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  • 51.
    Jansson, Agneta K.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Emterling, Anna M.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    The BH3-only member Noxa may not be involved in the development of unselected colorectal cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Noxa is an BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Further, we searched for mutations in the Noxa gene using single stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumours and decreased in 9% and increased in 16% of the tumours compared to the normal mucosa, but these changes did not have any clinical or pathological significance. We did not find any mutations in the gene. Thus, our observations suggest that the variations in Noxa gene may not be of particular importance in the development of unselected colorectal cancer.

  • 52.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Bax expression decreases significantly from primary tumor to metastasis in colorectal cancer2002In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 20, no 3, p. 811-816Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Bax is a proapoptotic member of the bcl-2 family. Previous studies about Bax have shown that the expression increases from normal to tumor tissue, but the clinical significance is contradictory. Our aims were to analyze the expression of Bax from normal mucosa to primary tumor and to metastases in colorectal cancer patient. We further investigated whether low Bax expression in the primary tumor or changed expression from normal mucosa to primary tumor and to metastases had biologic and clinical significance.

    PATIENTS AND METHODS: The study included 135 patients with primary colorectal adenocarcinoma, of whom 31 had metastases in the lymph nodes and 75 had normal mucosa. Immunohistochemistry, DNA sequencing, and microsatellite analysis were used to detect Bax expression, mutations, and microsatellite instability.

    RESULTS: The protein was observed in 132 of 135 tumors, all normal epithelial cells and metastases. The frequencies of weak expression were greater from well/moderately to poorly differentiated and to mucinous carcinomas. Bax expression was stronger from normal to tumor tissue, but subsequently decreased in metastases. The matched cases with lower expression in the metastases than in the primary tumor showed a more infiltrative growth pattern and more distal metastases.

    CONCLUSION: The association of Bax expression with tumor differentiation/histologic types and a decreased expression in the metastases, suggests that Bax expression may be involved in tumor differentiation/histologic types and metastatic progression. We also propose the novel notion that changed Bax expression in the metastases compared with the primary tumors might provide information to determine the clinicopathologic characteristics of the tumor.

  • 53.
    Jansson, Agneta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Ki-67 expression in relation to clinicopathological variables and prognosis in colorectal adenocarcinomas1997In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 105, no 9, p. 730-734Article in journal (Refereed)
    Abstract [en]

    Ki-67 is a protein associated with cell proliferation which is expressed in all phases of the cell cycle except Go. In the present study, Ki-67 expression in 255 human colorectal adenocarcinomas was examined using immunohistochemistry with the monoclonal antibody MIB-1. One hundred and fifty-seven (62%) cases had more than 50% positive tumour cells and 98 (38%) cases less than 50%. The tumours showed a wide range of Ki-67 expression, from 13% to 90%, which indicated a variation in proliferative activity. There was no significant relationship between Ki-67 expression and sex, age, tumour location, Dukes' stage, growth pattern, differentiation, DNA content, S-phase fraction or survival (p > 0.05). In conclusion, the proliferative activity as measured by Ki-67 antibody was not related to clinicopathology and prognosis in colorectal cancer.

  • 54.
    Jung, Michaela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    A clinical study of metastasized rectal cancer treatment: assessing a multimodal approach2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, p. 839-Article in journal (Refereed)
    Abstract [en]

    Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11%) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery.

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  • 55.
    Kertat, Khadua
    et al.
    Department of Experimental and Clinical Medicine Linköping University.
    Rosdahl, Inger
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Synnerstad, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology .
    The Gln/Gln genotype of XPD codon 751 as a genetic marker for melanoma risk and Lys/Gln as an important predictor for melanoma progression: A case control study in the Swedish population2008In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 20, no 1, p. 179-183Article in journal (Refereed)
    Abstract [en]

    The Xeroderma pigmentosum complementation group D (XPD) is a critical protein in the nucleotide excision repair system for DNA damage. Genetic variations in XPD exert an important effect on the capacity of DNA repair. In this study, we examined Lys751Gln polymorphism at the XPD gene in 244 melanoma patients and 251 healthy individuals (as controls) from the south-eastern region of Sweden. The associations of polymorphism with melanoma risk, as well as with melanoma features and pigment phenotypes of the melanoma patients were analysed. DNA was extracted from the mononuclear cells of venous blood of the melanoma patients and controls. XPD codon 751 was genotyped by the PCR restriction fragment length polymorphism technique. Results showed that there was no difference in the distribution of the XPD codon 751 genotypes between the melanoma patients and healthy controls. However, the Gln/Gln genotype was found to be associated with melanoma risk in the male population. Furthermore, the frequency of the Gln/Gln genotype was significantly higher in the early stages of melanomas, whereas Lys/ Gln was more frequent in the later stages and in the patients with melanoma located on intermittently UV-exposed areas. No correlations between the polymorphisms and phenotypes of the patients were found. In conclusion, Gln/Gln was a useful genetic marker for melanoma risk in the males, while Lys/Gln was an important predictor for melanoma progression.

  • 56.
    Knutsen Holmqvist, Annica
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Inflammatory infiltration, fibrosis, necrosis and mucinous content in relation to clinicopathological and molecular factors in rectal cancers with or without preoperative radiotherapy.2006In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 16, no 2, p. 321-327Article in journal (Refereed)
    Abstract [en]

    The association between inflammatory infiltration, fibrosis, necrosis and mucinous content in rectal cancers, and their relationship to preoperative radiotherapy (RT) clinicopathological and biological factors (p53, apoptosis and Cox-2) is not fully characterised. We analysed these histopathological parameters and their relationships in rectal cancer patients who participated in a clinical trial of preoperative RT. One hundred and forty-eight preoperative biopsies and 153 surgically resected tumours were examined. Of the surgical specimens, 81 had surgery alone and 72 received RT before surgery. A higher grade of inflammatory infiltration was related to favourable survival in the whole group of patients (p=0.004, for multivariate analysis p=0.01) as well as in the subgroups of patients with (p=0.04) or without RT (p=0.01). After RT, tumours showed a decreased infiltration (p=0.0003) and increased necrosis (p=0.006), strong necrosis was related to favourable survival (p=0.046). Necrosis (p=0.054) and fibrosis (p=0.06) tended to be increased in p53-negative tumours after RT. Inflammatory infiltration was a strong prognostic factor in rectal cancer patients, regardless of RT. RT tended to induce necrosis and fibrosis in p53-negative tumours.

  • 57.
    Knutsen Holmqvist, Annica
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy2004In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 60, no 1, p. 149-155Article in journal (Refereed)
    Abstract [en]

    Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT. Methods and Materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery. Results: Survivin positivity was related to worse survival, independent of Dukes' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71). Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. (C) 2004 Elsevier Inc.

