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Search Results: 1 - 10 of 2192 matches for " the Polish Ovarian Cancer Study Group (POCSG) "
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TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study
Jolanta Kupryjanczyk, Ewa Kraszewska, Izabela Ziolkowska-Seta, Radoslaw Madry, Agnieszka Timorek, Janina Markowska, Jerzy Stelmachow, Mariusz Bidzinski, the Polish Ovarian Cancer Study Group (POCSG)
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-27
Abstract: We compared the effectiveness of PC/PAC (n = 253) and TP (n = 199) with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+)] and without TP53 accumulation [TP53(-)].The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+), and not in the TP53(-) group. In the TP53(+) group taxane-platinum therapy enhanced the probability of complete remission (p = .018), platinum sensitivity (p = .014), platinum highly sensitive response (p = .038) and longer survival (OS, p = .008). Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+) group. In the TP53(-) group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010). However, in the TP53(-) group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077). Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation.Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+) tumors or older than 53 years. In the group of patients ≤53 yrs and with TP53(-) tumors platinum-based therapy is possibly equally efficient. We provide hints for planning randomized trials to verify these observations.First-line chemotherapy based on taxanes and platinum derivatives is a standard of care for ovarian cancer patients (taxane-platinum chemotherapy, TP) [1]; it replaced platinum-cyclophosphamide (PC) or other protocols of DNA damaging chemotherapy (PAC:
Nuclear survivin expression is a positive prognostic factor in taxane-platinum-treated ovarian cancer patients
Anna Felisiak-Golabek, Alina Rembiszewska, Iwona K Rzepecka, Lukasz Szafron, Radoslaw Madry, Magdalena Murawska, Tomasz Napiorkowski, Piotr Sobiczewski, Beata Osuch, Jolanta Kupryjanczyk, the Polish Ovarian Cancer Study Group (POCSG)
Journal of Ovarian Research , 2011, DOI: 10.1186/1757-2215-4-20
Abstract: Survivin and TP53 expression was evaluated immunohistochemically in 435 archival samples of ovarian carcinomas (244 patients were treated with platinum/cyclophosphamide-PC/PAC; 191-with taxane-platinum (TP) agents). Univariate and multivariate statistical analyses were performed in patients groups divided according to the administered chemotherapeutic regimen, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively).Nuclear and cytoplasmic survivin expression was observed in 92% and 74% of the carcinomas, respectively. In patients treated with TP, high nuclear survivin expression decreased the risk of disease recurrence and death, and increased the probability of high platinum sensitivity (p < 0.01), but only in the TP53(+) group, and not in the TP53(-) group.It appears that TP53 status determines the clinical importance of nuclear survivin expression in taxane-platinum treated ovarian cancer patients.Recently molecular anticancer therapies have undergone rapid development. Survivin, the smallest member of the family of the protein inhibitors of apoptosis (IAP) [1], is considered to be a potential target for molecular therapy [2]. Target survivin arose from data obtained from cancer cell lines, showing that survivin inhibition contributes to increased tumour response to various anticancer agents [3]. The results of clinical analyses are less consistent, as high survivin expression had been associated with both favourable and unfavourable prognosis [4].Ovarian cancer is the most lethal gynaecological malignancy. In the last decade, taxanes combined with cisplatin or its analogues (TP therapy) have been considered standard first-line treatment for ovarian cancer [5,6]. Although the introduction of taxanes has significantly improved treatment results, still 20% to 30% of the patients fail to achieve complete remission [6-8].Taxanes interact with β-tubulin and increase its polymerisation and stabilisation. In the presence of paclitaxel, cells
High resolution melting for mutation scanning of TP53 exons 5–8
Michael Krypuy, Ahmed Ahmed, Dariush Etemadmoghadam, Sarah J Hyland, Australian Ovarian Cancer Study Group, Anna deFazio, Stephen B Fox, James D Brenton, David D Bowtell, Alexander Dobrovic
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-168
