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Chemotherapy resistance ovarian carcinoma

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https://www.readbyqxmd.com/read/28197007/use-of-clozapine-alongside-chemotherapy-in-a-treatment-resistant-bipolar-disorder-patient-with-ovarian-carcinoma-a-case-report-and-brief-review
#1
Ashish Pakhre, Aarya Krishnan, Raman Deep Pattanayak, Sudhir K Khandelwal
Regular monitoring of blood counts ensures the safety of clozapine use; however, certain clinical situations may pose a dilemma for management such as use of clozapine in the presence of myelosuppressive chemotherapy. Further, there is very limited literature to guide such decisions. We report a case of a clozapine-stabilized, treatment-resistant bipolar disorder patient with ovarian carcinoma requiring chemotherapy. The clinical challenges are discussed in light of a brief review of the available reports.
October 2016: Indian Journal of Psychiatry
https://www.readbyqxmd.com/read/28187748/characterization-of-ovarian-clear-cell-carcinoma-using-target-drug-based-molecular-biomarkers-implications-for-personalized-cancer-therapy
#2
Mengjiao Li, Haoran Li, Fei Liu, Rui Bi, Xiaoyu Tu, Lihua Chen, Shuang Ye, Xi Cheng
BACKGROUND: It has long been appreciated that different subtypes (serous, clear cell, endometrioid and mucinous) of epithelial ovarian carcinoma (EOC) have distinct pathogenetic pathways. However, clinical management, especially chemotherapeutic regimens, for EOC patients is not subtype specific. Ovarian clear cell carcinoma (CCC) is a rare histological subtype of EOC, which exhibits high rates of recurrence and low chemosensitivity. We assessed potential therapeutic targets for ovarian CCC patients through analyzing the variation of drug-based molecular biomarkers expression between ovarian CCC and high-grade serous carcinoma (HGSC)...
February 10, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28185461/-epithelial-mesenchymal-transition-in-tumor-tissue-and-its-role-for-metastatic-spread-of-cancer
#3
V M Matějka, J Fínek, M Králíčková
BACKGROUND: Metastasis, recurrence, and resistance to chemotherapy are leading causes of the majority of cancer-related mortality worldwide. The process of metastasis can be artificially divided into a series of sequential, highly organized, and organ-specific steps. The underlying mechanisms are still poorly understood, but are believed to be mediated by epithelial-mesenchymal transition (EMT). First described in embryogenesis, EMT is a cellular reprogramming process in which epithelial cells acquire a mesenchymal phenotype...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28178720/erbb4-expression-in-ovarian-serous-carcinoma-resistant-to-platinum-based-therapy
#4
COMPARATIVE STUDY
Ozlen Saglam, Yin Xiong, Douglas C Marchion, Carolina Strosberg, Robert M Wenham, Joseph J Johnson, Daryoush Saeed-Vafa, Christopher Cubitt, Ardeshir Hakam, Anthony M Magliocco
Few data exist on the prognostic and predictive impact of erb-b2 receptor tyrosine kinase 4 (ERBB4) in ovarian cancer. Thus, we evaluated ERBB4 expression by immunohistochemistry in a tumor microarray consisting of 100 ovarian serous carcinoma specimens (50 complete responses [CRs] and 50 incomplete responses [IRs] to platinum-based therapy), 51 normal tissue controls, and 16 ovarian cancer cell lines. H scores were used to evaluate expression and were semiquantitatively classified into low, intermediate, and high categories...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
https://www.readbyqxmd.com/read/28161486/microrna-424-inhibits-cell-migration-invasion-and-epithelial-mesenchymal-transition-by-downregulating-doublecortin-like-kinase-1-in-ovarian-clear-cell-carcinoma
#5
Xin Wu, Yuanyuan Ruan, Hua Jiang, Congjian Xu
Doublecortin-like kinase 1 (DCLK1) is overexpressed in many cancers and acts as a tumor stem cell marker. Here, we investigated the role of DCLK1 and microRNA-424 (miR-424) in ovarian clear cell carcinoma (OCCC), a histopathologically distinct subtype of epithelial ovarian cancer associated with poor prognosis and chemotherapy resistance. Analysis of samples from 30 OCCC patients showed that DCLK1 was upregulated and miR-424 was downregulated in tumors compared with adjacent non-tumor tissues. DCLK1 overexpression promoted OCCC cell proliferation, migration, and invasion, whereas DCLK1 knockdown reduced cell viability and invasion and induced growth arrest in vitro and in vivo...