  • 58.
    Kopsida, Maria
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Liu, Na
    Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China.
    Kotti, Angeliki
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Wang, Jing
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Jensen, Lasse D
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Jothimani, Ganesan
    Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India.
    Hildesjö, Camilla
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Zhong, Wen
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Pathak, Surajit
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India .
    Sun, Xiao-Feng
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    RhoB expression associated with chemotherapy response and prognosis in colorectal cancer2024In: Cancer Cell International, E-ISSN 1475-2867, Vol. 24, no 1, article id 75Article in journal (Refereed)
    Abstract [en]

    Purpose: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients.

    Materials and methods: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data.

    Results: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration.

    Conclusion: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

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  • 59.
    Kotti, Angeliki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist (Knutsen), Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    SPARCL1 Expression Increases With Preoperative Radiation Therapy and Predicts Better Survival in Rectal Cancer Patients2014In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 88, no 5, p. 1196-1202Article in journal (Refereed)
    Abstract [en]

    Purpose

    The secreted protein acidic and rich in cysteine-like 1 (SPARCL1) is expressed in various normal tissues and many types of cancers. The function of SPARCL1 and its relationship to a patient's prognosis have been studied, whereas its relationship to radiation therapy (RT) is not known. Our aim was to investigate the expression of SPARCL1 in rectal cancer patients who participated in a clinical trial of preoperative RT.

    Methods and Materials

    The study included 136 rectal cancer patients who were randomized to undergo preoperative RT and surgery (n=63) or surgery alone (n=73). The expression levels of SPARCL1 in normal mucosa (n=29), primary tumor (n=136), and lymph node metastasis (n=35) were determined by immunohistochemistry.

    Results

    Tumors with RT had stronger SPARCL1 expression than tumors without RT (P=.003). In the RT group, strong SPARCL1 expression was related to better survival than weak expression in patients with stage III tumors, independent of sex, age, differentiation, and margin status (P=.022; RR = 18.128; 95% confidence interval, 1.512-217.413). No such relationship was found in the non-RT group (P=.224). Further analysis of interactions among SPARCL1 expression, RT, and survival showed statistical significance (P=.024). In patients with metastases who received RT, strong SPARCL1 expression was related to better survival compared to weak expression (P=.041) but not in the non-RT group (P=.569).

    Conclusions

    SPARCL1 expression increases with RT and is related to better prognosis in rectal cancer patients with RT but not in patients without RT. This result may help us to select the patients best suited for preoperative RT.

  • 60.
    Lewander, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Dept Surg Ostergotland, Norrkoping, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Polymorphism in the promoter region of the NFKBIA gene is rare in Swedish and Chinese colorectal cancer patients and controls2010In: MOLECULAR MEDICINE REPORTS, ISSN 1791-2997, Vol. 3, no 1, p. 69-74Article in journal (Refereed)
    Abstract [en]

    To investigate whether a -708ins/del8 polymorphism in the promoter region of the NFKBIA gene is related to colorectal cancer risk and clinicopathological variables, we, genotyped 92 Swedish and 93 Chinese patients as well as 174 Swedish and 159 Chinese healthy controls by polymerase chain reaction-single stranded conformation polymorphism and DNA sequencing. The -708/del8 polymorphism was found in two Swedish patients and eight Swedish controls, but was absent in the Chinese population. However, among the Chinese population we found other mutations in three patients and in one control. In conclusion, the -708ins/del8 polymorphism is too rare to have a major impact on colorectal cancer incidence in the two populations.

  • 61.
    Lewander, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Adell, G.
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of NF-κB p65 phosphorylated at Serine-536 in rectal cancer with or without preoperative radiotherapy2011In: RADIOLOGY AND ONCOLOGY, ISSN 1318-2099, Vol. 45, no 4, p. 279-284Article in journal (Refereed)
    Abstract [en]

    In the present study, we investigated NF-κB p65 phosphorylated at Serine-536 (phospho-Ser536-p65) in rectal cancer and its relationship to radiotherapy (RT) and clinicopathological and biological factors. Expression of phospho-Ser536-p65 was examined by using immunohistochemistry in 141 primary rectal cancers, 149 normal mucosa specimens and 48 metastases in the lymph nodes, from rectal cancer patients randomized to received RT or not. The expression of phospho-Ser536-p65 in the cytoplasm increased from normal mucosa to primary tumor (p<0.0001, for both RT and non-RT groups). The expression did not further increased from primary tumor to metastases in the either group (p>0.05). We found that the expression of phospho-Ser536-p65 was positively related to or tended to be positively related to expression of TEM1 (p=0.02), FXYD-3 (p=0.0006), PRL (p=0.02), p73 (p=0.048) and MAC30 (p=0.051) in the RT group but there were no such relationships in the non-RT group (p>0.05). The expression of the phospho-Ser536-p65 was not related to clinicopathological factors including survival (p>0.05). The increased expression of phospho-Ser536-p65 may be involved in rectal cancer development. After RT, the expression of NF-κB seems to be positively related to the biological factors which associated with more malignant features of tumors. However, we did not find that the phospho-Ser536-p65 was directly related to clinical response of RT.

  • 62.
    Lewander, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    NF-κB p65 phosphorylated at Serine-536 is an independent prognostic factor in Swedish colorectal cancer patientsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: NF-κB transcription factor protein family has diverse cellular and biological functions, and post-translational modification is important to regulate these functions. An important site of phosphorylation of p65 subunit is at Serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization and protein stability. In this study, we investigated a phospho-Ser536-p65 in colorectal cancers and its relationship to clinicopathological factors of the patients.

    Materials and Methods: Expression of phospho-Ser536-p65 was examined by using immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens and 18 metastases in the lymph nodes.

    Results: The expression of phospho-Ser536-p65 increased from normal mucosa to primary tumour (p<0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumours correlated with worse survival of the patients independent of gender, age, tumor location, stage and differentiation (p=0.04, hazard ratio 1.89, 95% CI 1.03-3.47).

    Conclusion: The NF-κB p65 subunit phosphorylated at Serine-536 is anindependent prognostic factor in colorectal cancer patients.

  • 63.
    Lewander, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery VHN.
    Zhang, Hong
    University of Skövde.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    NF-kappa B p65 phosphorylated at serine-536 is an independent prognostic factor in Swedish colorectal cancer patients2012In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 27, no 4, p. 447-452Article in journal (Refereed)
    Abstract [en]

    The NF-kappa B transcription factor protein family has diverse cellular and biological functions, and posttranslational modification is important to regulate these functions. An important site of phosphorylation of NF-kappa B p65 subunit is at serine-536 (phospho-Ser536-p65), and this phosphorylation is involved in regulation of transcriptional activity, nuclear localization, and protein stability. less thanbrgreater than less thanbrgreater thanIn this study, we investigated expression of phospho-Ser536-p65 in colorectal cancers and its relationships with clinicopathological factors. The expression of phospho-Ser536-p65 was examined by immunohistochemistry in 203 primary colorectal cancers, 156 normal mucosa specimens, and 18 metastases in the lymph nodes. less thanbrgreater than less thanbrgreater thanThe expression of phospho-Ser536-p65 increased from normal mucosa to primary tumor (p andlt; 0.0001). Further, the increased expression of phospho-Ser536-p65 in the cytoplasm of the primary tumors correlated with worse survival of the patients independently of gender, age, tumor location, stage, and differentiation (p = 0.04; hazard ratio, 1.89; 95% CI 1.03-3.47). less thanbrgreater than less thanbrgreater thanThe NF-kappa B p65 subunit phosphorylated at serine-536 is an independent prognostic factor in colorectal cancer patients.

