18 results on '"Filipe C. Martins"'
Search Results
2. Supplementary Tables 1-6 from Evolutionary Pathways in BRCA1-Associated Breast Tumors
- Author
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Kornelia Polyak, Franziska Michor, Katharina Fetten, Judy E. Garber, Nadine Tung, Stuart J. Schnitt, Gabrielle Ethington, William Herlihy, Joanne L. Blum, So Yeon Park, Mithat Gönen, Vanessa Almendro, Subhajyoti De, and Filipe C. Martins
- Abstract
PDF file - 2.2MB
- Published
- 2023
3. Supplementary Figure 1 from Evolutionary Pathways in BRCA1-Associated Breast Tumors
- Author
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Kornelia Polyak, Franziska Michor, Katharina Fetten, Judy E. Garber, Nadine Tung, Stuart J. Schnitt, Gabrielle Ethington, William Herlihy, Joanne L. Blum, So Yeon Park, Mithat Gönen, Vanessa Almendro, Subhajyoti De, and Filipe C. Martins
- Abstract
PDF file - 171K, Optimization and validation of the techniques used.
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- 2023
4. Supplementary Figure 2 from Evolutionary Pathways in BRCA1-Associated Breast Tumors
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Kornelia Polyak, Franziska Michor, Katharina Fetten, Judy E. Garber, Nadine Tung, Stuart J. Schnitt, Gabrielle Ethington, William Herlihy, Joanne L. Blum, So Yeon Park, Mithat Gönen, Vanessa Almendro, Subhajyoti De, and Filipe C. Martins
- Abstract
PDF file - 149K, Evolutionary paths and BRCA1 expression in breast tumors.
- Published
- 2023
5. Data from Evolutionary Pathways in BRCA1-Associated Breast Tumors
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Kornelia Polyak, Franziska Michor, Katharina Fetten, Judy E. Garber, Nadine Tung, Stuart J. Schnitt, Gabrielle Ethington, William Herlihy, Joanne L. Blum, So Yeon Park, Mithat Gönen, Vanessa Almendro, Subhajyoti De, and Filipe C. Martins
- Abstract
BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.Significance: Defining the temporal order of tumor-driving somatic events is critical for early detection, risk stratification, and the design of chemopreventive therapies. Our combined experimental and computational approach reveal that the loss of wild-type BRCA1 may not be the first event in the majority of BRCA1-associated breast tumors and may not be present in all cancer cells within tumors. Cancer Discov; 2(6); 503–11. ©2012 AACR.This article is highlighted in the In This Issue feature, p. 473
- Published
- 2023
6. Somatic chromosomal number alterations affecting driver genes inform in-vitro and clinical drug response in high-grade serous ovarian cancer
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Thomas B.K. Watkins, James A. Hall, Charles Swanton, Carlos Caldas, Carolin M. Sauer, Barry R. Davies, Helen Bolton, Peter Baldwin, Sabina Cosulich, Maria Vias, Matthew D. Eldridge, Karen Hosking, Dominique-Laurent Couturier, James D. Brenton, Mercedes Jimenez-Linan, Robin Crawford, Krishnayan Haldar, Larissa S. Carnevalli, Ines de Santiago, Filipe C. Martins, Kevin Litchfield, Gabriel Funingana, Bristi Basu, Gerard I. Evan, John Latimer, Anna M. Piskorz, Iain A. McNeish, Anumithra Amirthanayagam, Deborah A. Sanders, Mihaela Angelova, Sohrab P. Shah, and Nicholas McGranahan
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Somatic cell ,business.industry ,Context (language use) ,mTORC1 ,Genome ,Clinical trial ,chemistry.chemical_compound ,Paclitaxel ,chemistry ,Cancer research ,Medicine ,business ,Gene ,PI3K/AKT/mTOR pathway - Abstract
The genomic complexity and heterogeneity of high-grade serous ovarian cancer (HGSOC) has hampered the realisation of successful therapies and effective personalised treatment is an unmet clinical need. Here we show that primary HGSOC spheroid models can be used to predict drug response and use them to demonstrate that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and drug response. These genes are often located in areas of the genome with frequent clonal SCNAs. MYC chromosomal copy number is associated with ex-vivo and clinical response to paclitaxel and ex-vivo response to mTORC1/2 inhibition. Activation of the mTOR survival pathway in the context to MYC-amplified HGSOC is mostly due to increased prevalence of SCNAs in genes from the PI3K pathway. These results suggest that SCNAs encompassing driver genes could be used to inform therapeutic response in the context of clinical trials testing personalised medicines.
