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Ovarian cancer treatment personalized

Daniel Altman, Rebecca G Rogers, Li Yin, Karl Tamussino, Weimin Ye, Cheryl B Iglesia
OBJECTIVE: To assess whether there is any association between the implantation of synthetic polypropylene mesh slings for the treatment of stress urinary incontinence (SUI) and risk of cancer. METHODS: We performed a nationwide cohort study based on the general female population in Sweden. All women entered the observational period as unexposed on January 1, 1997, and contributed person-time as unexposed unless they underwent a midurethral sling procedure for SUI, after which they contributed person-time as exposed until first occurrence of any cancer, death, emigration, or end of the observational period (December 31, 2009)...
March 2018: Obstetrics and Gynecology
Sarah Braungart, Ross J Craigie, Paul D Losty
BACKGROUND: No clear treatment and follow-up protocols have been established for prepubertal patients with ovarian tumours. The lack of adequate prospective data in the literature includes all aspects of their management. A significant number of children with ovarian masses present out of hours as a surgical emergency and are initially managed by paediatric surgeons without special interest in surgical oncology. Clear guidance on the management of such tumours is therefore fundamental...
December 27, 2017: Journal of Pediatric Surgery
Malgorzata Milewska, Mattia Cremona, Clare Morgan, John O'Shea, Aoife Carr, Sri H Velanki, Ann M Hopkins, Sinead Toomey, Stephen F Madden, Bryan T Hennessy, Alex J Eustace
Background: The application of genomic technologies to patient tumor samples identified groups of signaling pathways which acquire activating mutations. Some cancers are dependent on these mutations and the aberrant proteins resulting from these mutations can be targeted by novel drugs which can eradicate the cancer. Methods: We used to determine the frequency of ERBB mutations in solid tumors. We then determined the sensitivity of a panel of cell lines to clinically available PI3K inhibitors...
2018: Therapeutic Advances in Medical Oncology
Bo Gao, Yi Lu, Annemieke J M Nieuweboer, Hongmei Xu, Jonathan Beesley, Ingrid Boere, Anne-Joy M de Graan, Peter de Bruijn, Howard Gurney, Catherine J Kennedy, Yoke-Eng Chiew, Sharon E Johnatty, Philip Beale, Michelle Harrison, Craig Luccarini, Don Conroy, Ron H J Mathijssen, Paul R Harnett, Rosemary L Balleine, Georgia Chenevix-Trench, Stuart Macgregor, Anna de Fazio
Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given cyclically multiple blood sampling is required to adequately define drug disposition, limiting patient recruitment. We found that carboplatin and paclitaxel disposition are stable phenotypes in ovarian cancer patients and tested a genome-wide association study (GWAS) design to identify SNPs associated with chemotherapy disposition...
January 24, 2018: Scientific Reports
Wei Wei, Zequn Sun, Willian A da Silveira, Zhenning Yu, Andrew Lawson, Gary Hardiman, Linda E Kelemen, Dongjun Chung
Identification of cancer patient subgroups using high throughput genomic data is of critical importance to clinicians and scientists because it can offer opportunities for more personalized treatment and overlapping treatments of cancers. In spite of tremendous efforts, this problem still remains challenging because of low reproducibility and instability of identified cancer subgroups and molecular features. In order to address this challenge, we developed Integrative Genomics Robust iDentification of cancer subgroups (InGRiD), a statistical approach that integrates information from biological pathway databases with high-throughput genomic data to improve the robustness for identification and interpretation of molecularly-defined subgroups of cancer patients...
January 1, 2018: Statistical Methods in Medical Research
Fei Chen, Nicholas J Roberts, Alison P Klein
Pancreatic cancers arise through a series of genetic events both inherited and acquired. Inherited genetic changes, both high penetrance and low penetrance, are an important component of pancreatic cancer risk, and may be used to characterize populations who will benefit from early detection. Furthermore, pancreatic cancer patients with inherited mutations may be particularly sensitive to certain targeted agents, providing an opportunity to personalized treatment. Family history of pancreatic cancer is one of the strongest risk factors for the disease, and is associated with an increased risk of caners at other sites, including but not limited to breast, ovarian and colorectal cancer...
December 2017: Chinese Clinical Oncology
Howard W Bruckner, Daniel Gurell, Azriel Hirschfeld
BACKGROUND/AIM: Bevacizumab (bev), when added to a moderate dose combination of previously failed cytotoxins, as a third- and fourth-line therapy for refractory gastric, cholangiocarcinoma, and ovarian cancers, produced high-quality responses. The regimen was based on preclinical models designed in order to simultaneously partner both bev and each of the cytotoxins with 4-5 synergistic drugs. PATIENTS AND METHODS: Eligible patients (n=9) had high-grade endometrial tumors and had failed standard chemotherapy...