February 2, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28147318/keratin-5-overexpression-is-associated-with-serous-ovarian-cancer-recurrence-and-chemotherapy-resistance
#6
Carmela Ricciardelli, Noor A Lokman, Carmen E Pyragius, Miranda P Ween, Anne M Macpherson, Andrew Ruszkiewicz, Peter Hoffmann, Martin K Oehler
This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21)...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098079/hyperthermic-intraperitoneal-chemotherapy-for-peritoneal-surface-malignancies-a-single-institution-indian-experience
#7
S P Somashekhar, G Prasanna, Rajshekhar Jaka, Amit Rauthan, H S Murthy, Sunil Karanth
BACKGROUND: Cytoreductive surgery followed by hyper- thermic intraperitoneal chemotherapy (HIPEC) has shown better oncological outcomes in peritoneal surface malignancies (PSM). We assessed the feasibility and perioperative outcomes of this procedure in Indian patients. METHODS: In this prospective observational study from February 2013 to April 2015, we included 56 patients (41 females, 73.2%) with PSM. They had a good performance status, were either treatment-naïve or previously treated by surgery and systemic chemotherapy...
September 2016: National Medical Journal of India
https://www.readbyqxmd.com/read/28031529/the-prognostic-value-of-ki67-in-ovarian-high-grade-serous-carcinoma-an-11-year-cohort-study-of-chinese-patients
#8
Ming Chen, Shuzhong Yao, Qinghua Cao, Meng Xia, Junxiu Liu, Mian He
OBJECTIVE: This study sought to assess the prognostic role of Ki67 in primary ovarian high-grade serous carcinoma (HGSC) and to determine whether Ki67 expression can predict responsiveness to platinum and paclitaxel chemotherapy. RESULTS: A total of 318 women were included in the analysis and the median follow-up time was 48 months (range, 3-150 months). Ki67 proliferation indices ranged from 3% to 95% with a median of 40%. Using 40% as the cut-off value for the Ki67 index, we classified 141 patients as having low Ki67 expression and 177 patients as having high Ki67 expression...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27941884/emergent-role-of-the-fractalkine-axis-in-dissemination-of-peritoneal-metastasis-from-epithelial-ovarian-carcinoma
#9
H Gurler Main, J Xie, G G Muralidhar, O Elfituri, H Xu, A A Kajdacsy-Balla, M V Barbolina
Epithelial ovarian carcinoma is the most common cause of death from gynecologic cancers largely due to advanced, relapsed and chemotherapy-resistant peritoneal metastasis, which is refractory to the currently used treatment approaches. Mechanisms supporting advanced and relapsed peritoneal metastasis are largely unknown, precluding development of more effective targeted therapies. In this study, we investigated the function of a potentially targetable fractalkine axis in the formation and the development of advanced and relapsed peritoneal metastasis and its impact on patients' outcomes...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27941566/folate-receptor-alpha-expression-in-platinum-resistant-refractory-ovarian-carcinomas-and-primary-endocervical-adenocarcinomas
#10
Lisa A Rubinsak, Cynthia Cohen, Namita Khanna, Ira R Horowitz, Krisztina Z Hanley
INTRODUCTION: Treatment of advanced stage ovarian carcinoma is challenging, and despite surgical treatment and chemotherapy, the 5-year survival rate is estimated around 30%. Early recurrence and resistance to platinum-based chemotherapy are associated with poor prognosis and limited response to available second-line chemotherapy. The relative incidence of endocervical adenocarcinoma (EAC) compared with squamous cell carcinoma is increasing. Although the first-line treatment modality for early stage EAC is surgical resection, for locally advanced disease chemoradiation or neoadjuvant chemotherapy is used...