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- 2020
7. Clinical and pathological associations of PTEN expression in ovarian cancer: a multicentre study from the Ovarian Tumour Tissue Analysis Consortium
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Scott H. Kaufmann, Daniel Guimarães Tiezzi, Valerie Rhenius, Gary L. Keeney, Alexander Hein, Dominique-Laurent Couturier, Florin Andrei Taran, Robert Edwards, Aline Talhouk, Stacey J. Winham, Christiani Bisinoto de Sousa, Nadja Pejovic, Andreas D. Hartkopf, Ramona Erber, Brenda Y. Hernandez, Jenny Lester, Teri A. Longacre, Anna L. Paterson, Peter Sinn, Robin Crawford, Lene Lundvall, Hugh Luk, Roberta B. Ness, Adekunle Odunsi, Suha Deen, Javier Benitez, Alice S. Whittemore, Anna Fischer, Anthony N. Karnezis, Christine Chow, Ana Osorio, Ellen L. Goode, Stefan Kommoss, Angela Brooks-Wilson, Linda E. Kelemen, Tanja Pejovic, Simon A. Gayther, Peter A. Fasching, Beth Y. Karlan, Jurandyr Moreira de Andrade, Samuel Leung, David D.L. Bowtell, James D. Brenton, Aleksandra Vrvilo, Marc T. Goodman, Paul D.P. Pharoah, Sara Y. Brucker, Honglin Song, Jennifer M Koziak, Robert A. Vierkant, Naveena Singh, Valerie McGuire, Chloe Karpinskyj, Mercedes Jimenez-Linan, Aleksandra Gentry-Maharaj, Anna deFazio, Jenny Chang-Claude, Linda S. Cook, Francesmary Modugno, Filipe C. Martins, Estrid Høgdall, Prafull Ghatage, Marie Lyne Alcaraz, Susan J. Ramus, Annette Staebler, Jennifer Alsop, David G. Huntsman, Joseph H. Rothstein, Tayyebeh M. Nazeran, Cristina Rodríguez-Antona, Luis Robles-Díaz, Bryan M. McCauley, María Jesús Gómez García, Michael E. Carney, Michael S. Anglesio, Yurii B. Shvetsov, Claus Høgdall, Sian Fereday, Martin Köbel, Maria P. Intermaggio, Sandra Orsulic, Luis Paz-Ares, Mary Anne Brett, Weiva Sieh, Matthias W. Beckmann, Helen Steed, Arndt Hartmann, Michael Schneider, Lynne R. Wilkens, Esther Herpel, Jacek Gronwald, Francisco José Candido dos Reis, Nhu D. Le, Gregg Nelson, Kirsten B. Moysich, Nadia Traficante, Usha Menon, Candido Dos Reis, Francisco J [0000-0001-5758-5917], Brenton, James D [0000-0002-5738-6683], Apollo - University of Cambridge Repository, Candido dos Reis, Francisco J. [0000-0001-5758-5917], and Brenton, James D. [0000-0002-5738-6683]
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Oncology ,Cancer Research ,692/4028/67/1517/1709 ,Carcinoma, Ovarian Epithelial ,Clear Cell ,Androgen ,ESTUDOS PROSPECTIVOS ,Cohort Studies ,Gene Knockout Techniques ,0302 clinical medicine ,Ovarian carcinoma ,Ovarian Epithelial ,Receptors ,Prospective Studies ,Progesterone ,Cancer ,Ovarian Neoplasms ,0303 health sciences ,Tumor ,Molecular medicine ,biology ,Hazard ratio ,article ,Age Factors ,Middle Aged ,Ovarian Cancer ,Serous fluid ,Receptors, Estrogen ,Receptors, Androgen ,030220 oncology & carcinogenesis ,Public Health and Health Services ,Biomarker (medicine) ,Female ,Receptors, Progesterone ,medicine.medical_specialty ,Oncology and Carcinogenesis ,Down-Regulation ,Adenocarcinoma ,03 medical and health sciences ,Rare Diseases ,Ovarian cancer ,Internal medicine ,Progesterone receptor ,medicine ,Biomarkers, Tumor ,PTEN ,Humans ,Oncology & Carcinogenesis ,030304 developmental biology ,Neoplasm Staging ,business.industry ,Tumor Suppressor Proteins ,Carcinoma ,PTEN Phosphohydrolase ,medicine.disease ,Estrogen ,692/4017 ,Androgen receptor ,Tissue Array Analysis ,biology.protein ,business ,Biomarkers ,Adenocarcinoma, Clear Cell - Abstract
Background PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. Methods Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran–Mantel–Haenszel tests. Results Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65–0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). Conclusions PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.
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- 2020
- Full Text
- View/download PDF
8. Combination of mTOR inhibition and paclitaxel as a personalised strategy in the context of MYC-amplified high-grade serous ovarian cancer
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James D. Brenton, Maria Vias, James A. Hall, D-L Couturier, Karen Hosking, Robin Crawford, Deborah A. Sanders, I. de Santiago, Filipe C. Martins, Mercedes Jimenez-Linan, and Anna M. Piskorz
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Hematology ,Precision medicine ,medicine.disease ,chemistry.chemical_compound ,Serous fluid ,Paclitaxel ,chemistry ,Internal medicine ,Ovarian carcinoma ,PARP inhibitor ,medicine ,Ovarian cancer ,business ,PI3K/AKT/mTOR pathway - Abstract
Background The extreme genomic heterogeneity of high-grade serous ovarian carcinoma (HGSOC) is a major barrier to precision medicine approaches. We have developed mutational signature analysis from shallow whole genome sequencing (sWGS) for molecular stratification and therapeutic prediction. PARP inhibitor therapy has significant survival advantage for women with germline BRCA1/2 mutations, but treatments and predictive biomarkers for women without homologous recombination deficiency have not been developed. MYC amplification is the most common driver in HGSOC, present in 42% of the TCGA cases. The best responder from the phase 1 trial of AZD2014 (dual m-TORC1/2 inhibitor) and paclitaxel in HGSOC had a mutation in MYC and we have hypothesised that biosynthetic effects of MYC are mediated through the mTOR pathway and blocked by AZD2014 perturbation. Methods Primary ovarian cancer spheroids were purified from 28 human ascites and profiled with sWGS. Ex-vivo therapeutic response was measured to four standard of care chemotherapeutic agents and eight inhibitors targeting nodal points of the PI3K and DNA damage repair pathways. RNA seq data from the TCGA HGSOC cohort was used to establish the genes whose expression was highly correlated with the expression of MYC. Results Ex-vivo assays were predictive of first-line clinical response to chemotherapy agents (P Conclusions Our results suggest that therapeutic strategies combining paclitaxel and inhibition of mTOR pathway can be used as personalised treatment in the context of MYC-amplified HGSOC. We are currently examining gene expression after AZD2014 pertubation in HGSOC models and performing the genomic analysis of cases from the phase 1 trial of AZD2014 and paclitaxel. Legal entity responsible for the study The authors. Funding Academy of Medical Sciences, Addenbrookes Charitable Trust, Cancer Research UK, University of Cambridge. Disclosure F.C. Martins: Research grant / Funding (self), The Clinical Lectureship from the Experimental Medicine Initiative is partly funded by AstraZeneca: AstraZeneca. All other authors have declared no conflicts of interest.
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- 2019
9. Gynecologic Oncology Training Systems in Europe
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Murat Gultekin, Polat Dursun, Boris Vranes, Rene Laky, Michaela Bossart, Jacek P. Grabowski, Jurgen M. J. Piek, Ranjit Manchanda, Christoph Grimm, Kastriot Dallaku, Syuzanna Babloyan, Anna Moisei, Toon Van Gorp, Isabelle Cadron, Peter Markov, Ana Micevska, Michael Halaska, Karina Dahl Steffensen, Liidia Gristsenko, Ritva Nissi, Eric Lambaudie, Zaza Tsitsishvili, Dimitrios Haidopoulos, Dimitrios Tsolakidis, Zoltan Novak, Michele Peiretti, Gauhar Dunenova, Ronalds Macuks, Thea E. Hetland, Trond M. Michelsen, Filipe C. Martins, Patriciu Achimas-Cadariu, Elena A. Ulrikh, Peter Uharcek, Sladjana Malic, Dejan Ognjenovic, Ignacio Zapardiel, Silke Johann, Vladyslav S. Sukhin, Obstetrics and gynaecology, CCA - Innovative therapy, MUMC+: MA Medische Staf Obstetrie Gynaecologie (9), Obstetrie & Gynaecologie, and RS: GROW - School for Oncology and Reproduction
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medicine.medical_specialty ,Standardization ,education ,Training system ,Training systems ,MEDLINE ,Harmonization ,Gynecologic oncology ,Medical Oncology ,ENYGO ,medicine ,Training ,Robotic surgery ,European Network of Young Gynaecological Oncologists ,Duration (project management) ,Gynecology ,Cancer prevention ,business.industry ,Obstetrics and Gynecology ,ESGO ,Europe ,Oncology ,Family medicine ,business - Abstract
Objective: The objectives of the study were to highlight some of the differences in training systems and opportunities for training in gynecologic oncology across Europe and to draw attention to steps that can be taken to improve training prospects and experiences of European trainees in gynecologic oncology. Methods: The European Network of Young Gynaecological Oncologists national representatives from 34 countries were asked to review and summarize the training system in their countries of origin and fulfill a mini-questionnaire evaluating different aspects of training. We report analysis of outcomes of the mini-questionnaire and subsequent discussion at the European Network of Young Gynaecological Oncologists national representatives Asian Pacific Organization for Cancer Prevention meeting in Istanbul (April 2010). Results: Training fellowships in gynecologic oncology are offered by 18 countries (53%). The median duration of training is 2.5 years (interquartile range, 2.0-3.0 years). Chemotherapy administration is part of training in 70.5% (24/34) countries. Most of the countries (26/34) do not have a dedicated national gynecologic-oncology journal. All trainees reported some or good access to training in advanced laparoscopic surgical techniques, whereas 41% indicated no access, and 59% some access to training opportunities in robotic surgery. European countries were grouped into 3 different categories on the basis of available training opportunities in gynecologic oncology: well-structured, moderately structured, and loosely structured training systems. Conclusions: There is a need for further harmonization and standardization of training programs and structures in gynecologic oncology across Europe. This is of particular relevance for loosely structured countries that lag behind the moderately structured and well-structured ones.
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- 2011
10. Increased Transglutaminase 2 and GLUT-1 Expression in Breast Tumors not Susceptible to Chemoprevention with Antioxidants
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Filipa Teixeira, Ines Reis, Margarida F. Dias, A. M. Silverio Cabrita, Nuno Geraldes, and Filipe C. Martins
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,040301 veterinary sciences ,Tissue transglutaminase ,9,10-Dimethyl-1,2-benzanthracene ,alpha-Tocopherol ,Normal tissue ,DMBA ,Breast Neoplasms ,Ascorbic Acid ,Antioxidants ,Gene Expression Regulation, Enzymologic ,0403 veterinary science ,Random Allocation ,03 medical and health sciences ,Breast cancer ,GTP-Binding Proteins ,Internal medicine ,Biomarkers, Tumor ,Animals ,Anticarcinogenic Agents ,Medicine ,Protein Glutamine gamma Glutamyltransferase 2 ,Treatment Failure ,Rats, Wistar ,Selenium Compounds ,Glucose Transporter Type 1 ,Transglutaminases ,biology ,business.industry ,04 agricultural and veterinary sciences ,General Medicine ,Ascorbic acid ,medicine.disease ,Micronutrient ,Immunohistochemistry ,Rats ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Endocrinology ,Oncology ,Carcinogens ,biology.protein ,Female ,business - Abstract
GoalsExpression of GLUT-1 and transglutaminase 2 is increased in aggressive breast cancer, whereas claudin-1, which is expressed in normal tissues, is absent in such tumors. This experimental study was undertaken to establish the aggressiveness and prognosis of DMBA-induced mammary tumors in female Wistar rats based on the assessment of these markers.Materials and methodsThe rats were divided into two groups, a control group (n = 70) and a chemoprevention group (n = 70). Breast tumors were induced in both groups by administration of 7,12-dimethylbenz[a]anthracene (DMBA). The chemoprevention group also received alpha-tocopherol and a solution of micronutrients containing ascorbic acid and selenium. Neoplastic lesions of both groups were randomly selected for immunohistochemical assessment of the expression of GLUT-1, transglutaminase 2 and claudin-1.ResultsA higher proportion of mammary tumors expressed GLUT-1 and transglutaminase 2 in the chemoprevention group. Claudin-1 expression was absent in all tumors of both groups.ConclusionsThese results are suggestive of increased aggressiveness of tumors not susceptible to chemoprevention by the agents used in this study.
