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Molecular studies of radiotherapy and chemotherapy in colorectal cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro university , 2015. , 73 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 122
Keyword [en]
Colorectal cancer, Radiotherapy, Chemotherapy, p53, p73, PINCH, miRNAs
National Category
Medical Biotechnology
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-43635ISBN: 978-91-7529-070-6 (print)OAI: oai:DiVA.org:oru-43635DiVA: diva2:795383
Public defence
2015-05-29, Prismahuset, Hörsal 2, Örebro universitet, Fakultetsgatan 1, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Funder
Swedish Cancer SocietySwedish Research Council
Note

Funding Agency:

Health Research Council in the South-East of Sweden

Available from: 2015-03-16 Created: 2015-03-16 Last updated: 2015-12-21Bibliographically approved
List of papers
1. Impact of PINCH expression on survival in colorectal cancer patients
Open this publication in new window or tab >>Impact of PINCH expression on survival in colorectal cancer patients
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2011 (English)In: BMC Cancer, ISSN 1471-2407, Vol. 11, 103Article in journal (Refereed) Published
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% CI, 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% CI, 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.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-44356 (URN)10.1186/1471-2407-11-103 (DOI)000289146300001 ()21426571 (PubMedID)2-s2.0-79953094759 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research Council
Note

Funding Agency: Health and Research Council in the South-East of Sweden

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2015-04-20Bibliographically 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, 215-20 p.Article 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.

MATERIALS 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% had GC/AT and 4% had 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
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-44361 (URN)10.1016/j.radonc.2009.06.007 (DOI)19581013 (PubMedID)2-s2.0-67650992087 (Scopus ID)
Funder
Swedish Cancer Society
Note

Funding Agency: Health Research Council in the South-East of Sweden

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2015-04-20Bibliographically approved
3. Effects of ΔNp73β on cisplatin treatment in colon cancer cells
Open this publication in new window or tab >>Effects of ΔNp73β on cisplatin treatment in colon cancer cells
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2012 (English)In: Molecular Carcinogenesis, ISSN 0899-1987, E-ISSN 1098-2744, Vol. 51, no 8, 628-35 p.Article in journal (Refereed) Published
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, ΔNp73, which lacks the transactivation domain of the full length TAp73 protein. TAp73 is considered pro-apoptotic, and ΔNp73 anti-apoptotic. In this study, we overexpressed ΔNp73β 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 ΔNp73β 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 ΔNp73β-cells than mock-transfected cells. However, ΔNp73β overexpression did not affect the cellular susceptibility to cisplatin. In conclusion, the overexpression of ΔNp73β increases viability in p53 wild type and p53 mutant colon cancer cells, and cisplatin induces the degradation of ΔNp73β in a dose-dependent manner.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-44362 (URN)10.1002/mc.20835 (DOI)000305962400004 ()21837762 (PubMedID)2-s2.0-84863477921 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research Council
Note

Funding Agency: Health Research Council in the South-East of Sweden 

Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2015-04-20Bibliographically approved
4. Modification of microRNA expression profiles by oxaliplatin, p53 and p73 in human colon cancer cells in vitro
Open this publication in new window or tab >>Modification of microRNA expression profiles by oxaliplatin, p53 and p73 in human colon cancer cells in vitro
(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-44365 (URN)
Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2015-04-20Bibliographically approved

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