liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 10 of 10
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Gao, Jingfang
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Pfeifer, Daniella
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    He, Lu-Jun
    Qiao, Fang
    Zhang, Zhiyong
    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.
    Wang, Zhen-Lei
    Jia, Cun-Rong
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    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.
    Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 3, p. 345-350Article in journal (Refereed)
    Abstract [en]

    Objective. The inhibitory proteins, IκBs, regulate the activity of nuclear factor kappa-beta (NF-κB), which is implicated in tumorigenesis by regulating expression of a variety of genes involved in cellular transformation, proliferation, invasion, angiogenesis and metastasis. Variants in the genes encoding IκBs may be involved in cancer development through the activation of NF-κB. The objective of this study was to investigate the susceptibility of an A to G variation (rs696) in the 3′ UTR of NFKBIA (encoding IκBα) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC patients. Material and methods. A case-control study was carried out on a Swedish (155 CRCs, 438 controls) and a Chinese population (199 CRCs, 577 controls). The genotype of NFKBIA was determined by PCR-restriction fragment length polymorphism. Results. The frequency of the AG genotype was increased in the Chinese patients ≥50 years of age compared with the Chinese controls (odds ratio (OR) = 3.06, 95% confidence interval (CI) = 1.55-6.02, p=0.001), even when adjusted for age (OR = 3.20, 95% CI = 1.61-6.38, p=0.001). The GG genotype of NFKBIA was related to a poorer survival rate in the Swedish patients, independent of gender, age, tumour location, Dukes' stage and differentiation (hazard ratio = 3.10, 95% Cl = 1.28-7.60, p=0.01). Conclusions. Chinese individuals ≥50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients. © 2007 Taylor & Francis.

  • 2.
    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.

  • 3.
    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.

  • 4.
    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.
    Sun, X-F
    University of Skovde.
    Zhang, H
    University of Skovde.
    PLAYS AND IMPORTANT ROLE IN THE CISPLATIN TREATMENT FOR COLORECTAL CANCER in ANNALS OF ONCOLOGY, vol 21, issue , pp I39-I392010In: ANNALS OF ONCOLOGY, Oxford University Press , 2010, Vol. 21, p. I39-I39Conference paper (Refereed)
    Abstract [en]

    n/a

  • 5.
    Pfeifer, Daniella
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    p73 in colorectal cancer2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Colorectal cancer (CRC) is the third most common cancer in the world, with about 5000 new cases in Sweden every year. CRC is caused by mutation (inherited or acquired) in genes, by gene variants and changed expression of proteins. The primary way to achieve a curative result for CRC is to remove the tumor by surgery. To reduce risk of recurrence chemo- or radiotherapy are given as a complement to surgery. p73 is a structural and functional homologue of tumor suppressor p53. However, p73 is rarely mutated in tumors, but rather overexpressed as compared to normal tissue. There are two main isoforms of p73, the transactivation capable TAp73 and the truncated ΔNp73, which are involved in an autoregulatory loop with TAp73 and p53.

    The aim of this study was to investigate the role of p73 and related proteins in the development and treatment of CRC. A G4C14-to-A4T14 polymorphism of p73 was studied in CRC patients and healthy controls (Paper I), and rectal cancer patients who were randomized to treatment with either surgery alone or preoperative radiotherapy and surgery (Paper II). The AT/AT genotype of the p73 polymorphism may increase risk of CRC development and CRC patients with the AT allele had a better prognosis. When dividing the cases into colon and rectal cancer it was seen that in colon cancer the AT allele tended to be more favorable for overall survival, while in rectal cancer the GC allele seemed to be more favorable. Rectal cancer patients, with a combination of GC/GC genotype, wild type p53 and weak survivin expression survived longer after preoperative radiotherapy. This was not observed in the patients only receiving surgery. The protein expression of p73 was further studied in the rectal cancer patients randomized to treatment with either surgery alone or preoperative radiotherapy and surgery (Paper III). p73 was expressed higher in tumor tissue than in normal mucosa. Patients with p73 negative tumors had a lower risk of local recurrence after radiotherapy, as opposed to patients that had p73 positive tumors or patients with p73 negative tumors that did not receive radiotherapy. Effects of γ-radiation was further studied in colon cancer cell lines KM12C, KM12SM and KM12L4a regarding cell cycle, survival fraction (clonogenicity), apoptosis and protein expression patterns of mutated p53, TAp73, ΔNp73, survivin and PRL-3 (Paper IV). KM12C displayed low survival fraction, low apoptosis, no cell cycle arrest and an upregulation of the antiapoptotic ΔNp73 after irradiation. KM12L4a showed a high survival fraction, but high apoptosis, arresting of the cell cycle and upregulation of the radio-resistance factor survivin. The effects of overexpression and knockdown of survivin on TAp73, ΔNp73 and p53 expression in colon cancer cell lines HCT-116p53+/+ and HCT-116p53-/- with and without γ-radiation were studied (Paper V). Overexpression of survivin decreased wild type p53, whilst downregulation of survivin lead to a simultaneous downregulation of TAp73 and ΔNp73, mRNA and protein, both with and without γ- radiation. Knockdown of survivin also demonstrated an increase in apoptosis.