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- 2009
11. Molecular profiling of human mammary gland links breast cancer risk to a p27+ cell population with progenitor characteristics
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Zhenhua Wu, S. Joyce Lin, Andrea L. Richardson, Rong Hu, Tatiana Nikolskaya, Judith Robens, Malcolm C. Pike, Laura Panos, Franziska Michor, Izhak Haviv, Adam Kowalczyk, Joanne L. Blum, Erik W. Thompson, Yu-Kang Cheng, Vanessa F. Merino, G. L. Chew, Saraswati Sukumar, Geoff Macintyre, Rulla M. Tamimi, E. Shelley Hwang, Gabrielle Ethington, Vilde Drageset Haakensen, Bryan Beresford-Smith, Yuri Nikolsky, Marina Bessarabova, Mary Jo Fackler, Reo Maruyama, Pedram Argani, Vanessa Almendro, Michael Grant, William Herlihy, Zoila A. Lopez-Bujanda, Antony Kaspi, Thomas C. Conway, Sibgat Choudhury, Filipe C. Martins, Jason Clark, Ying Su, Alfred Au, Kornelia Polyak, Stuart J. Schnitt, Judy Garber, April Greene-Colozzi, X. Shirley Liu, and Gedge D. Rosson
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Stromal cell ,endocrine system diseases ,Cellular differentiation ,Mammary gland ,Breast Neoplasms ,medicine.disease_cause ,Article ,Breast cancer ,Pregnancy ,medicine ,Genetics ,Humans ,Cell Lineage ,Progenitor cell ,skin and connective tissue diseases ,Mammary Glands, Human ,biology ,Gene Expression Profiling ,Stem Cells ,CD44 ,Cell Biology ,medicine.disease ,Parity ,medicine.anatomical_structure ,Immunology ,biology.protein ,Cancer research ,Molecular Medicine ,Female ,Stem cell ,Carcinogenesis ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
SummaryEarly full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44+p27+ cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27+ cells and their proliferation. Our results suggest that pathways controlling p27+ mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.
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- 2013
12. Evolutionary pathways in BRCA1-associated breast tumors
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Gabrielle Ethington, Katharina Fetten, Joanne L. Blum, Subhajyoti De, Nadine Tung, Vanessa Almendro, Filipe C. Martins, So Yeon Park, Franziska Michor, Judy Garber, Stuart J. Schnitt, Mithat Gonen, Kornelia Polyak, and William Herlihy
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Somatic cell ,Mutant ,Breast Neoplasms ,Bioinformatics ,medicine.disease_cause ,Cell Line, Tumor ,medicine ,Biomarkers, Tumor ,PTEN ,Humans ,skin and connective tissue diseases ,Mutation ,biology ,Cell growth ,BRCA1 Protein ,PTEN Phosphohydrolase ,Cancer ,medicine.disease ,Oncology ,Centrosome ,Cancer cell ,Cancer research ,biology.protein ,Female ,Tumor Suppressor Protein p53 - Abstract
BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population. Significance: Defining the temporal order of tumor-driving somatic events is critical for early detection, risk stratification, and the design of chemopreventive therapies. Our combined experimental and computational approach reveal that the loss of wild-type BRCA1 may not be the first event in the majority of BRCA1-associated breast tumors and may not be present in all cancer cells within tumors. Cancer Discov; 2(6); 503–11. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 473
- Published
- 2012
13. Microdialysis: improving local chemotherapy in cancer using a mathematical model
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Santos Jl, de Oliveira Cf, and Filipe C. Martins
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Drug ,Oncology ,medicine.medical_specialty ,Microdialysis ,Cancer chemotherapy ,media_common.quotation_subject ,medicine.medical_treatment ,Antineoplastic Agents ,Drug resistance ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Internal medicine ,Neoplasms ,Medicine ,Animals ,Humans ,media_common ,Chemotherapy ,General Immunology and Microbiology ,business.industry ,Drug Administration Routes ,Cancer ,Models, Theoretical ,medicine.disease ,Surgery ,Drug Resistance, Neoplasm ,Systemic administration ,business - Abstract
Although intratumoral chemotherapy administration has been evaluated in the past, its results have not been frequently comparable to those from systemic administration. We recently described microdialysis as a method for local chemotherapy administration with increasing effectiveness while reducing systemic toxicity. We present a mathematical model which supports the successful application of this procedure in optimizing the administered drug in different cases, using informatics tools and considering several parameters. We also review and discuss important aspects of cancer biology that should be taken into consideration in cancer chemotherapy, such as tumor heterogeneity, drug resistance and metastasis, and how this technique may be used to overcome any set-backs presented by these.
