuan University, China.
    Ma, Qin
    West China Hospital, Sichuan University, China.
    Wang, Cun
    West China Hospital, Sichuan University, China.
    Chen, Keling
    West China Hospital, Sichuan University, China.
    Meng, Wenjian
    West China Hospital, Sichuan University, China.
    Yu, Yongyang
    West China Hospital, Sichuan University, China.
    Zhou, Zongguang
    West China Hospital, Sichuan University, China.
    Sun, Xiaofeng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Knockdown of PPAR δ Gene Promotes the Growth of Colon Cancer and Reduces the Sensitivity to Bevacizumab in Nude Mice Model2013Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The role of peroxisome proliferator – activated receptor- δ (PPAR δ) gene in colon carcinogenesis remains highly controversial. Here, we established nude mice xenograft model using a human colon cancer cell line KM12C either with PPAR δ silenced or normal. The xenografts in PPAR δ-silenced group grew significantly larger and heavier with less differentiation, promoted cell proliferation, increased expression of vascular endothelial growth factor (VEGF) and similar apoptosis index compared with those of PPAR δ-normal group. After treated with the specific VEGF inhibitor bevacizumab, the capacities of growth and proliferation of xenografts were decreased in both groups while still significantly higher in PPAR δ-silenced group than in PPAR δ-normal group. Administration of PPAR δ agonist significantly decreased VEGF expression in PPAR δ-normal KM12C cells but not in PPAR δ-silenced cells. These findings demonstrate that, knockdown of PPAR δ promotes the growth of colon cancer by inducing less differentiation, accelerating the proliferation and VEGF expression of tumor cells in vivo, and reduces tumor sensitivity to bevacizumab. This study indicates that PPAR δ attenuates colon carcinogenesis.

  • 340.
    Zervas, K.
    et al.
    Theagene Anticancer Hospital.
    Katodritou, E.
    Theagen Cancer Centre.
    Delforge, M.
    University Hospital Leuven.
    de Samblanx, H.
    ZNA Middelheim.
    Sargin, D.
    Istanbul University.
    Hulin, C.
    University Nancy Brabois.
    Ahlberg, Lucia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Hematologiska kliniken US.
    de la Rubia, J.
    Hospital La Fe.
    Abdulkadyrov, K.
    Russian Science Research Institute.
    Ganguly, R.
    Johnson & Johnson Pharmaceutical.
    Diels, J.
    Johnson & Johnson Pharmaceutical.
    Dhawan, R.
    Johnson & Johnson Pharmaceutical.
    PATIENT RESPONSE TO BORTEZOMIB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: INTERIM RESULTS FROM AN OBSERVATIONAL STUDY2009Inngår i: in HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, vol 94, 2009, Vol. 94, s. 1591-Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 341.
    Zhang, Hong
    et al.
    University of Skovde, Sweden .
    Wang, Da-Wei
    University of Skovde, Sweden Hebei Medical University, Peoples R China .
    Adell, Gunnar
    Karolinska University Hospital, Sweden .
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    WRAP53 is an independent prognostic factor in rectal cancer- a study of Swedish clinical trial of preoperative radiotherapy in rectal cancer patients2012Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, nr 294Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Expression of WRAP53 protein has oncogenic properties and it is up regulated in several types of tumors. less thanbrgreater than less thanbrgreater thanMethods: We examined expression of WRAP53 protein in rectal cancers and analyzed its relationship to the response to preoperative radiotherapy and patient survival. The WRAP53 protein was examined by immunohistochemistry in normal mucosa, primary tumors and lymph node metastases from 143 rectal cancer patients participated in a Swedish clinical trial of preoperative radiotherapy. less thanbrgreater than less thanbrgreater thanResults: Frequency of WRAP53 protein expression was increased in primary rectal cancer compared to the normal mucosa (p andlt; 0.05). In non-radiotherapy group positive WRAP53 in primary tumors (p = 0.03, RR, 3.73, 95% CI, 1.13-11.89) or metastases (p = 0.01, RR, 4.11, 95% CI, 1.25-13.14), was associated with poor prognosis independently of stages and differentiations. In radiotherapy group, positive WRAP53 in the metastasis correlated with better survival (p = 0.04). An interaction analysis showed that the correlations of WRAP53 with the prognostic significance with and without radiotherapy in the metastasis differed (p = 0.01). In the radiotherapy group, expression of WRAP53 in metastases gave a better outcome (p = 0.02, RR, 0.32, 95% CI, 0.13-0.84), and an interaction analysis showed significance between the two groups (p = 0.01). less thanbrgreater than less thanbrgreater thanConclusion: WRAP53 may be a new biomarker used to predict prognosis and to select suitable patients for preoperative radiotherapy.

  • 342.
    Zhang, Hong
    et al.
    University of Skovde.
    Widegren, Emma
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi.
    Wang, Da-Wei
    University of Skovde.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    SPARCL1: a potential molecule associated with tumor diagnosis, progression and prognosis of colorectal cancer2011Inngår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 32, nr 6, s. 1225-1231Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated whether SPARCL1 played an essential role in tumor initiation, formation and progression of colorectal carcinomas. In this study, we examined expression of SPARCL1 protein in the normal colorectal mucosa, adjacent normal mucosa and primary and lymph node metastases from colorectal cancer patients. In matched patients, we found that SPARCL1 was negative in the distant normal colorectal mucosa, weakly expressed in the adjacent normal mucosa, strongly expressed in primary colorectal adenocarcinomas and slightly expressed in their lymph node metastases. A similar pattern was observed in the SPARCL1 expression from our series of non-matched colorectal cancer patients. The strongest expression and highest frequency of the SPARCL1 protein were found in the primary cancers. Interestingly, in the primary tumors, the frequency of SPARCL1 expression was significantly increased from the Dukes A to Dukes B tumors and then decreased gradually from the Dukes B to C and D tumors. There was no difference in the intensity of SPARCL1 expression between the central areas and invasion margins of the primary tumors. Moreover, the SPARCL1 protein was more strongly expressed in the highly differentiated tumors than the lower differentiated ones. The patients with positive expression of SPARCL1 in their tumors had worse prognosis than the patients with SPARCL1-negative ones, even after the analyses by Multivariate and Interaction method. Expression of SPARCL1 protein might be a valuable biomarker for early diagnosis in colorectal cancers and further predicting patients prognosis.

  • 343.
    Zhang, Hong-Zhen
    et al.
    Hebei Medical University.
    Li, Xue-Hui
    Hebei Medical University.
    Zhang, Xia
    Hebei Medical University.
    Zhang, Zhi-Yong
    Tangshan Gongren Hospital.
    Meng, Ya-Li
    Hebei Medical University.
    Xu, Shu-Wen
    Hebei Medical University.
    Zheng, Yan
    Hebei Medical University.
    Zhu, Zhen-Long
    Hebei Medical University.
    Cui, Dong-Sheng
    Hebei Medical University.
    Huang, Li-Xia
    Hebei Medical University.
    Yan, Bao-Yong
    Hebei Medical University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    PINCH Protein Expression in Normal Endometrium, Atypical Endometrial Hyperplasia and Endometrioid Endometrial Carcinoma2010Inngår i: CHEMOTHERAPY, ISSN 0009-3157, Vol. 56, nr 4, s. 291-297Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Particularly interesting new cysteine-histidine rich protein ( PINCH), as an adapter protein of the LIM family for signal transduction in the integrin and growth factor pathway, is upregulated in the stroma of several common types of cancers and involved in promoting tumor progression. In the present study, we examined PINCH expression in normal endometrium, atypical endometrial hyperplasia and endometrioid carcinoma, and further studied the relationships of PINCH expression with clinicopathological variables in cancer patients. Methods: PINCH expression was examined by immunohistochemistry in 23 normal endometrial samples, 18 atypical endometrial hyperplasias and 48 endometrioid endometrial carcinomas. Results: The PINCH expression in the stroma of cancer (71%) was significantly increased compared to either normal endometrium (17%, p andlt; 0.0001) or atypical hyperplasia (39%, p = 0.017), along with 9 cancers that had stronger PINCH expressions at the invasive margin of the cancers compared to the inner cancers. PINCH expression in cancer was higher in the patients with hypertension (p = 0.041) and estrogen exposure time andgt;30 years (p = 0.021). On the other hand, PINCH expression was not related to menopausal status, gravid status, blood sugar/lipid, family background of cancer, histological grade, myometrial invasion, cervical involvement, lymph nodal metastases, growth pattern, estrogen and progestogen receptors (p andgt; 0.05). Conclusion: The results suggest that PINCH seems to play a role, presently unknown, in the tumorigenesis and development of endometrial cancer that merits further study.