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  • 64.
    Lewander, Andreas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Kumar Reddy Butchi, Anil
    Gao, Jingfang
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    He, Lu-Jun
    Lindblom, Annika
    Arbman, Gunnar
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Zhang, Zhi-Yong
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Polymorphism in the promoter region of the NFKB1 gene increases the risk of sporadic colorectal cancer in Swedish but not in Chinese populations2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 11, p. 1332-1338Article in journal (Refereed)
    Abstract [en]

    Objective. An insertion/deletion polymorphism (-94ins/delATTG) in the promoter region of the NFKB1 gene correlates to an increased risk of ulcerative colitis, a known risk factor for colorectal cancer, but this polymorphism has not been studied in colorectal cancer patients. The purpose of this study was to investigate whether this polymorphism is related to colorectal cancer risk and clinicopathological variables. Material and methods. Case samples were taken from four groups of Swedish patients: 193 unselected patients, 90 patients with ≥3 affected 1st-degree relatives, 85 patients with 2 affected 1st-degree relatives, and 109 sporadic cancer patients, and one group of 193 unselected Chinese patients. Controls included 439 Swedish and 458 Chinese healthy individuals. Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Results. The deletion increased the risk of colorectal cancer among Swedish unselected patients (OR=3.81, 95% CI: 2.17-6.69, p<0.0001 for heterozygote deletion, and OR=4.65, 95% CI: 2.43-8.89, p<0.0001 for homozygote deletion) and sporadic cancer patients (OR=7.73, 95% CI: 3.06-19.57, p<0.0001 for heterozygote deletion, and OR=6.58, 95% CI: 2.35-18.43, p<0.0001 for homozygote deletion) compared to homozygote insertion (wild-type), but not among the other Swedish or Chinese patients (p>0.05). Similar evidence was seen in age-adjusted analyses (p<0.0001). The polymorphism did not correlate to clinicopathological variables (p>0.05). Conclusions. Deletion of the polymorphism was associated with increased susceptibility to sporadic colorectal cancers in the Swedish population, but not in the Swedish patients with a family history of colorectal cancer or in Chinese patients. © 2007 Taylor & Francis.

  • 65.
    Li, Yifei
    et al.
    Hebei Medical University, Peoples R China.
    Zhang, Xia
    Hebei Medical University, Peoples R China.
    Ge, Jing
    Hebei Medical University, Peoples R China.
    Liu, Xiaoli
    Hebei Medical University, Peoples R China.
    Xu, Shuwen
    Hebei Medical University, Peoples R China.
    Zhu, Zhenlong
    Hebei Medical University, Peoples R China.
    Fang, Guiying
    Hebei Medical University, Peoples R China.
    Liu, Jing
    Hebei Medical University, Peoples R China.
    Zhang, Hongzhen
    Hebei Medical University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study2016In: Pathology, Research and Practice, ISSN 0344-0338, E-ISSN 1618-0631, Vol. 212, no 4, p. 274-278Article in journal (Refereed)
    Abstract [en]

    Background: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. Aims: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. Methods: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. Results: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P &lt; 0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P = 0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P = 0.033). Conclusions: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer. (C) 2016 Elsevier GmbH. All rights reserved.

  • 66.
    Li, Yifei
    et al.
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Zhang, Xia
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Xu, Shuwen
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Ge, Jing
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Liu, Jing
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Li, Lin
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Fang, Guiying
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Meng, Yali
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Zhang, Hongzhen
    First Hospital of Hebei Medical University, Shijiazhuang, China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Expression and clinical significance of FXYD3 in endometrial cancer2014In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 2, p. 517-522Article in journal (Refereed)
    Abstract [en]

    FXYD3 expression is upregulated in numerous cancer cell types. The present study compared the FXDY3 expression in normal endometrium, premalignant lesion and endometrial cancer tissue samples, and investigated the correlation between FXDY3 expression and clinicopathological features. FXYD3 expression was analyzed by streptavidin-peroxidase immunohistochemistry in 21 normal endometrial tissue samples, 18 atypical endometrial hyperplasia samples and 50 tissues obtained from patients diagnosed with endometrial cancer. The percentage of FXYD3-positive cell expression in the normal endometrium, atypical hyperplasia and endometrial cancer tissues samples was 0, 22, and 26%, respectively. The differences between the atypical hyperplasia and endometrial cancer groups were statistically significant when compared with the normal group (P=0.007 and P=0.037, respectively). There was no significant difference between the atypical hyperplasia and endometrial cancer groups. The percentage of FXYD3-positive cells correlated with the fertility frequency (Pless than0.05). In conclusion, FXYD3 is a potential biomarker for endometrial cancer, and its upregulation may be an early event in endometrial carcinoma progression. In addition, FXYD3 expression in endometrial carcinoma correlates with fertility frequency.

  • 67.
    Liu, Guang-Hui
    et al.
    Sichuan University, China.
    Zhou, Zong-Guang
    Sichuan University, China.
    Chen, Rong
    Sichuan University, China.
    Wang, Mon-Jin
    Sichuan University, China.
    Zhou, Bin
    Sichuan University, China.
    Li, Yuan
    Sichuan University, China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer2013In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 34, no 4, p. 2175-2181Article in journal (Refereed)
    Abstract [en]

    Previous studies from our laboratory identified a number of miRNAs that were aberrantly expressed in colorectal cancer (CRC) tissue. However, their diagnostic and prognostic value in serum has not been fully evaluated. In the present study, we measured the levels of five miRNAs (miR-21, miR-31, miR-92a, miR-18a, and miR-106a) in serum samples from 200 CRC patients, 50 advanced adenoma patients, and 80 healthy controls by real-time quantitative polymerase chain reaction (RT-PCR). In our study, the levels of miR-21 and miR-92a in patients with CRC and advanced adenoma were significantly higher than those in healthy controls (all P  < 0.05). MiR-21 yielded an area under the receiver-operating characteristics (ROC) curve (AUC) of 0.802 and miR-92a yielded an AUC of 0.786 in discriminating CRCs from the controls. Additionally, miR-21 and miR-92a yielded an AUC of 0.709 and 0.701, respectively, in discriminating advanced adenomas from the controls. Combined ROC analyses using both miRNAs, revealed an elevated AUC of 0.847 in discriminating CRCs, and an AUC of 0.722 in discriminating advanced adenomas from the controls. In the multivariate Cox proportional hazards analysis, high miR-92a expression in CRC was independently associated with poor survival (P = 0.03; hazard ratio 4.36; 95 % confidence interval = 1.64–11.57). No significant difference was observed in the levels of miR-18a, miR-31, and miR-106a among CRC, advanced adenoma, and control samples. In summary, our data indicate that miR-21 and miR-92a serum levels have potential value for early detection of CRC. Furthermore, miR-92a has prognostic value in CRC patients.