January 2018: Anticancer Research
Hong Kyu Jung, Suyeon Park, Nam Won Kim, Jong Eun Lee, Zisun Kim, Sun Wook Han, Sung Mo Hur, Sung Young Kim, Cheol Wan Lim, Min Hyuk Lee, Jihyoun Lee
Purpose: Breast cancer survivors have slightly increased the risk of second primary cancers. Breast, colon, uterine, and ovarian cancers are common secondary cancers in breast cancer survivors. In this study, we assessed the development of second primary cancers of breast cancer survivors in Korea. Methods: Medical records of patients with breast cancer in 3 tertiary medical institutions were reviewed retrospectively. We evaluated secondary malignancy diagnosed at least 2 months after the breast cancer diagnosis...
December 2017: Annals of Surgical Treatment and Research
Alexander J Cortez, Patrycja Tudrej, Katarzyna A Kujawa, Katarzyna M Lisowska
Epithelial ovarian cancer is typically diagnosed at an advanced stage. Current state-of-the-art surgery and chemotherapy result in the high incidence of complete remissions; however, the recurrence rate is also high. For most patients, the disease eventually becomes a continuum of symptom-free periods and recurrence episodes. Different targeted treatment approaches and biological drugs, currently under development, bring the promise of turning ovarian cancer into a manageable chronic disease. In this review, we discuss the current standard in the therapy for ovarian cancer, major recent studies on the new variants of conventional therapies, and new therapeutic approaches, recently approved and/or in clinical trials...
December 16, 2017: Cancer Chemotherapy and Pharmacology
B J Monk, J K Chan
The role of intraperitoneal (i.p.) chemotherapy in treating newly diagnosed advanced epithelial ovarian cancer (EOC) has been the subject of controversy for almost three decades. Three large intergroup phase III trials (GOG 104, 114, 172) have demonstrated a survival benefit associated with i.p. over intravenous (i.v.) therapy in advanced, low-volume EOC. Despite the positive clinical trial results and a subsequent National Cancer Institute alert in 2006, i.p. treatment has not been widely accepted as the standard of care in the United States and is infrequently used in Europe...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
W Wei, F Giulia, S Luffer, R Kumar, B Wu, M Tavallai, R T Bekele, M J Birrer
Background: Despite improvements in diagnostics and treatment, the clinical outcome of epithelial ovarian cancer remains poor over the last three decades. Recent high-throughput genomic studies have demonstrated ovarian cancer as a highly heterogeneous entity with distinctive molecular signatures among different or even within the same histotype. In this article, we review the molecular genetics of epithelial ovarian cancer and how they have been translated into modern clinical trials, as well as their implications in patient stratification for more targeted and personalized approaches...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
S Pignata, S C Cecere, A Du Bois, P Harter, F Heitz
Despite optimal surgery and appropriate first-line chemotherapy, ∼70%-80% of patients with epithelial ovarian cancer will develop disease relapse. The same modalities as used primarily are available for treatment of recurrent ovarian cancer (ROC). The rationale for repetitive surgery in ROC was based on a stable body of retrospective data; however, prospective data were missing. Now, preliminary data from the prospective AGO-DESKTOP III give evidence that surgery for ROC seems to be of benefit for selected patients with platinum-sensitive relapse undergoing complete resection...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Fang Fang, Horacio Cardenas, Hao Huang, Guanglong Jiang, Susan M Perkins, Chi Zhang, Harold N Keer, Yunlong Liu, Kenneth P Nephew, Daniela Matei
DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer. In this study, we elucidated an epigenetic signature associated with platinum drug resensitization that may offer utility in predicting the outcomes of patients who are coadministered a DNA methyltransferase inhibitor. The ovarian cancer specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant ovarian cancer who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard-of-care chemotherapy regimen selected by the treating physician...
February 1, 2018: Cancer Research
Dawid T Janczak, Malgorzata K Mimier, Robert D McBane, Patrick S Kamath, Benjamin S Simmons, Dalene M Bott-Kitslaar, Charles J Lenz, Emily R Vargas, David O Hodge, Waldemar E Wysokinski
OBJECTIVES: To assess the outcome of direct oral anticoagulants (DOACs), specifically Xa inhibitors: rivaroxaban and apixaban, for the treatment of venous thromboembolism (VTE) of atypical location (VTE-AL), portal, mesenteric, hepatic, splenic, gonadal, renal, and cerebral veins, prospectively collected data of Mayo Thrombophilia Clinic Registry were used. METHODS: Patients with acute VTE-AL treated with DOACs, enrolled between March 1, 2013, and February 1, 2017, were compared with patients with VTE of typical location (VTE-TL: deep vein thrombosis of extremities and/or pulmonary embolism) receiving DOACs and with patients with VTE-AL treated with enoxaparin...
January 2018: Mayo Clinic Proceedings
Mariana Castells
Drug allergy is a rising problem in the twenty-first century which affects all populations and races, children, and adults, and for which the recognition, diagnosis, management, and treatment is still not well standardized. Classical and new chemotherapy drugs, monoclonal antibodies (MoAbs), and small molecules to treat cancer and chronic inflammatory diseases are aimed at improving quality of life and life expectancy of patients, but an increasing number of reactions including anaphylaxis precludes their use in targeted populations...