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- 2011
14. Cancer and deregulation of stem cells pathways
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Maria Filomena Botelho, António M. Cabrita, Maria Isabel Torgal, Filipe C. Martins, and Carlos Freire de Oliveira
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Mutation ,lcsh:Internal medicine ,Cancer Research ,Stem cells - Cancer - Wnt - Notch - Hedgehog ,Cellular differentiation ,Wnt signaling pathway ,Cancer ,lcsh:Other systems of medicine ,Biology ,medicine.disease_cause ,medicine.disease ,lcsh:RZ201-999 ,Cell biology ,Oncology ,Cancer stem cell ,medicine ,Cyclin-dependent kinase 8 ,Stem cell ,Carcinogenesis ,lcsh:RC31-1245 - Abstract
Stem cells may have an important etiological role in cancer. Their classic regulatory pathways are deregulated in tumors, strengthening the stem cell theory of cancer. In this manuscript, we review Wnt, Notch and Hedhehog pathways, describing which of their factors may be responsible for the neoplastic development. Furthermore, we classify these elements as oncogenes or tumor suppressor genes, demonstrating their mutation implications in cancer. The activation of these pathways is associated with the expression of certain genes which maintain proliferation and apoptosis inhibition. Further work should be carried out in the future in order to control tumor development by controlling these signaling cascades.
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- 2011
15. Chemoprevention and mammary neoplastic aggressiveness
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Filipa Teixeira, Nuno Geraldes, António Silvério Cabrita, Filipe C. Martins, Margarida F. Dias, and Ines Reis
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Pathology ,medicine.medical_specialty ,business.industry ,9,10-Dimethyl-1,2-benzanthracene ,alpha-Tocopherol ,Mammary Neoplasms, Experimental ,Ascorbic Acid ,Chemoprevention ,Rats ,Selenium ,Oncology ,Internal Medicine ,Medicine ,Animals ,Surgery ,Female ,Rats, Wistar ,business - Published
- 2008
16. Pregnancy and its role in breast cancer
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Mafalda Laranjo, Filipe C. Martins, António M. Cabrita, Maria Isabel Torgal, Carlos Freire de Oliveira, and Maria Filomena Botelho
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Oncology ,Cancer Research ,medicine.medical_specialty ,lcsh:Internal medicine ,medicine.drug_class ,Mammary gland ,Tumor inhibition ,medicine.disease_cause ,Pregnancy - Breast Cancer - Hormones - Mammary Gland - Carcinogenesis ,Breast cancer ,Internal medicine ,medicine ,lcsh:RC31-1245 ,Pregnancy ,business.industry ,lcsh:Other systems of medicine ,medicine.disease ,lcsh:RZ201-999 ,medicine.anatomical_structure ,Estrogen ,Cancer research ,Gravidez ,Stem cell ,business ,Carcinogenesis ,Neoplasias da Mama ,Hormone - Abstract
Early full-term pregnancy is the only recognized factor able to prevent breast cancer. There are several hypotheses to explain the mechanisms of this protection, namely an altered hormonal milieu, a differentiation process or a switch in stem cell properties. To explore them, authors have been using animal models, mainly in rodents. Hormonal administration with estrogen and progesterone was the most widely used process to mimic the mammary changes during pregnancy. We have recently proposed that this enigmatic protective role of a full-term birth in breast cancer is carried out by tumor inhibition mediated by differentiated mammary epithelial cells. This explanation may give a new perspective of breast cancer prevention and treatment.
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- 2008
17. Chemoprevention and Mammary Neoplastic Aggressiveness – Experimental Study
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Nuno Geraldes, Ines Reis, Filipa Teixeira, Margarida F. Dias, Filipe C. Martins, and António Silvério Cabrita
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Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2007
18. Cancer inhibition by normal differentiated cells
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Maria Filomena Botelho, Filipe C. Martins, C.F. de Oliveira, and António M. Cabrita
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Cancer Research ,Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,Cellular differentiation ,Medicine ,Cancer ,business ,medicine.disease - Published
- 2008
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