  • 344.
    Zhang, Jin-Ting
    et al.
    Department of Stomatology Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Wang, Da-Wei
    Department of Stomatology Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Li, Qing-Xing
    Department of Stomatology Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Zhu, Zhen-Long
    Department of Pathology Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Wang, Ming-Wei
    Central Laboratory Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Cui, Dong-Sheng
    Central Laboratory Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Yang, Yan-Hong
    Department of Pathology Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Gu, Yu-Xin
    Department of Stomatology Hebei Medical University, Shijiazhuang 050031, Hebei Province, China.
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Nuclear to cytoplasmic shift of p33ING1b protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables2008Inngår i: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 134, nr 3, s. 421-426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: p33ING1b, as a candidate tumour suppressor gene, has been found to be expressed a proportion of oral squamous cell carcinomas (OSCCs), however, its clinicopathological significance is not studied yet. Our aim was to investigate association of p33ING1b expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in OSCCs. Methods: p33ING1b expression was immumohistochemically examined in 20 normal oral mucosa specimens and 49 OSCCs. Results: Normal squamous cells showed only p33ING1b nuclear expression (no cytoplasmic expression), with a rate of 90% positive cases. While 24% of OSCCs appeared cytoplasmic expression (11 of them with weak nuclear staining) and the rest tumours (76%) were negative for p33 ING1b. Furthermore, the cases having lymph node metastasis showed a higher frequency of positive cytoplasmic expression than those without metastasis (P = 0.03). The p33ING1b cytoplasmic expression was positively related to PINCH expression (P = 0.04), the cases positive for both proteins had a high rate of the metastasis (P = 0.03). Conclusions: The transfer of p33ING1b protein from the nucleus to the cytoplasm may result in loss of normal cellular function of the protein, which might play a role in the tumourigenesis and metastasis of OSCCs. © 2007 Springer-Verlag.

  • 345. Zhang, JT
    et al.
    Li, QX
    Wang, DW
    Zhu, ZL
    Yang, YH
    Cui, DS
    Wang, MW
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Up-regulation of PINCH in the stroma of oral squamous cell carcinoma predicts nodal metastasis2005Inngår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 14, nr 6, s. 1519-1522Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Particularly interesting new cysteine-histidine rich protein (PINCH), an adapter protein involved in integrin and growth factor signalling, is up-regulated in the stroma of colorectal, breast, prostate, lung and skin cancer. Strong stromal immunostaining for PINCH is an independent prognostic indicator for reduced survival in colorectal cancer, suggesting that PINCH is involved in the signalling that promotes tumour progression. Since no study on PINCH has been carried out in oral squamous cell carcinoma (OSCC), this study aimed to determine PINCH expression in OSCC and its clinicopathological significance. PINCH protein expression was examined by immunohistochemistry in 20 normal oral mucosa and in 57 OSCC specimens, The frequency of strong PINCH immunostaining was higher in tumour-associated stroma of OSCC (37%) as compared to normal oral mucosa (10%) (p=0.02). Strong PINCH stromal immunostaining predicted nodal metastasis: 19/26 (73%) OSCC cases with nodal metastasis had strong PINCH immunostaining compared to 9/31 (29%) cases without nodal metastasis (p=0.02). The PINCH expression in OSCC was more intense in stroma at the invasive edge than in intratumoural stroma. In conclusion, the up-regulation of PINCH protein in stroma may be involved in promoting invasion and metastasis in OSCC.

  • 346.
    Zhang, Zhi Y
    et al.
    Tangshan Gongren Hospital, China.
    Tian, Yan F
    First Hospital of Hebei Medical University, Shijiazhuang, China .
    Wang, Yuan Y
    First Hospital of Hebei Medical University, Shijiazhuang, China .
    Zhang, Li J
    First Hospital of Hebei Medical University, Shijiazhuang, China .
    Zhao, Zeng R
    First Hospital of Hebei Medical University, Shijiazhuang, China .
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    PINCH mRNA Overexpression in Colorectal Carcinomas Correlated with VEGF and FAS mRNA Expression2011Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 31, nr 12, s. 4127-4133Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Particularly interesting new cysteine-histidine-rich protein (PINCH) was found to be up-regulated in the stroma of colorectal carcinomas (CRCs) in our previous studies and was involved in angiogenesis through activation of fibroblasts in extracellular matrix (ECM) in response to tumors. Here, we examined PINCH mRNA expression in colorectal cancer and investigated its relationship with the clinicopathological features and proliferation cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF) and FAS.

    MATERIALS AND METHODS:

    The primary cancer tissues, adjacent noncancerous tissues and the proximal and distant margins of normal mucosa were collected from 81 colorectal cancer patients during surgery. PINCH, PCNA, VEGF and FAS mRNA expression was examined by reverse transcriptional PCR (RT-PCR).