Abstract: We designed PCR amplicons for HRM mutation scanning of TP53 exons 5 to 8 and tested them with DNA from cell lines hemizygous or homozygous for known mutations. We assessed the sensitivity of each PCR amplicon using dilutions of cell line DNA in normal wild-type DNA. We then performed a blinded assessment on ovarian tumour DNA samples that had been previously sequenced for mutations in TP53 to assess the sensitivity and positive predictive value of the HRM technique. We also performed HRM analysis on breast tumour DNA samples with unknown TP53 mutation status.One cell line mutation was not readily observed when exon 5 was amplified. As exon 5 contained multiple melting domains, we divided the exon into two amplicons for further screening. Sequence changes were also introduced into some of the primers to improve the melting characteristics of the amplicon. Aberrant HRM curves indicative of TP53 mutations were observed for each of the samples in the ovarian tumour DNA panel. Comparison of the HRM results with the sequencing results revealed that each mutation was detected by HRM in the correct exon. For the breast tumour panel, we detected seven aberrant melt profiles by HRM and subsequent sequencing confirmed the presence of these and no other mutations in the predicted exons.HRM is an effective technique for simple and rapid scanning of TP53 mutations that can markedly reduce the amount of sequencing required in mutational studies of TP53.p53 is a tumour suppressor that plays a major role in regulating the cellular response to environmental and genotoxic stress, through cell cycle inhibition and promotion of programmed cell death or senescence [1-4]. There are a variety of stresses that have been shown to activate p53 including DNA damage, cell-cycle aberrations, hypoxia, and aberrant growth signals resulting from expression of oncogenes [5-10]. Moreover, a wide body of work has established the role of p53 in response to DNA damage [5-8].It has been estimated that th
Hormone Replacement Therapy after Prophylactic Adnexectomy
Pascale This, Rémy J Salmon, Sylvie Dolbeault, Anne de la Rochefordière, Brigitte Sigal-Zafrani, Dominique Stoppa-Lyonnet, the Institut Curie Breast and Ovarian Cancer Risk Study Group
Hereditary Cancer in Clinical Practice , 2005, DOI: 10.1186/1897-4287-3-4-181
Abstract: At the Curie Institute, we take into account the preferences of women after they have been thoroughly informed:1. We recommend PA to women at 40 years of age if they have a BRCA1 mutation, or a BRCA2 mutation and a family history of ovarian cancer, and at 50 years of age if they have a BRCA2 mutation without a family history of ovarian cancer.2. In women unaffected by breast cancer, we give very complete information on the benefits and risks of HRT and alternatives, such as symptomatic treatments for hot flushes, vaginal oestrogens, and non-hormonal treatment for osteoporosis.3. We always propose psychological support to allow each woman to estimate and anticipate the consequences of PA.4. In case of uterine diseases such as fibroma, surgeons may propose a hysterectomy as well as PA, in which case oestrogens can be prescribed alone and progestins can be avoided (4).5. After PA, a gynaecological consultation is offered: HRT is given only to thoroughly informed women who really want it and have accepted PA with the assurance that they would have HRT afterwards. HRT is also offered to women who have had a prophylactic bilateral mastectomy. For other cases, clinical follow-up is proposed, and osteodensitometry is prescribed. If menopausal problems occur, alternative treatments are proposed first. For persistent problems, HRT is prescribed at the lowest dose for as long as the woman wishes. It is strongly recommended that treatment be stopped at the natural age of menopause, around 50 years of age.We think that over-alarmist information on menopause and strongly held beliefs against HRT lead some young women to refuse or delay an intervention that may save their life. Therefore, we advocate clear information, honest dialogue, and shared decision making with each woman.
MicroRNA Genes and Their Target 3′-Untranslated Regions Are Infrequently Somatically Mutated in Ovarian Cancers
Georgina L. Ryland, Jennifer L. Bearfoot, Maria A. Doyle, Samantha E. Boyle, David Y. H. Choong, Simone M. Rowley, Australian Ovarian Cancer Study Group , Richard W. Tothill, Kylie L. Gorringe, Ian G. Campbell
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0035805
Abstract: MicroRNAs are key regulators of gene expression and have been shown to have altered expression in a variety of cancer types, including epithelial ovarian cancer. MiRNA function is most often achieved through binding to the 3′-untranslated region of the target protein coding gene. Mutation screening using massively-parallel sequencing of 712 miRNA genes in 86 ovarian cancer cases identified only 5 mutated miRNA genes, each in a different case. One mutation was located in the mature miRNA, and three mutations were predicted to alter the secondary structure of the miRNA transcript. Screening of the 3′-untranslated region of 18 candidate cancer genes identified one mutation in each of AKT2, EGFR, ERRB2 and CTNNB1. The functional effect of these mutations is unclear, as expression data available for AKT2 and EGFR showed no increase in gene transcript. Mutations in miRNA genes and 3′-untranslated regions are thus uncommon in ovarian cancer.
Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
Collaborative Group on Epidemiological Studies of Ovarian Cancer
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001200
Abstract: Background Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05–1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m2 increase in body mass index was 1.10 (95% CI, 1.07–1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92–0.99; p = 0.02) in ever-users of hormone therapy. Conclusions Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade. Please see later in the article for the Editors' Summary
High Levels of Genomic Aberrations in Serous Ovarian Cancers Are Associated with Better Survival
Lars O. Baumbusch, ?slaug Helland, Yun Wang, Knut Liest?l, Marci E. Schaner, Ruth Holm, Dariush Etemadmoghadam, Kathryn Alsop, Pat Brown, Australian Ovarian Cancer Study Group , Gillian Mitchell, Sian Fereday, Anna DeFazio, David D. L. Bowtell, Gunnar B. Kristensen, Ole Christian Lingj?rde, Anne-Lise B?rresen-Dale
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054356
Abstract: Genomic instability and copy number alterations in cancer are generally associated with poor prognosis; however, recent studies have suggested that extreme levels of genomic aberrations may be beneficial for the survival outcome for patients with specific tumour types. We investigated the extent of genomic instability in predominantly high-grade serous ovarian cancers (SOC) using two independent datasets, generated in Norway (n = 74) and Australia (n = 70), respectively. Genomic instability was quantified by the Total Aberration Index (TAI), a measure of the abundance and genomic size of copy number changes in a tumour. In the Norwegian cohort, patients with TAI above the median revealed significantly prolonged overall survival (p<0.001) and progression-free survival (p<0.05). In the Australian cohort, patients with above median TAI showed prolonged overall survival (p<0.05) and moderately, but not significantly, prolonged progression-free survival. Results were confirmed by univariate and multivariate Cox regression analyses with TAI as a continuous variable. Our results provide further evidence supporting an association between high level of genomic instability and prolonged survival of high-grade SOC patients, possibly as disturbed genome integrity may lead to increased sensitivity to chemotherapeutic agents.
Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”
Sharon E. Johnatty equal contributor ,Jonathan Beesley equal contributor,Xiaoqing Chen,Stuart Macgregor,David L. Duffy,Amanda B. Spurdle,Anna deFazio,Natalie Gava,Penelope M. Webb,Australian Ovarian Cancer Study Group,Australian Cancer Study (Ovarian Cancer),Mary Anne Rossing,Jennifer Anne Doherty,Marc T. Goodman,Galina Lurie,Pamela J. Thompson,Lynne R. Wilkens,Roberta B. Ness,Kirsten B. Moysich,Jenny Chang-Claude,Shan Wang-Gohrke,Daniel W. Cramer,Kathryn L. Terry,Susan E. Hankinson,Shelley S. Tworoger,Montserrat Garcia-Closas,Hannah Yang,Jolanta Lissowska,Stephen J. Chanock,Paul D. Pharoah,Honglin Song,Alice S. Whitemore,Celeste L. Pearce,Daniel O. Stram,Anna H. Wu,Malcolm C. Pike,Simon A. Gayther,Susan J. Ramus,Usha Menon,Aleksandra Gentry-Maharaj,Hoda Anton-Culver,Argyrios Ziogas,Estrid Hogdall,Susanne K. Kjaer,Claus Hogdall,Andrew Berchuck,Joellen M. Schildkraut,Edwin S. Iversen,Patricia G. Moorman,Catherine M. Phelan,Thomas A. Sellers,Julie M. Cunningham,Robert A. Vierkant,David N. Rider,Ellen L. Goode,Izhak Haviv,Georgia Chenevix-Trench,Ovarian Cancer Association Consortium
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001016
Abstract: We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n = 675) and controls (n = 1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay. Based on Positive Predictive Value estimates, three SNPs—PODXL rs1013368, ITGA6 rs13027811, and MMP3 rs522616—were selected for replication using TaqMan genotyping in up to 3,059 serous invasive cases and 8,905 controls from 16 OCAC case-control studies. An additional 18 SNPs with Pper-allele<0.05 in the discovery stage were selected for replication in a subset of five OCAC studies (n = 1,233 serous invasive cases; n = 3,364 controls). The discovery stage associations in PODXL, ITGA6, and MMP3 were attenuated in the larger replication set (adj. Pper-allele≥0.5). However genotypes at TERT rs7726159 were associated with ovarian cancer risk in the smaller, five-study replication study (Pper-allele = 0.03). Combined analysis of the discovery and replication sets for this TERT SNP showed an increased risk of serous ovarian cancer among non-Hispanic whites [adj. ORper-allele 1.14 (1.04–1.24) p = 0.003]. Our study adds to the growing evidence that, like the 8q24 locus, the telomerase reverse transcriptase locus at 5p15.33, is a general cancer susceptibility locus.