2017: Frontiers in Immunology
Susan K Lutgendorf, Premal H Thaker, Jesusa M Arevalo, Michael J Goodheart, George M Slavich, Anil K Sood, Steve W Cole
BACKGROUND: Social factors in the patient macroenvironment have been shown to influence molecular events in the tumor microenvironment and thereby influence cancer progression. However, biomarkers providing a window into the longitudinal effects of biobehavioral factors on tumor biology over time are lacking. Exosome analysis is a novel strategy for in vivo monitoring of dynamic changes in tumor cells. This study examined exosomal profiles from patients with low or high levels of social support for epithelial-mesenchymal transition (EMT) polarization and gene expression related to inflammation and β-adrenergic signaling...
November 7, 2017: Cancer
Naoki Kawahara, Kenji Ogawa, Mika Nagayasu, Mai Kimura, Yoshikazu Sasaki, Hiroshi Kobayashi
Inhibitors of poly(ADP-ribose) polymerase (PARP) are new types of personalized treatment of relapsed platinum-sensitive ovarian cancer harboring BRCA1/2 mutations. Ovarian clear cell cancer (CCC), a subset of ovarian cancer, often appears as low-stage disease with a higher incidence among Japanese. Advanced CCC is highly aggressive with poor patient outcome. The aim of the present study was to determine the potential synthetic lethality gene pairs for PARP inhibitions in patients with CCC through virtual and biological screenings as well as clinical studies...
November 2017: Biomedical Reports
Eden R Padayachee, Fleury Augustin Nsole Biteghe, Zaria Malindi, Dirk Bauerschlag, Stefan Barth
Considerable research efforts have been dedicated to understanding ovarian and breast cancer mechanisms, but there has been little progress translating the research into effective clinical applications. Hence, personalized/precision medicine has emerged because of its potential to improve the accuracy of tumor targeting and minimize toxicity to normal tissue. Targeted therapy in both breast and ovarian cancer has focused on antibodies, antibody drug conjugates (ADCs), and very recently the introduction of human antibody fusion proteins...
September 2017: Transfusion Medicine and Hemotherapy
Kyung Jin Eoh, Young Shin Chung, So Hyun Lee, Sun-Ae Park, Hee Jung Kim, Wookyeom Yang, In Ok Lee, Jung-Yun Lee, Hanbyoul Cho, Doo Byung Chay, Sunghoon Kim, Sang Wun Kim, Jae-Hoon Kim, Young Tae Kim, Eun Ji Nam
Purpose: Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients. Materials and Methods: Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included...
October 17, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
Ellen L Goode, Matthew S Block, Kimberly R Kalli, Robert A Vierkant, Wenqian Chen, Zachary C Fogarty, Aleksandra Gentry-Maharaj, Aleksandra Toloczko, Alexander Hein, Aliecia L Bouligny, Allan Jensen, Ana Osorio, Andreas D Hartkopf, Andy Ryan, Anita Chudecka-Glaz, Anthony M Magliocco, Arndt Hartmann, Audrey Y Jung, Bo Gao, Brenda Y Hernandez, Brooke L Fridley, Bryan M McCauley, Catherine J Kennedy, Chen Wang, Chloe Karpinskyj, Christiani B de Sousa, Daniel G Tiezzi, David L Wachter, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gregg Nelson, Jan Lubinski, Janusz Menkiszak, Jennifer Alsop, Jenny Lester, Jesús García-Donas, Jill Nation, Jillian Hung, José Palacios, Joseph H Rothstein, Joseph L Kelley, Jurandyr M de Andrade, Luis Robles-Díaz, Maria P Intermaggio, Martin Widschwendter, Matthias W Beckmann, Matthias Ruebner, Mercedes Jimenez-Linan, Naveena Singh, Oleg Oszurek, Paul R Harnett, Peter F Rambau, Peter Sinn, Philipp Wagner, Prafull Ghatage, Raghwa Sharma, Robert P Edwards, Roberta B Ness, Sandra Orsulic, Sara Y Brucker, Sharon E Johnatty, Teri A Longacre, Ursula Eilber, Valerie McGuire, Weiva Sieh, Yanina Natanzon, Zheng Li, Alice S Whittemore, Anna deFazio, Annette Staebler, Beth Y Karlan, Blake Gilks, David D Bowtell, Estrid Høgdall, Francisco J Candido Dos Reis, Helen Steed, Ian G Campbell, Jacek Gronwald, Javier Benítez, Jennifer M Koziak, Jenny Chang-Claude, Kirsten B Moysich, Linda E Kelemen, Linda S Cook, Marc T Goodman, María José García, Peter A Fasching, Stefan Kommoss, Suha Deen, Susanne K Kjaer, Usha Menon, James D Brenton, Paul D P Pharoah, Georgia Chenevix-Trench, David G Huntsman, Stacey J Winham, Martin Köbel, Susan J Ramus
Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium...
October 12, 2017: JAMA Oncology
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