    In conclusion, we showed that the G4C14-to-A4T14 polymorphism of p73 and p73 protein expression may be involved in CRC development, radiotherapy response and survival. We further showed that TAp73, ΔNp73 and p53 were regulated by survivin in colon cancer cells.

    List of papers
    1. Polymorphism of the p73 gene in relation to colorectal cancer risk and survival
    Open this publication in new window or tab >>Polymorphism of the p73 gene in relation to colorectal cancer risk and survival
    2005 (English)In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 26, no 1, p. 103-107Article in journal (Refereed) Published
    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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18428 (URN)10.1093/carcin/bgh305 (DOI)15485994 (PubMedID)
    Available from: 2009-05-26 Created: 2009-05-26 Last updated: 2017-12-13Bibliographically approved
    2. Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy
    Open this publication in new window or tab >>Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy
    2009 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 92, no 2, p. 215-220Article in journal (Refereed) Published
    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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18429 (URN)10.1016/j.radonc.2009.06.007 (DOI)
    Note
    Original Publication: Jasmine Lööf, Daniella Pfeifer, Gunnar Adell and Xiao-Feng Sun, Significance of an exon 2 G4C14-to-A4T14 polymorphism in the p73 gene on survival in rectal cancer patients with or without preoperative radiotherapy, 2009, Radiotherapy and Oncology, (92), 2, 215-220. http://dx.doi.org/10.1016/j.radonc.2009.06.007 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Available from: 2009-09-09 Created: 2009-05-26 Last updated: 2017-12-13Bibliographically approved
    3. Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy
    Open this publication in new window or tab >>Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy
    2006 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 65, no 4, p. 1143-1148Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Elsevier, 2006
    Keywords
    p73; Radiotherapy; Local recurrence; Rectal cancer; Immunohistochemistry
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18430 (URN)10.1016/j.ijrobp.2006.02.028 (DOI)16750334 (PubMedID)
    Available from: 2009-05-26 Created: 2009-05-26 Last updated: 2017-12-13Bibliographically approved
    4. Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells with mutant p53
    Open this publication in new window or tab >>Protein expression following gamma-irradiation relevant to growth arrest and apoptosis in colon cancer cells with mutant p53
    2009 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 135, no 11, p. 1583-1592Article in journal (Refereed) Published
    Abstract [en]

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

     

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-14786 (URN)10.1007/s00432-009-0606-4 (DOI)
    Available from: 2008-09-24 Created: 2008-09-24 Last updated: 2017-12-13Bibliographically approved
    5. Survivin regulates expression of p73 isoforms TAp73 and ΔNp73 in colon cancer cell lines with and without γ-radiation
    Open this publication in new window or tab >>Survivin regulates expression of p73 isoforms TAp73 and ΔNp73 in colon cancer cell lines with and without γ-radiation
    (English)Manuscript (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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18431 (URN)
    Available from: 2009-05-26 Created: 2009-05-26 Last updated: 2010-01-14Bibliographically approved
  • 6.
    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.

  • 7.
    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.

  • 8.
    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.

  • 9.
    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.

     

  • 10.
    Yang, Lie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Olsson, Birgit
    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.
    Jönsson, J-I
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zhou, Z-G
    Sichuan University.
    Jiang, X
    Sichuan University.
    Fredriksson, Bengt-Arne
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Zhang, H
    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.
    Knockdown of peroxisome proliferator-activated receptor-beta induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells2010In: ONCOGENE, ISSN 0950-9232, Vol. 29, no 4, p. 516-526Article in journal (Refereed)
    Abstract [en]

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

1 - 10 of 10
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf