| 81. |
- Lomnytska, M. I., et al.
(författare)
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Differential expression of ANXA6, HSP27, PRDX2, NCF2, and TPM4 during uterine cervix carcinogenesis : diagnostic and prognostic value
- 2011
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 104:1, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Background:Cytology-based diagnostics of squamous cervical cancer (SCC) precursor lesions is subjective and can be improved by objective markers.Methods:IHC-based analysis of ANXA6, HSP27, peroxiredoxin 2 (PRDX2), NCF2, and tropomyosin 4 (TPM4) during SCC carcinogenesis.Results:Expression of ANXA6, HSP27, PRDX2, and NCF2 in the cytoplasm of dysplastic cells increased from cervical intraepithelial neoplasia 2/3 (CIN2/3) to microinvasive cancer. Invasive SCC showed lower expression of TPM4 than CIN and normal epithelium. CIN2/3 with the highest sensitivity and specificity differed from normal epithelium by cytoplasmic expression of HSP27. Patients with cytoplasmic HSP27 expression in SCC deviating from that observed in normal epithelium had worse relapse-free (P0.019) and overall (P0.014) survival. Invasive SCC with the highest sensitivity and specificity differed from normal epithelium by expression of PRDX2 and TPM4 in the cytoplasm, from CIN2/3 by the expression of ANXA6 and TPM4 in the cytoplasm, and from microinvasive SCC by the expression of PRDX2 and ANXA6 in the cytoplasm. The number of sporadic ANXA6 cells between the atypical cells increased from CIN2/3 to invasive SCC.Conclusion:Detection of expression changes of the proteins ANXA6, HSP27, PRDX2, NCF2, and TPM4 in SCC precursor lesions may aid current cytological and pathological diagnostics and evaluation of prognosis.
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| 82. |
- Lomnytska, M. I., et al.
(författare)
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Impact of genomic stability on protein expression in endometrioid endometrial cancer
- 2012
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106:7, s. 1297-1305
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genomic stability is one of the crucial prognostic factors for patients with endometrioid endometrial cancer (EEC). The impact of genomic stability on the tumour tissue proteome of EEC is not yet well established.METHODS: Tissue lysates of EEC, squamous cervical cancer (SCC), normal endometrium and squamous cervical epithelium were subjected to two-dimensional (2D) gel electrophoresis and identification of proteins by MALDI TOF MS. Expression of selected proteins was analysed in independent samples by immunohistochemistry.RESULTS: Diploid and aneuploid genomically unstable EEC displayed similar patterns of protein expression. This was in contrast to diploid stable EEC, which displayed a protein expression profile similar to normal endometrium. Approximately 10% of the differentially expressed proteins in EEC were specific for this type of cancer with differential expression of other proteins observed in other types of malignancy (e.g., SCC). Selected proteins differentially expressed in 2D gels of EEC were further analysed in an EEC precursor lesion, that is, atypical hyperplasia of endometrium, and showed increased expression of CLIC1, EIF4A1 and PRDX6 and decreased expression of ENO1, ANXA4, EMD and Ku70.CONCLUSION: Protein expression in diploid and aneuploid genomically unstable EEC is different from the expression profile of proteins in diploid genomically stable EEC. We showed that changes in expression of proteins typical for EEC could already be detected in precursor lesions, that is, atypical hyperplasia of endometrium, highlighting their clinical potential for improving early diagnostics of EEC.
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| 83. |
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| 84. |
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| 85. |
- Ludvigsson, Jonas F., 1969-, et al.
(författare)
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Risk of prostate cancer in a population-based cohort of men with coeliac disease
- 2012
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Ingår i: British Journal of Cancer. - London, United Kingdom : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:1, s. 217-221
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer (PC) is a leading cause of fatal cancer in men in developed countries. Coeliac disease (CD) has previously been linked to a raised cancer risk, and changes in some exposures following a CD diagnosis might hypothetically raise PC risk.Methods: We identified 10 995 patients with CD who had undergone a small intestinal biopsy in 1969-2007. Statistics Sweden then identified 54 233 age-matched male reference individuals from the general population. PC data were obtained from the Swedish Cancer Register. Hazard ratios (HRs) for PC were estimated using Cox regression analysis.Results: During follow-up, 185 individuals with CD (expected = 200) had an incident diagnosis of PC. This corresponds to a HR of 0.92 (0.79-1.08) (with 95% confidence interval) and an absolute risk reduction of 15/100 000 person-years among those with CD. An increased risk was not observed even when identification of PC began 5 years after biopsy.Conclusion: Our conclusion is that a CD diagnosis does not represent an increased risk for PC.
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| 86. |
- Lundin, Kristina, et al.
(författare)
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Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.
- 2011
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 105:11, s. 1676-1683
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Tidskriftsartikel (refereegranskat)abstract
- Background:The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.Methods:In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.Results:Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with three diplotypes in each. Patients in group B had larger total breast volume (P=0.024), higher body mass index (BMI) (P=0.050), more axillary lymph node involvement (P(trend)=0.020), and higher histological grade (P(trend)=0.031). There were 59 breast cancer events in the 569 patients with invasive cancers and no preoperative treatment. Patients in group B also had shorter disease-free survival (P=0.037) than patients in group A. Among patients in group B with oestrogen receptor α positive tumours, tamoxifen (TAM) treatment was associated with longer disease-free survival (P=0.008), while treatment with aromatase inhibitors (AIs) was not (P=0.94). Response to endocrine treatment could not be predicted based on BMI, suggesting that the effect of AR diplotypes went beyond that of a higher BMI.Conclusion:A marker for a group of patients who responded to TAM, but not to AIs, was identified. If this finding is confirmed, AR genotyping may provide useful information for selection of endocrine treatment of breast cancer patients.British Journal of Cancer advance online publication, 27 October 2011; doi:10.1038/bjc.2011.441 www.bjcancer.com.
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| 87. |
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| 88. |
- Martin-Liberal, J., et al.
(författare)
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Phase I study and preclinical efficacy evaluation of the mTOR inhibitor sirolimus plus gemcitabine in patients with advanced solid tumours
- 2014
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:5, s. 858-865
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Tidskriftsartikel (refereegranskat)abstract
- Background: We conducted a phase I study in patients with advanced solid tumours to identify the recommended dose, assess pharmacokinetics (PK), pharmacodynamic activity and preclinical antitumour efficacy of the combination of sirolimus and gemcitabine. Methods: Nineteen patients were treated with sirolimus 2 or 5mg daily and gemcitabine 800 or 1000 mg m(-2) on days 1 and 8. Dose escalation depended on dose-limiting toxicity (DLT) rate during the first 3-week period. Paired skin biopsies were evaluated for phosphorylated S6 (pS6) as marker of mTOR (mammalian target of rapamycin) inhibition. Pharmacokinetics and preclinical evaluation of efficacy using two different sarcoma cell lines and leiomyosarcoma xenografts were also conducted. Results: Three DLTs were observed: grade 3 transaminitis, grade 3 thrombocytopenia and grade 4 thrombocytopenia. Common treatment-related adverse events included anaemia, neutropenia, thrombocytopenia and transaminitis. Pharmacodynamic analyses demonstrated mTOR inhibition with sirolimus 5mg and PK showed no influence of sirolimus concentrations on gemcitabine clearance. In vitro and in vivo studies suggested mTOR pathway hyperactivation by gemcitabine that was reversed by sirolimus. Tumour growth in leiomyosarcoma xenografts was dramatically inhibited by the treatment. Conclusions: Recommended dose was sirolimus 5mg per 24 h plus gemcitabine 800 mg m(-2). Antitumour activity in preclinical sarcoma models and mTOR signalling inhibition were observed. A phase II study is currently ongoing.
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| 89. |
- Mehrara, Esmaeil, 1971, et al.
(författare)
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Objective assessment of tumour response to therapy based on tumour growth kinetics.
- 2011
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 105:5, s. 682-6
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Tidskriftsartikel (refereegranskat)abstract
- Current standards for assessment of tumour response to therapy (a) categorise therapeutic efficacy values, inappropriate for patient-specific and deterministic studies, (b) neglect the natural growth characteristics of tumours, (c) are based on tumour shrinkage, inappropriate for cytostatic therapies, and (d) do not accommodate integration of functional/biological means of therapeutic efficacy assessed with, for example, positron emission tomography or magnetic resonance imaging, with data from anatomical changes in tumour.
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| 90. |
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