    RESULTS:

    PINCH mRNA expression was significantly increased in primary tumors compared with that in adjacent noncancerous tissues, and the proximal and distant margins of normal mucosa (p<0.0001). Expression of PINCH mRNA in colon cancer tended to be higher than expression in rectal cancer (p=0.051). Tumors which had infiltrated through the wall of the colorectum trended to have higher PINCH mRNA expression (p=0.073). PINCH mRNA expression in primary tumors was positively related to the expression of PCNA mRNA (r=0.534, p=0.010), VEGF mRNA (r=0.431, p=0.022) and FAS mRNA (r=0.542, p=0.012).

    CONCLUSION:

    PINCH mRNA was overexpressed in colorectal cancer and associated with PCNA mRNA, VEGF mRNA and FAS mRNA expression. PINCH mRNA was involved in the development of colorectal cancer and might play a role in the epithelial mesenchymal transition in the rectum differently than in the colon, through the adenomatous polyposis coli (APC)/catenin pathway.

  • 347.
    Zhang, Zhiyong
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Zhang, Hong
    University of Skovde.
    Adell, Gunnar
    Karolinska University Hospital.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Endosialin expression in relation to clinicopathological and biological variables in rectal cancers with a Swedish clinical trial of preoperative radiotherapy2011Inngår i: BMC CANCER, ISSN 1471-2407, Vol. 11, nr 89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The importance of changes in tumour-associated stroma for tumour initiation and progression has been established. Endosialin is expressed in fibroblasts and pericytes of blood vessels in several types of tumours, and is involved in the progression of colorectal cancer. In order to see whether endosialin was related to radiotherapy (RT) response, and clinicopathological and biological variables, we investigated endosialin expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative RT. Methods: Endosialin was immunohistochemically examined in normal mucosa, including distant (n = 72) and adjacent (n = 112) normal mucosa, and primary tumours (n = 135). Seventy-three of 135 patients received surgery alone and 62 received additional preoperative RT. Results: Endosialin expression in the stroma increased from normal mucosa to tumour (p andlt; 0.0001) both in RT and non-RT group. In the RT group, endosialin expression in the stroma was positively associated with expression of cyclooxygenase-2 (Cox-2) (p = 0.03), p73 (p = 0.01) and phosphates of regenerating liver (PRL) (p = 0.002). Endosialin expression in the tumour cells of both in the RT group (p = 0.01) and the non-RT group (p = 0.06) was observed more often in tumours with an infiltrative growth pattern than in tumours with an expansive growth pattern. In the RT group, endosialin expression in tumour cells was positively related to PRL expression (p = 0.02), whereas in the non-RT group, endosialin expression in tumour cells was positively related to p73 expression (p = 0.01). Conclusions: Endosialin expression may be involved in the progression of rectal cancers, and was related to Cox-2, p73 and PRL expression. However, a direct relationship between endosialin expression and RT responses in patients was not found.

  • 348.
    Zhao, Zeng-Ren
    et al.
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Zhang, Li-Jing
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    He, Xin-Qi
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Zhang, Zhi-Yong
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Zhang, Feng
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Li, Fang
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Pei, Yong-Bin
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Hu, Yue-Ming
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Wang, Ming-Wei
    Hebei Med Univ, Shijiazhuang, Peoples R China.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Significance of mRNA and Protein Expression of MAC30 in Progression of Colorectal Cancer2011Inngår i: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 57, nr 5, s. 394-401Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The aim of our study was to investigate the expression of MAC30 mRNA and its correlation with clinicopathological variables in human colorectal cancer (CRC). Methods: MAC30 mRNA expression was first examined in 55 CRCs, along with the samples from the matched distant normal and adjacent noncancerous tissue by RT-PCR, further verified in 18 CRCs by quantitative RT-PCR. MAC30 protein expression was detected by Western blot in 10 CRCs, and DNA sequencing was performed in 1 case of the paired CRC and the matched noncancerous specimen. MAC30 mRNA expression in two colon cancer cell lines, HCT-116(p53-/-) and HCT-116(p53+/+), was detected by quantitative RT-PCR. Results: The mRNA expression of MAC30 was increased in CRC when compared with distant normal (p < 0.01) and adjacent noncancerous mucosa (p < 0.01). The mean value of MAC30 mRNA expression in the tumor located in the colon was higher than in the rectum (0.677 +/- 0.419 vs. 0.412 +/- 0.162, p = 0.005). As the tumor penetrated the wall of the colon/rectum, MAC30 mRNA expression notably increased in tumors with T3+T4 stage compared to tumors with T1+T2 stage (0.571 +/- 0.364 vs. 0.404 +/- 0.115, p = 0.014). MAC30 protein expression in CRCs was also remarkably elevated compared to the adjacent noncancerous mucosa. There was no mutation in the coding region of the MAC30 gene either in CRC or in the noncancerous mucosa. mRNA expression of p53 was notably decreased in HCT-116(p53-/-) compared to HCT-116(p53+/+), while MAC30 did not vary greatly. Conclusion: The overexpression of MAC30 might be involved in the development and aggressiveness of CRCs, especially in the colon.

