| 1. |
- Ahnström, Marie, et al.
(författare)
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Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer
- 2009
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 34:2, s. 441-448
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Tidskriftsartikel (refereegranskat)abstract
- Cyclin E and the retinoblastoma protein (Rb) are both important regulators of the G(1) phase in the cell cycle. Overexpression of cyclin E and lost expression of Rb has previously been observed in breast tumours at frequencies of 10-50% and 20-30%, respectively. We explored the prognostic role of cyclin E and Rb in breast cancer patients randomised for tamoxifen (TAM), CMF (cyclophosphamide, metotrexate, 5-fluorouracil) chemotherapy and radiotherapy (RT) and how their expression affects the patients response to treatment. Protein expression was assessed with immunohistochemistry. We found overexpression of cyclin E in 32.1% (71/221) of the tumours and loss of Rb expression in 25.0% (59/236). Increased expression of cyclin E correlated to dysfunctional p53 (P=0.003) while loss of Rb correlated to normal p53 status (P=0.001). Our results suggest that patients with high cyclin E tumours have less benefit from tamoxifen (ER+, TAM vs. no TAM; RR=0.97; 95% CI, 0.36-2.60) than patients whose tumours show low expression (ER+, TAM vs. no TAM; RR =0.41; 95% CI, 0.24-0.72). Cyclin E also tended to predict the benefit from radiotherapy with a local recurrence rate of 0.31 (RT vs. CMF; 95% CI, 0.12-0.93) for patients with low expression and 0.68 (RT vs. CMF; 95% CI, 0.2-2.32) for patients with high expression of cyclin E. When the p53 status was taken in consideration the results showed that patients with both normal p53 and normal Rb expression had considerably lower locoregional recurrence rate when treated with radiotherapy instead of CMF (RR=0.17; 95% CI, 0.052-0.58) as compared to patients with either altered Rb or p53 or both (RR=0.70; 95% CI, 0.28-1.73).
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| 2. |
- Au, Gough G, et al.
(författare)
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Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21.
- 2005
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 26:6, s. 1471-6
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Tidskriftsartikel (refereegranskat)abstract
- Cultured melanoma cell lines despite exhibiting similar in vitro morphology, display significant phenotypic and growth rate differences when propagated as in vivo xenografts. Previously we have shown that Coxsackievirus A21 (CVA21) lytically infects in vitro cultures of malignant melanoma cells and is efficient at reducing the tumor burden of mice bearing slow-growing SK-Mel-28 melanoma xenografts. The oncolytic activity of CVA21 against in vivo melanoma xenografts, which possess rapid growth rates and more extensive vascular structure than SK-Mel-28 xenografts warrants further investigation. In the present study we evaluated the oncolytic action of CVA21 against rapidly growing melanoma xenografts (ME4405) which exhibit a highly vascular phenotype. Flow cytometric analysis indicated that in vitro cultures of ME4405 cells expressed comparable levels of the CVA21 cellular receptors, ICAM-1 (intercellular adhesion molecules-1) and DAF (decay accelerating factor) to SK-Mel-28 cells. Despite similar levels of CVA21 receptor expression, SK-Mel-28 cells appear to be more susceptible to viral lysis than ME4405 cells, even though the kinetics of virus replication in both lines was comparable. Intratumoral, intraperitoneal or intravenous administration of CVA21 were equally effective in reducing the tumor volume of ME4405 xenografts in immunodeficient mice, and provides further evidence for the use of CVA21 as a novel oncolytic agent against varying phenotypes of malignant melanoma.
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| 3. |
- Belpomme, D., et al.
(författare)
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The growing incidence of cancer : Role of lifestyle and screening detection (Review)
- 2007
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 30:5, s. 1037-1049
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Forskningsöversikt (refereegranskat)abstract
- The increasing incidence of a variety of cancers after the Second World War confronts scientists with the question of their origin. In Western countries, expansion and ageing of the population, as well as progress in cancer detection using new diagnostic and screening tests cannot fully account for the observed growing incidence of cancer. Our hypothesis is that environmental factors play a more important role in cancer genesis than it is usually agreed: i) over the last 2-3 decades, alcohol consumption and tobacco smoking in men have significantly decreased; ii) obesity is increasing in many countries, but the growing incidence of cancer also concerns cancers not related to obesity nor to other lifestyle-related factors; iii) there is evidence that the environment has changed over the same time scale as the recent rise in cancer incidence, and that this change included the accumulation of many new carcinogenic factors in the environment; iv) genetic susceptibility to cancer due to genetic polymorphism cannot have changed over one generation and actually favours the role of exogenous factors through gene-environment interactions; v) age is not the unique factor to be considered since the rising incidence of cancers is seen across all age categories, including children; vi) the fetus is specifically vulnerable to exogenous factors. A fetal exposure during a critical window period may explain why current epidemiological studies may be negative in adults. We therefore propose that the involuntary exposure to many carcinogens in the environment contributes to the rising trend in cancer incidence.
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| 4. |
- Benetkiewicz, Magdalena, et al.
(författare)
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Chromosome 22 array-CGH profiling of breast cancer delimited minimal common regions of genomic imbalances and revealed frequent intra-tumoral genetic heterogeneity
- 2006
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 29:4, s. 935-945
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a common malignancy and the second most frequent cause of death among women. Our aim was to perform DNA copy number profiling of 22q in breast tumors using a methodology which is superior, as compared to the ones applied previously. We studied 83 biopsies from 63 tumors obtained from 60 female patients. A general conclusion is that multiple distinct patterns of genetic aberrations were observed, which included deletion(s) and/or gain(s), ranging in size from affecting the whole chromosome to only a few hundred kb. Overall, the analysis revealed genomic imbalances of 22q in 22% (14 out of 63) of tumors. The predominant profile (11%) was monosomy 22. The smallest identified candidate region, in the vicinity of telomere of 22q, encompasses approximately 220 kb and was involved in all but one of the tumors with aberrations on chromosome 22. This segment is dense in genes and contains 11 confirmed and one predicted gene. The availability of multiple biopsies from a single tumor provides an excellent opportunity for analysis of possible intra-tumor differences in genetic profiles. In 15 tumors we had access to two or three biopsies derived from the same lesion and these were studied independently. Four out of 15 (26.6%) tumors displayed indications of clonal intra-tumor genotypic differences, which should be viewed as a high number, considering that we studied in detail only a single human chromosome. Our results open up several avenues for continued genetic research of breast cancer.
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| 5. |
- Boldrup, Linda, et al.
(författare)
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Expression of p63, COX-2, EGFR and beta-catenin in smokers and patients with squamous cell carcinoma of the head and neck reveal variations in non-neoplastic tissue and no obvious changes in smokers.
- 2005
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 27:6, s. 1661-1667
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Tidskriftsartikel (refereegranskat)abstract
- Squamous cell carcinoma of the head and neck (SCCHN), the 6th most common malignancy in the world, is associated with smoking and has a low 5-year survival rate. Various changes have been described at different stages of SCCHN tumour development, including overexpression of p63, a protein important for development of normal epidermal structures. p63 has been suggested to activate beta-catenin, and nuclear accumulation of beta-catenin is an important event in many cancers. Elevated COX-2 activity and overexpression of EGFR protein has been shown in a variety of human cancers, including SCCHN. An important question for the pathogenesis of SCCHN is when the genetic changes take place during the natural course of the disease, and whether they appear in clinically normal oral mucosa to predispose tumour development. We mapped the expression of p63, COX-2, EGFR, beta-catenin, and PP2A in oral mucosa from smokers/non-smokers and from patients with SCCHN. We also considered if changes occurring in tumours are present in the clinically normal tissue adjacent to the tumour. No direct influence of heavy smoking on the levels of the proteins studied could be seen. Tumours and clinically normal non-neoplastic tissue from SCCHN patients showed increased expression of COX-2 and PP2A. Interestingly, non-neoplastic tissue adjacent to SCCHN also showed increased beta-catenin, although this was not seen in tumours. The data support the notion that pre-existing alterations in clinically normal epithelium exist in patients with SCCHN and could be important for the pathogenesis of the disease and for local recurrences.
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| 6. |
- Cui, Baoxia, et al.
(författare)
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Mutation of PIK3CA : possible risk factor for cervical carcinogenesis in older women
- 2009
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 34:2, s. 409-416
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Tidskriftsartikel (refereegranskat)abstract
- PIK3CA encodes the p110alpha catalytic subunit of PI 3-kinase, which regulates signaling pathways important for neoplasia, cell proliferation and apoptosis. Somatic mutations in this gene have been detected in several solid human tumors. We investigated these mutations in cervical carcinoma and its precursors, and their association with HPV infection and patient clinical data. The mutations were analyzed using post-PCR direct genomic DNA sequencing. Samples included 9 cervical cancer cell lines, 184 invasive cervical carcinomas, and 30 cervical neoplasias. Missense mutations of PIK3CA were identified in 15/184 (8.15%) invasive cervical carcinomas. One novel mutation G1638C (Q546H) was found. Three mutations were identified in the cervical cancer lines. No mutations were found in the precursors. The difference in mutation frequency between invasive and pre-invasive lesions was not significant (p=0.1372). In relation to age and HPV, the mutation rate was significantly higher in patients>or=60 years (p=0.001), while the rate of HPV infection was higher in patients
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| 7. |
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| 10. |
- Ekberg, Thomas, et al.
(författare)
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Expression of EGFR, HER2, HER3, and HER4 in metastatic squamous cell carcinomas of the oral cavity and base of tongue
- 2005
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 26:5, s. 1177-85
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Tidskriftsartikel (refereegranskat)abstract
- The expressions of all four receptors in the epidermal growth factor receptor family, EGFR. HER2, HER3, and HER4 were evaluated by immunohistochemistry in 19 cases of metastatic squamous cell carcinoma of the oral cavity and base of tongue. EGFR had a similar and high expression in both primary tumours and the corresponding metastases, while the expression in normal epithelium was lower in most cases. HER2 was not expressed to the same extent as EGFR. However, when HER2 was well expressed, it was in most cases expressed to the same extent and intensity in the primary tumours, metastases, and normal epithelium. The expression of HER3 and HER4 varied and was mainly cytoplasmic in all cases studied. No overexpression of HER3 and HER4 in tumours was seen as compared to normal epithelium. In order to further investigate the distribution of HER3, two HER3 expressing cell lines originating from tongue cancer were analysed in vitro, using radiolabelled anti-HER3 antibodies directed to the extracellular domains of the receptor. The results indicated that HER3 was not present in measurable amounts in the cellular membrane. There is a need for improved diagnostics and therapy for the studied type of tumours, e.g. using radiolabelled antibodies or ligands, and EGFR seemed suitable as target since the expression was high, membrane associated and similar in the primary tumours and the corresponding metastases.
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