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  • 68.
    Liu, H.-Y.
    et al.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China, Shanxi Cancer Hospital, Taiyuan, China.
    Zhou, B.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Wang, L.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Li, Y.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Zhou, Z.-G.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China, National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China, Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Xu, B.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Zeng, Y.-J.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Song, J.-M.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Luo, H.-Z.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Yang, L.
    Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
    Association of E1AF mRNA expression with tumor progression and matrilysin in human rectal cancer2007In: Oncology, ISSN 0030-2414, E-ISSN 1423-0232, Vol. 73, no 5-6, p. 384-388Article in journal (Refereed)
    Abstract [en]

    Objective: To examine E1AF mRNA expression and to determine whether it is correlated with tumor progression and matrilysin in human rectal cancer. Methods: Real-time RT-PCR was used to determine E1AF and matrilysin expression in 100 matched rectal cancers and normal tissues. Results: Among the 100 rectal cancers, 69 cases of E1AF mRNA overexpression were observed. E1AF mRNA overexpression correlated well with matrilysin. In carcinomas, E1AF mRNA overexpression correlated significantly with depth of invasion, lymph node metastasis, venous involvement and advanced pTNM stage. Conclusions: E1AF was correlated significantly with tumor progression of human rectal cancer and may be an important factor in rectal cancer progression. Copyright © 2008 S. Karger AG.

  • 69.
    Liu, Na
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China.
    Cox, Thomas R.
    Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
    Cui, Weiyingqi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Ping, Jie
    Shanghai Center for Bioinformation Technology, Shanghai, China.
    Jarlsfelt, Ingvar
    Department of Pathology, Ryhov Hospital, Jönköping, Sweden.
    Erler, Janine T.
    Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients.2017In: Oncotarget, E-ISSN 1949-2553, Vol. 8, no 36, p. 60015-60024Article in journal (Refereed)
    Abstract [en]

    Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.

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  • 70.
    Liu, Yong
    et al.
    Sichuan University, Peoples R China.
    Zhou, Dan
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Chen, Ke-Ling
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Lv, Zhao-Yin
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury2016In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 310, no 5, p. G303-G309Article in journal (Refereed)
    Abstract [en]

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.

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  • 71.
    Lof-Ohlin, Zarah M
    et al.
    Orebro University Hospital.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Nilsson, Torbjorn K
    Orebro University Hospital.
    DNA methylation of the p14(ARF), RASSFIA and APCIA genes define a poor prognosis subset of colorectal cancer patients independently of tumor stage and tumor differentiation in INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, vol 26, issue , pp S5-S52010In: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Spandidos Publications , 2010, Vol. 26, p. S5-S5Conference paper (Refereed)
    Abstract [en]

    n/a

  • 72.
    Loftas, Per
    et al.
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Önnesjö, Sofia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology .
    Widegren, Emma
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology .
    Adell, Gunnar
    Karolinska University Hospital.
    Kayed, Hany
    University of Heidelberg.
    Kleeff, Joerg
    Tech University of Munich.
    Zentgraf, Hanswalter
    University of Heidelberg.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    EXPRESSION OF FXYD-3 IS AN INDEPENDENT PROGNOSTIC FACTOR IN RECTAL CANCER PATIENTS WITH PREOPERATIVE RADIOTHERAPY2009In: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, ISSN 0360-3016, Vol. 75, no 1, p. 137-142Article in journal (Refereed)
    Abstract [en]

    Purpose: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. Methods and Materials: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immumohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). Results: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0.02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to he increased compared with normal mucosa regardless of RT. Conclusion: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.

  • 73.
    Loof, Jasmine
    et al.
    University of Skovde, Sweden .
    Pfeifer, Daniella
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Ding, Zhen-Yu
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Zhang, Hong
    University of Skovde, Sweden .
    Effects of Delta Np73 beta on cisplatin treatment in colon cancer cells2012In: Molecular Carcinogenesis, ISSN 0899-1987, E-ISSN 1098-2744, Vol. 51, no 8, p. 628-635Article in journal (Refereed)
    Abstract [en]

    p73 can activate transcription of p53-responsive genes, thereby inhibiting cell growth. An alternative promoter in the TP73 gene gives rise to an N-terminally truncated isoform of p73, Delta Np73, which lacks the transactivation domain of the full length TAp73 protein. TAp73 is considered pro-apoptotic, and Delta Np73 anti-apoptotic. In this study, we overexpressed ?Np73 beta in p53 wild type and p53 mutant colon cancer cell lines and further exposed the cells to cancer therapeutic drug cisplatin. The results showed that cisplatin decreased the protein expression levels of Delta Np73 beta in a dose-dependent manner, and both TAp73 and p53 were upregulated after cisplatin treatment. Further, clonogenic potential and cell viability were decreased, and apoptotic cells increased, in p53 mutant and in p53 wild type cells. Cellular viability was significantly higher in Delta Np73 beta-cells than mock-transfected cells. However, Delta Np73 beta overexpression did not affect the cellular susceptibility to cisplatin. In conclusion, the overexpression of Delta Np73 beta increases viability in p53 wild type and p53 mutant colon cancer cells, and cisplatin induces the degradation of Delta Np73 beta in a dose-dependent manner.

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  • 74.
    Loof, Jasmine
    et al.
    University of Skovde.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Bratthall, Charlotte
    Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Doré, Siv
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Starkhammar, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Zhang, Hong
    University of Skovde.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Impact of PINCH expression on survival in colorectal cancer patients2011In: BMC CANCER, ISSN 1471-2407, Vol. 11, no 103Article in journal (Refereed)
    Abstract [en]

    Background: The adaptor protein PINCH is overexpressed in the stroma of several types of cancer, and is an independent prognostic marker in colorectal cancer. In this study we further investigate the relationship of PINCH and survival regarding the response to chemotherapy in colorectal cancer. Results: Paraffin-embedded tissue sections from 251 primary adenocarcinomas, 149 samples of adjacent normal mucosa, 57 samples of distant normal mucosa and 75 lymph node metastases were used for immunohistochemical staining. Stromal staining for PINCH increased from normal mucosa to primary tumour to metastasis. Strong staining in adjacent normal mucosa was related to worse survival independently of sex, age, tumour location, differentiation and stage (p = 0.044, HR, 1.60, 95% Cl, 1.01-2.52). PINCH staining at the invasive margin tended to be related to survival (p = 0.051). In poorly differentiated tumours PINCH staining at the invasive margin was related to survival independently of sex, age and stage (p = 0.013, HR, 1.90, 95% Cl, 1.14-3.16), while in better differentiated tumours it was not. In patients with weak staining, adjuvant chemotherapy was related to survival (p = 0.010, 0.013 and 0.013 in entire tumour area, invasive margin and inner tumour area, respectively), but not in patients with strong staining. However, in the multivariate analysis no such relationship was seen. Conclusions: PINCH staining in normal adjacent mucosa was related to survival. Further, PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status.