  • 349.
    Zhao, Zeng-Ren
    et al.
    Hebei Medical University, Peoples R China Hebei Medical University, Peoples R China .
    Zhang, Li-Jing
    Hebei Medical University, Peoples R China .
    Wang, Yuan-Yuan
    Hebei Medical University, Peoples R China .
    Li, Fang
    Hebei Medical University, Peoples R China .
    Wang, Ming-Wei
    Hebei Medical University, Peoples R China .
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Increased serum level of Nup88 protein is associated with the development of colorectal cancer2012Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, nr 3, s. 1789-1795Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nucleoporin88 (Nup88) has been shown to be overexpressed in a wide variety of malignancies including colorectal cancer (CRC). However, no study about serum Nup88 in human CRC was reported. Therefore, in this study, we investigated the level of serum Nup88 protein and its relationships with clinicopathological variables in CRC. The serum concentration of Nup88 protein was determined by a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) in 118 pre-operative serum samples, 66 post-operative and 96 healthy controls. Among the patients, the levels of CEA (n = 91) and CA19-9 (n = 87) in the pre-operative serum were measured, and DNA sequencing was performed in 12 CRCs and 2 samples from non-cancerous colon tissue. In the same patients, the level of pre-operative serum Nup88 was significantly higher than that of post-operative Nup88 (P = 0.021). Furthermore, the level of pre-operative Nup88 was positively related to the depth of tumor invasion (P = 0.002) and advanced stage (P = 0.001). The level of pre-operative Nup88 in the left colon tended to be higher than that in the right colon and the rectum (P = 0.063). DNA sequencing results showed that there were two single nucleotide polymorphisms, distributed in exon 6 (NM_002532.3:c.1044Gandgt;A (ACG-ACA, Thr -andgt; Thr) and exon 10 (NM_002532.3: c.1389Aandgt;T, CCA-CCT, Pro -andgt; Pro). Serum Nup88 might be a candidate for a new biomarker implicated in the development and aggressiveness of CRCs.

  • 350.
    Zhao, Zeng-Ren
    et al.
    Hebei Medical University.
    Zhang, Zhi-Yong
    Tangshan Gongren Hospital.
    He, Xin-Qi
    Hebei Medical University.
    Hu, Yue-Ming
    Tangshan Gongren Hospital.
    Tian, Yan-Feng
    Hebei Medical University.
    Zhang, Li-Jing
    Hebei Medical University.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Nup88 mRNA overexpression in colorectal cancers and relationship with p532010Inngår i: CANCER BIOMARKERS, ISSN 1574-0153, Vol. 8, nr 2, s. 73-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: We measured nucleoporin 88 (Nup88) mRNA expression in primary colorectal cancers to investigate its relationship with clinicopathological features and p53. Methods: The primary cancer tissues, adjacent noncancerous tissues and the proximal and distant margins of normal mucosa were collected from 73 colorectal cancer patients during surgery. Nup88 mRNA expression was measured on these fresh specimens and on colon cell lines HCT-116 (P53+/+) and HCT-116 (P53-/-) by RT-PCR while p53 mRNA and beta-actin as controls. Nup88 and p53 protein expression were then immunohistochemistrically examined in other 25 colorectal cancers specimens paraffin embedded and formalin fixed. Results: Nup88 expression was higher in primary cancer tissues than in adjacent noncancerous tissues, and in the proximal and distant margins of normal mucosa. Overexpression of Nup88 mRNA was statistically associated with TNM stage (P = 0.044), lymphatic metastasis (P = 0.022), and cancer location (P = 0.036), while not related to gender, age of patients and histological type, infiltration depth, and differentiation of cancers. The expression of Nup88 mRNA in the HCT-116 (P53-/-) cell line was not significantly different from expression in the HCT-116 (P53+/+) cell line. And there was no correlation between Nup88 and p53 protein expression (r = 0.632, P = 0.368). Conclusions: Nup88 mRNA was overexpressed in colorectal cancers and the overexpression was associated with cancer development and aggressiveness. Nup88 might be regard as essential contributor to nodal metastagenicity of colorectal cancer.

45678 301 - 350 of 359
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