Clinical trial update: International Breast Cancer Study Group
Karen N Price, Aron Goldhirsch, the International Breast Cancer Study Group
Breast Cancer Research , 2005, DOI: 10.1186/bcr1334
Abstract: The International Breast Cancer Study Group (IBCSG) opened its first generation of trials in 1978. The IBCSG includes both participating cooperative groups and individual institutions from all over the world. The groups are from Switzerland (Swiss Group for Clinical Cancer Research, 38 centers), Sweden (West Sweden Breast Cancer Study Group, 11 centers), Australia and New Zealand (Australian New Zealand Breast Cancer Trials Group, 56 centers), and Chile (GOCCHI, a Chilean cooperative group, 23 centers). Individual centers are located in Italy (14 centers), Slovenia, Hungary (2 centers), Spain, Romania, Austria, United Kingdom, Belgium (2 centers), Brazil, Peru, Hong Kong, India, South Africa (2 centers), and Canada.The IBCSG is conducting trials of tailored treatment approaches for these subpopulations: patients with endocrine non-responsive early breast cancer; older patients with endocrine non-responsive early breast cancer who are not candidates for standard chemotherapy regimens; and younger patients with endocrine responsive early breast cancer. Because each of these three populations is somewhat rare, treatment decisions tend to be based on the findings from the largest breast cancer population: middle-aged (median age 55) women with endocrine responsive breast cancer (i.e. estrogen receptor-positive and/or progesterone receptor-positive) who were included in trials of chemotherapy and of endocrine therapy across the board. Through subgroup analyses of these large heterogeneous trials we have identified distinct responsiveness features, and the current generation of IBCSG trials investigates treatments tailored to populations based on these features (Table 1). Examples of such trials are described below.The CM-Maintenance Trial (IBCSG 22-00) studies a tailored chemotherapy approach for patients with endocrine non-responsive tumors. The role of prolonged, low-dose chemotherapy after a standard adjuvant chemotherapy regimen to reduce the risk of relapse and impr
Functional Polymorphisms in the TERT Promoter Are Associated with Risk of Serous Epithelial Ovarian and Breast Cancers
Jonathan Beesley, Hilda A. Pickett, Sharon E. Johnatty, Alison M. Dunning, Xiaoqing Chen, Jun Li, Kyriaki Michailidou, Yi Lu, David N. Rider, Rachel T. Palmieri, Michael D. Stutz, Diether Lambrechts, Evelyn Despierre, Sandrina Lambrechts, Ignace Vergote, Jenny Chang-Claude, Stefan Nickels, Alina Vrieling, Dieter Flesch-Janys, Shan Wang-Gohrke, Ursula Eilber, Natalia Bogdanova, Natalia Antonenkova, Ingo B. Runnebaum, Thilo D?rk, Marc T. Goodman, Galina Lurie, Lynne R. Wilkens, Rayna K. Matsuno, Lambertus A. Kiemeney, Katja K. H. Aben, Tamara Marees, Leon F. A. G. Massuger, Brooke L. Fridley, Robert A. Vierkant, Elisa V. Bandera, Sara H. Olson, Irene Orlow, Lorna Rodriguez-Rodriguez, Linda S. Cook, Nhu D. Le, Angela Brooks-Wilson, Linda E. Kelemen, Ian Campbell, Simon A. Gayther, Susan J. Ramus, Aleksandra Gentry-Maharaj, Usha Menon, Shahana Ahmed, Caroline Baynes, Paul D. Pharoah, kConFab Investigators, Australian Ovarian Cancer Study Group , ABCTB Investigators , Kenneth Muir, Artitaya Lophatananon, Arkom Chaiwerawattana, Surapon Wiangnon, Stuart Macgregor, Douglas F. Easton, Roger R. Reddel, Ellen L. Goode, Georgia Chenevix-Trench, on behalf of the Ovarian Cancer Association Consortium
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024987
Abstract: Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.
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