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  • 75.
    Lööf, Jasmine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Pfeifer, Daniella
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Adell, Gunnar
    Karolinska University Hospital.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy2009In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 92, no 2, p. 215-220Article in journal (Refereed)
    Abstract [en]

    Background and Purpose: An exon 2 G4C14→A4T14 polymorphism in the p73 gene was shown to be related to survival in several types of cancers, including colorectal cancer. The purpose was to investigate if this polymorphism was related to survival in rectal cancer patients with or without preoperative radiotherapy.

    Material and Methods: DNA extracted from tissue of 138 rectal cancer patients that received preoperative radiotherapy or had surgery alone was typed for the polymorphism by PCR using confronting two-pair primers.

    Results: Among patients, 69% had GC/GC genotype, 27% GC/AT and 4% AT/AT. In the radiotherapy group, patients carrying the AT (GC/AT+AT/AT) allele had stronger expression of p53 (p=0.001) and survivin protein (p=0.03) than those carrying the GC/GC genotype. Further, among patients receiving preoperative radiotherapy the GC/GC genotype tended to be related to better survival (p=0.20). Patients with GC/GC genotype, along with negative p53 and weak survivin expression showed better survival than the other patients (p=0.03), even after adjusting for TNM stage and tumor differentiation (p=0.01, RR, 7.63, 95% CI, 1.50-38.74). In the non-radiotherapy group, the polymorphism was not related to survival (p=0.74).

    Conclusions: Results suggest that the p73 G4C14→A4T14 polymorphism could be one factor influencing outcome of preoperative radiotherapy in rectal cancer patients.

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  • 76.
    Maguire, P.
    et al.
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Margolin, S.
    Department of Oncology, Karolinska University Hospital, Södersjukhuset, Stockholm, Sweden.
    Skoglund, J.
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Gustafsson, J.-A.
    Gustafsson, J.-Å., Department of Medical Nutrition, Karolinska Institute, Novum, Huddinge, Sweden.
    Borresen-Dale, A.-L.
    Børresen-Dale, A.-L., Department of Genetics, Norwegian Radium Hospital, University of Oslo, Montebello, Oslo, Norway.
    Lindblom, A.
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden, Department of Molecular Medicine, CMM L8:02, Karolinska Institute, S-171 76 Stockholm, Sweden.
    Estrogen receptor beta (ESR2) polymorphisms in familial and sporadic breast cancer2005In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 94, no 2, p. 145-152Article in journal (Refereed)
    Abstract [en]

    Estrogen is involved in both normal mammary development and in breast carcinogenesis. A family history of disease and exposure to estrogen are major risk factors for developing breast cancer. Estrogen exerts its biological effects through binding to the estrogen receptors, estrogen receptor alpha (ESR1) and the more recently discovered estrogen receptor beta (ESR2). Genetic variation in genes involved in estrogen biosynthesis, metabolism and signal transduction have been suggested to play a role in breast cancer risk. We therefore tested the hypothesis that common genetic variants of the ESR2 gene may be associated with increased risk for breast cancer and this risk may vary between breast cancer groups. We investigated three common ESR2 polymorphisms, rs1256049 (G1082A), rs4986938 (G1730A) and rs928554 (Cx+56 A?G) for association to breast cancer risk. A total of 723 breast cancer cases and 480 controls were included in the study. Of the breast cancer cases, 323 were sporadic and 400 were familial, the familial cases were further divided into familial high-risk and familial low-risk breast cancer cases. We found no overall statistically significant association for any of the single polymorphisms studied. Haplotype analysis suggested one haplotype associated with increased risk in sporadic breast cancer patients (OR = 3.0, p = 0.03). Further analysis is needed to elucidate the role of estrogen receptor beta in breast cancer susceptibility. © Springer 2005.

  • 77.
    Meng, N.
    et al.
    Department of Surgery The Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
    Li, Y.
    Department of Surgery The Forth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
    Zhang, H.
    Division of Biomedicine School of Life Science, University of Skövde, Skövde,.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    RECK, a novel matrix metalloproteinase regulator2008In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 23, no 7-9, p. 1003-1010Article in journal (Refereed)
    Abstract [en]

    Extracellular matrix (ECM) macromolecules are important for creating the cellular environments required during development and morphogenesis of tissues. Matrix metalloproteinases (MMPs) are a family of Zn-dependent endopeptidases that collectively are capable of cleaving virtually all ECM substrates, and play an important role in some physiological and pathological processes. MMP activity can be inhibited by some natural and artificial inhibitors. A newly found membrane-anchored regulator of MMPs, the reversion-inducing-cysteine-rich protein with kazal motifs (RECK), is downregulated when the cells undergo a process of malignant transformation, and is currently the subject of considerable research activity because of its specific structure and function. In this review, we have chosen to concentrate our efforts on the structure, function, regulation, and future prospect of RECK in order to provide a new target for prevention and treatment of tumours.

  • 78.
    Meng, Wen-Jian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Pathak, Surajit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ding, Zhen-Yu
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer2015In: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 16, no 12, p. 1738-1745Article in journal (Refereed)
    Abstract [en]

    Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasnt been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.

  • 79. Meng, Wen-Jian
    et al.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Tian, Chao
    Wang, Ling
    Yu, Yong-Yang
    Zhou, Bing
    Gu, Jun
    Xia, Qing-Jie
    Li, Yuan
    Wang, Rong
    Zheng, Xue-Lian
    Zhou, Zong-Guang
    Microsatellite instability did not predict individual survival in sporadic stage II and III rectal cancer patients2007In: Oncology, ISSN 0890-9091, Vol. 72, no 1-2, p. 82-88Article in journal (Refereed)
    Abstract [en]

    Objectives: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients. Methods: DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used. Results: Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively). Conclusions: Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients. Copyright © 2007 S. Karger AG.

  • 80. Meng, Wen-Jian
    et al.
    Wang, Ling
    Tian, Chao
    Yu, Yong-Yang
    Zhou, Beng
    Gu, Yun
    Xia, Qing-Jie
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Li, Yuan
    Wang, Rong
    Zheng, Xue-Lian
    Zhou, Zong-Guang
    Novel mutations and sequence variants in exons 3-9 of human T Cell Factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability2007In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 13, no 27, p. 3747-3751Article in journal (Refereed)
    Abstract [en]

    Aim: To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI). Methods: Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used. Results: Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls. Conclusion: Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H. © 2007 WJG. All rights reserved.

  • 81.
    Meng, Wen-Jian
    et al.
    Sichuan University.
    Yan, Hui
    Sichuan University.
    Zhou, Bin
    Sichuan University.
    Zhang, Wei
    Sichuan University.
    Kong, Xiang-Heng
    Sichuan University.
    Wang, Rong
    Sichuan University.
    Zhan, Lan
    Sichuan University.
    Li, Yuan
    Sichuan University.
    Zhou, Zong-Guang
    Sichuan University.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Correlation of SATB1 overexpression with the progression of human rectal cancer2012In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 27, no 2, p. 143-150Article in journal (Refereed)
    Abstract [en]

    To date, the association between special AT-rich sequence-binding protein 1 (SATB1) and colorectal cancer (CRC) has not been reported. This study was aimed at investigating the expression and potential role of SATB1 in human rectal cancers. less thanbrgreater than less thanbrgreater thanNinety-three paired samples of rectal cancer and distant normal rectal tissue were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and the correlations between SATB1 expression and clinicopathological parameters were evaluated. The expression profiles of SATB1 were also investigated in a panel of five human colon carcinoma cell lines. less thanbrgreater than less thanbrgreater thanThe general level of SATB1 mRNA in rectal cancer tissues was statistically significantly higher than that in normal mucosa (P = 0.043). The rate of positive SATB1 protein expression in rectal cancers (44.1%) was significantly higher than that in normal tissues (25.8%) by IHC analysis (P = 0.009). Overexpression of SATB1 mRNA was more predominant in patients with earlier onset of rectal cancer (P = 0.033). SATB1 expression correlated with invasive depth and tumor node metastasis (TNM) stage at both protein and mRNA levels (P andlt; 0.05). Furthermore, SATB1 expression in the poorly metastatic KM12C cells was significantly lower than the highly metastatic KM12SM and KM12L4A cells and higher than the HCT116 and SW480 cells (P = 0.001). These results were further confirmed by Western blotting. less thanbrgreater than less thanbrgreater thanOur results indicate that SATB1 may play an important role in the progression of human rectal cancer, which represents a possible new mechanism underlying CRC.

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  • 82.
    Meng, Wen-Jian
    et al.
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Ma, Qin
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Wang, Zi-Qiang
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer2015In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 32Article in journal (Refereed)
    Abstract [en]

    The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.

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  • 83.
    Miger, Jasmine
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Low-dose capecitabine (Xeloda) for treatment for gastrointestinal cancer2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, p. 870-Article in journal (Refereed)
    Abstract [en]

    The prodrug capecitabine (Xeloda) has been an important drug for treatment for gastrointestinal cancer (GI-cancer). This study explores the efficacy of continuous metronomic Xeloda, as well as tolerability and best response during treatment. Patients (n=35) with stage IV GI-cancer were included in the study and were divided into two groups; upper (n=13) and lower (n=22) GI-cancer. All patients were given continuous metronomic Xeloda (500 mg×2). Best response was measured by radiological and clinical examination including laboratory results. Standard RECIST criteria were used. Median age was 66 (range 29-86). Those patients who received first and second line had the longest duration of treatment. For patients with metastatic gastrointestinal cancer, metronomic capecitabine (Xeloda) may be beneficial both as far as tumor control and quality of life is concerned. In this pilot study, palliation for more than 2 years is observed for 6 of the 35 patients.

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  • 84.
    Moparhti, Satish Babu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Kayed, Hany
    General Surgery, University of Heidelberg, Heidelberg, Germany.
    Kleeff, Jörg
    General Surgery, University of Heidelberg, Heidelberg, Germany.
    Zentgraf, Hanswalter
    Applied Tumor Virology, University of Heidelberg, Heidelberg, Germany.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers2007In: International Journal of Oncology, ISSN 1019-6439, E-ISSN 1791-2423, Vol. 30, no 1, p. 91-95Article in journal (Refereed)
    Abstract [en]

    MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.

  • 85.
    Moparthi, Satish Babu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Bergman, Viveka
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Adell, Gunnar
    Karolinska University Hospital.
    Thorstensson, Sten
    Kalmar Hospital.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    pRb2/p130 protein in relation to clinicopathological and biological variables in rectal cancers with a clinical trial of preoperative radiotherapy2009In: INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, ISSN 0179-1958, Vol. 24, no 11, p. 1303-1310Article in journal (Refereed)
    Abstract [en]

    pRb2/p130 plays a key role in cell proliferation and is a considerable progress about expression patterns of pRb2/p130 in number of malignancies. However, pRb2/p130 expression and its significance in rectal cancer remain unknown. The purpose of the present study was to investigate pRb2/p130 protein patterns and their correlations with clinicopathological and biological factors in rectal cancer patients with or without preoperative radiotherapy (RT). pRb2/p130 protein was examined by immunohistochemistry in 130 primary tumors, along with the corresponding 61 distant normal mucosa specimens, 85 adjacent normal mucosa specimens, 34 lymph node metastases, and 93 primary tumor biopsies from rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. The pRb2/p130 protein was mainly localized in the cytoplasm of tumor cells. In nonradiated cases, the lack of pRb2/p130 was related to advanced tumor-node-metastases stage, poorer differentiation, weak fibrosis, less inflammatory infiltration, higher Ki-67, and positive Cox-2 expression (p andlt; 0.05). In radiated cases, the lack of pRb2/p130 was related to nonstaining of Cox-2 and survivin (p andlt; 0.05). pRb2/p130 protein in primary tumors tended to be increased after RT (27% vs 16%, p = 0.07). pRb2/p130 was mainly localized in the cytoplasm rather than in the nucleus in rectal cancer. After RT, pRb2/p130 protein seems to be increased in primary tumors, and further the relationship of the pRb2/p130 with the clinicopathological and biological variables changed compared to the nonradiated cases. However, we did not find that the pRb2/p130 was directly related to RT, tumor recurrence, and patients survival.

  • 86. Murthy, RV
    et al.
    Arbman, G
    Gao, Jingfang
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Roodman, D
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer2005In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 11, no 6, p. 2293-2299Article in journal (Refereed)
    Abstract [en]

    Purpose: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopatbologic and biological variables in colorectal cancers. Experimental Design: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. Results: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/ mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. Conclusions: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients. ©2005 American Association for Cancer Research.

  • 87.
    Nilsson, Torbjorn K.
    et al.
    Örebro University Hospital, Sweden University of Örebro, Sweden .
    Lof-Ohlin, Zarah M.
    Örebro University Hospital, Sweden .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    DNA methylation of the p14(ARF), RASSF1A and APC1A genes as an independent prognostic factor in colorectal cancer patients2013In: International Journal of Oncology, ISSN 1019-6439, E-ISSN 1791-2423, Vol. 42, no 1, p. 127-133Article in journal (Refereed)
    Abstract [en]

    We quantitated the methylated fraction of CpG sites in the promoter regions of O-6-MGMT, p14(ARF), p16(INK4a), RASSF1A and APC1A in tumor tissue from patients with colorectal cancer (CRC) in order to determine if promoter hypermethylation of any of these genes predicts survival. DNA was isolated from 111 primary CRC and 46 matched normal colorectal mucosa samples from the same patients, obtained at primary surgery and DNA methylation was examined by Pyrosequencing (R). Follow-up time was up to 20 years. Patients showed partial promoter methylation in the following frequencies: O-6-MGMT, 34%; p14(ARF), 29%; p16(INK4a), 28%; RASSF1A, 14%; and APC1A, 27%. Normal mucosa was always unmethylated. CRC patients with methylated p14(ARF). gene promoter had significantly worse prognosis (p=0.036), whereas those with methylated O-6-MGMT had significantly better prognosis through the first 60 months post-treatment (RR 0.36; p=0.023). Methylation of one or more of the genes from the set p14(ARF), RASSF1A and APC1A, was significantly (p=0.021) associated with worse prognosis even adjusting for tumor stage and differentiation (RR 2.2, p=0.037). Thus, DNA methylation of the p14(ARF), RASSF1A and APC1A genes, diagnosed by Pyrosequencing, defines a poor prognosis subset of CRC patients independently of both tumor stage and differentiation. O-6-MGMT methylation may play a protective role.

  • 88. Pachkoria, Ketevan
    et al.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Jarlsfelt, Ingvar
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy2005In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 63, no 3, p. 739-744Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p ≤ 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors. © 2005 Elsevier Inc.

  • 89.
    Pathak, Surajit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Meng, Wen-Jian
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China.
    Kumar Nandy, Suman
    University of Kalyani, India.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Bisgin, Atil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Helmfors, Linda
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Waldmann, Patrik
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner2015In: Oncotarget, E-ISSN 1949-2553, Vol. 6, no 42, p. 44758-44780Article in journal (Refereed)
    Abstract [en]

    Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan (R) miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-alpha, IL-1 beta, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1 alpha were increased, and IFN-gamma expression was decreased after radiation, whereas, IL-6, IFN-gamma, TNF-alpha, IL-1 beta, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1 alpha were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.

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  • 90.
    Pathak, Surajit
    et al.
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    S, Sushmitha
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Banerjee, Antara
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Marotta, Francesco
    ReGenera Research Group for Aging-Intervention, Milano, Italy and San Babila Clinic, Healthy Aging Unit by Genomics and Biotechnology, Milano, Italy.
    Gopinath, Madhumala
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Murugesan, Ramachandran
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Zhang, Hong
    School of Medicine, Orebro University, Örebro, Sweden.
    B, Bhavani
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Girigoswami, Agnishwar
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Sollano, Jose
    Gastroenterology Department, University of Santo Tomas, Manila, The Philippines.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients2018In: Oncotarget, E-ISSN 1949-2553, Vol. 9, no 7, p. 7739-7748Article, review/survey (Refereed)
    Abstract [en]

    Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS. Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS, validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

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  • 91.
    Pathak, Surajit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. West China Hospital, Sichuan University, Chengdu, China.
    Zhang, Hong
    Örebro University, Örebro, Sweden.
    Gnosa, Sebastian
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Kumar Nandy, Suman
    Kalyani University, Kalyani, West Bengal, India.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Tafazzin protein expression is associated with tumorigenesis and radiation response in rectal cancer: a study of Swedish clinical trial on preoperative radiotherapy.2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 5, p. e98317-Article in journal (Refereed)
    Abstract [en]

    Background

    Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT.

    Methods

    140 rectal cancer patients were included in this study, of which 65 received RT before surgery and the rest underwent surgery alone. TAZ expression was determined by immunohistochemistry in primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In-silico protein-protein interaction analysis was performed to study the predictive functional interaction of TAZ with other oncoproteins.

    Results

    TAZ showed stronger expression in primary cancer and lymph node metastasis compared to distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ expression was significantly higher in stages I-III and non-mucinious cancer of non-RT patients. In RT patients, strong TAZ expression in biopsy was related to distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR, 6.160, 95% CI, 1.063–35.704). In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and FXYD-3.

    Conclusions

    Strong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.

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  • 92.
    Pfeifer, Daniella
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Xiao-Feng , Sun
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Survivin regulates expression of p73 isoforms TAp73 and ΔNp73 in colon cancer cell lines with and without γ-radiationManuscript (Other academic)
    Abstract [en]

    Wild type p53 represses expression of survivin, however little is known if survivin regulates p53 and the two isoforms of the p53 homologue p73, TAp73 and ΔNp73. The aim of our study was to investigate a possible connection between survivin and TAp73 and ΔNp73 in colon cancer cell lines HCT-116p53+/+ and HCT- 116p53-/- with and without γ-irradiation. HCT-116p53+/+ and HCT-116p53-/- were transfected with either survivin cDNA or siRNA against survivin. Cells transfected with siRNA were irradiated with 0Gy or 4Gy γ-irradiation to induce DNA-damage. Expression levels of survivin, TAp73, ΔNp73, mRNA and protein, and p53 protein was measured by RT-PCR and Western blot. Apoptosis was measured by means of M30- Apoptosense™ Elisa. Over-expression of survivin did not significantly change TAp73 or ΔNp73 mRNA and protein, whilst wild type p53 decreased. When survivin was knocked down, mRNA and protein of TAp73 and ΔNp73 decreased, both with and without γ-irradiation. Knockdown of survivin increased apoptosis in both HCT-116 cell lines with and without γ-irradiation. Knockdown of survivin decreased levels of TAp73 and ΔNp73 in both HCT-116p53+/+ and HCT-116p53-/-, and caused an increase in apoptosis, especially noticeable in HCT-116p53-/- after irradiation. Survivin down-regulation did not seem to affect the levels of wild type p53, whilst an up-regulation of survivin down-regulated wild type p53.

  • 93.
    Pfeifer, Daniella
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Polymorphism of the p73 gene in relation to colorectal cancer risk and survival2005In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 26, no 1, p. 103-107Article in journal (Refereed)
    Abstract [en]

    The results regarding a GC/AT polymorphism in the p73 gene in relation to cancer risk are inconsistent, and the significance of loss of heterozygosity (LOH) of the gene is unclear. In the present study, we investigated whether this polymorphism was related to the risk of colorectal cancer, and whether there were relationships between the polymorphism and LOH, protein expression or clinicopathological variables. 179 patients with colorectal cancer and 260 healthy controls were genotyped for the polymorphism by PCR-restriction fragment length polymorphism (RFLP). Fifty informative cases were examined for LOH in tumours. Immunohistochemistry was performed on distant (n = 42) and adjacent normal mucosa (n = 33), primary tumour (n = 6 9) and lymph node metastasis (n = 12). The frequencies of the genotypes were 63% for wild-type (GC/GC), 30% for heterozygotes (GC/AT) and 7% for variants (AT/AT) in patients, and 62, 36 and 2% in controls, respectively. The frequencies of the genotypes in the patients and controls were significantly different (P = 0.02). The patients carrying the AT allele had a better prognosis than those with the GC/GC genotype (OR = 0.42, 95% CI = 1.15-5.02, P = 0.02). No LOH was observed at the p73 locus. Expression of p73 protein was increased from normal mucosa to primary tumours (P = 0.02), but was not significantly changed between primary tumours and metastases (P = 1.0). In conclusion, the AT/AT homozygotes may have a greater risk of developing colorectal cancer, while the patients who carried the AT allele had a better prognosis.

  • 94.
    Pfeifer, Daniella
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Gao, Jingfang
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy2006In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, no 4, p. 1143-1148Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers.

    Methods and Materials: p73 was immunohistochemically examined on biopsies (unirradiated, n = 102), distant (from the large bowel, n = 82), and adjacent (adjacent to primary tumor, n = 89) normal mucosa samples, primary tumors (n = 131), and lymph node metastasis (n = 32) from rectal cancer patients participating in a clinical trial of preoperative RT. Seventy-four patients received surgery alone and 57 received additional RT.

    Results: Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (p ≤ 0.0001). Nuclear (p = 0.02) and cytoplasmic (p = 0.003) p73 was higher in irradiated distant mucosa samples than in unirradiated ones, and nuclear p73 tended to be increased in irradiated primary tumors compared with unirradiated ones (p = 0.06). p73 was positively related to cyclooxygenase-2 expression in irradiated tumors (p = 0.03). p73-negative tumors tended to have a lower local recurrence after RT compared with unirradiated cases (p = 0.06).

    Conclusions: Normal epithelial cells seem more sensitive to RT than tumor cells regarding p73 expression. Patients with p73-negative rectal tumors may have a lower risk of local recurrence after RT.

  • 95.
    Pfeifer, Daniella
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Wallin, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells with mutant p532009In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 135, no 11, p. 1583-1592Article in journal (Refereed)
    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.

     

  • 96.
    Pham, Tuan D.
    et al.
    Center for Artificial Intelligence, Prince Mohammad Bin Fahd University, Khobar, Saudi Arabia.
    Fan, Chuanwen
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Zhang, Hong
    Department of Medical Sciences, Örebro University, Örebro, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Artificial intelligence-based 5-year survival prediction and prognosis of DNp73 expression in rectal cancer patients2020In: CLINICAL AND TRANSLATIONAL MEDICINE, ISSN 2001-1326, Vol. 10, no 4, article id e159Article in journal (Other academic)
    Abstract [en]

    n/a

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  • 97.
    Pham, Tuan D.
    et al.
    Center for Artificial Intelligence, Prince Mohammad Bin Fahd University, Khobar 34754, Saudi Arabia.
    Ravi, Vinayakumar
    Center for Artificial Intelligence, Prince Mohammad Bin Fahd University, Khobar 34754, Saudi Arabia.
    Luo, Bin
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Sichuan Provincial People's Hospital, China.
    Fan, Chuanwen
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Artificial intelligence fusion for predicting survival of rectal cancer patients using immunohistochemical expression of Ras homolog family member B in biopsy2023In: Exploration of Targeted Anti-tumor Therapy, E-ISSN 2692-3114, Vol. 4, no 1, p. 1-16Article in journal (Refereed)
    Abstract [en]

    Aim: The process of biomarker discovery is being accelerated with the application of artificial intelligence (AI), including machine learning. Biomarkers of diseases are useful because they are indicators of pathogenesis or measures of responses to therapeutic treatments, and therefore, play a key role in new drug development. Proteins are among the candidates for biomarkers of rectal cancer, which need to be explored using state-of-the-art AI to be utilized for prediction, prognosis, and therapeutic treatment. This paper aims to investigate the predictive power of Ras homolog family member B (RhoB) protein in rectal cancer.

    Methods: This study introduces the integration of pretrained convolutional neural networks and support vector machines (SVMs) for classifying biopsy samples of immunohistochemical expression of protein RhoB in rectal-cancer patients to validate its biologic measure in biopsy. Features of the immunohistochemical expression images were extracted by the pretrained networks and used for binary classification by the SVMs into two groups of less and more than 5-year survival rates.

    Results: The fusion of neural search architecture network (NASNet)-Large for deep-layer feature extraction and classifier using SVMs provided the best average classification performance with a total accuracy = 85%, prediction of survival rate of more than 5 years = 90%, and prediction of survival rate of less than 5 years = 75%.

    Conclusions: The finding obtained from the use of AI reported in this study suggest that RhoB expression on rectal-cancer biopsy can be potentially used as a biomarker for predicting survival outcomes in rectal-cancer patients, which can be informative for clinical decision making if the patient would be recommended for preoperative therapy.

  • 98. Salahshor, S
    et al.
    Hou, H
    Diep, CB
    Loukala, A
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Liu, T
    Chen, J
    Iselius, L
    Rubio, C
    Lothe, RA
    Aaltonen, L
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Lindmark, G
    Lindblom, A
    A germline E-cadherin mutation in a family with gastric and colon cancer.2001In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 8, p. 439-443Article in journal (Refereed)
  • 99.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patientsManuscript (preprint) (Other academic)
    Abstract [en]

    CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells.

    Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data.

    CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007).

    The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.

  • 100.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Elkarim, Rihab
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer2014In: Cancer Microenvironment, ISSN 1875-2292, E-ISSN 1875-2284, Vol. 7, no 1, p. 61-69Article in journal (Refereed)
    Abstract [en]

    The scavenger receptor, CD163, is a macrophage-specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression as a macrophage trait in cancer cells, and macrophage infiltration and its clinical significance in colorectal cancer. Immunostaining of CD163 and macrophage infiltration were evaluated in paraffin-embedded specimens, earlier analyzed for CD31, D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 75 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 expression was positive in cancer cells in 20 % of colorectal cancer patients and was related to advanced tumor stages (P = 0.008) and unfavorable prognosis (p = 0.001). High macrophage infiltration was related to shorter survival and positive CD163 expression in tumor cells. The prognostic impact of macrophage infiltration was independent of tumor stage and CD163 expression in cancer cells (p = 0.034). The expression of macrophage phenotype in colorectal cancer cells is associated with macrophage density in tumor stroma and lower survival rates. Macrophage infiltration has an independent prognostic impact on mortality in colorectal cancer. In accordance with previous experimental studies, these findings provide new insights into the role of macrophages in colorectal cancer.

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