December 9, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27937085/an-in-vitro-demonstration-of-overcoming-drug-resistance-in-skov3-tr-and-mcf7-adr-with-targeted-delivery-of-polymer-pro-drug-conjugates
#11
Prashant Bhattarai, Dylan Vance, Arash Hatefi, Ban An Khaw
Drug resistance is a common phenomenon that occurs in cancer chemotherapy. Delivery of chemotherapeutic agents as polymer pro-drug conjugates (PPDCs) pretargeted with bispecific antibodies could circumvent drug resistance in cancer cells. To demonstrate this approach to overcome drug resistance, Paclitaxel (Ptxl) resistant SKOV3 TR human ovarian- and doxorubicin (Dox) resistant MCF7 ADR human mammary-carcinoma cell lines were used. Pre-targeting over-expressed biotin or HER2/neu receptors on cancer cells was conducted by biotinylated anti-DTPA or Anti-HER2/neu affibody - anti-DTPA Fab bispecific antibody complexes...
December 12, 2016: Journal of Drug Targeting
https://www.readbyqxmd.com/read/27918136/development-of-cell-permeable-non-helical-constrained-peptides-to-target-a-key-protein-protein-interaction-in-ovarian-cancer
#12
Mareike M Wiedmann, Yaw Sing Tan, Yuteng Wu, Shintaro Aibara, Wenshu Xu, Hannah F Sore, Chandra S Verma, Laura Itzhaki, Murray Stewart, James D Brenton, David R Spring
There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines. To inhibit the protein function, cell-permeable, non-helical constrained proteomimetics to target the HNF1β-importin α protein-protein interaction were designed, guided by X-ray crystallographic data and molecular dynamics simulations...
January 9, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27917296/stat1-associated-intratumoural-th1-immunity-predicts-chemotherapy-resistance-in-high-grade-serous-ovarian-cancer
#13
Katrina K Au, Cécile Le Page, Runhan Ren, Liliane Meunier, Isabelle Clément, Kathrin Tyrishkin, Nichole Peterson, Jennifer Kendall-Dupont, Timothy Childs, Julie-Ann Francis, Charles H Graham, Andrew W Craig, Jeremy A Squire, Anne-Marie Mes-Masson, Madhuri Koti
High-grade serous ovarian carcinoma (HGSC) accounts for 70% of all epithelial ovarian cancers but clinical management is challenged by a lack of accurate prognostic and predictive biomarkers of chemotherapy response. This study evaluated the role of Signal Transducer and Activator of Transcription 1 (STAT1) as an independent prognostic and predictive biomarker and its correlation with intratumoural CD8(+) T cells in a second independent biomarker validation study. Tumour STAT1 expression and intratumoural CD8(+) T cell infiltration were assessed by immunohistochemistry as a multicentre validation study conducted on 734 chemotherapy-naïve HGSCs...
October 2016: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#14
Noriomi Matsumura, Ken Yamaguchi, Ryusuke Murakami, Masaki Mandai, Ikuo Konishi
Genome-wide analyses have recently been reported for ovarian cancer. High-grade serous ovarian carcinoma(HGSOC) almost exclusively harbor TP53 mutations and prominent copy number aberrations. Approximately 20% of HGSOCs harbor BRCA mutations, in which case PARP inhibitors may be effective. HGSOCs are classified into 4 molecular subtypes with distinct histopathological features by transcriptional profiling. These subtypes differ in prognosis and drug sensitivity. Additionally, a whole-genome analysis for HGSOC has revealed various factors that can induce resistance to chemotherapy...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/27825116/ginsenoside-rb1-targets-chemotherapy-resistant-ovarian-cancer-stem-cells-via-simultaneous-inhibition-of-wnt-%C3%AE-catenin-signaling-and-epithelial-to-mesenchymal-transition
#15
Shan Deng, Chris Kong Chu Wong, Hung-Cheng Lai, Alice Sze Tsai Wong
Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767100/ccne1-copy-number-gain-and-overexpression-identify-ovarian-clear-cell-carcinoma-with-a-poor-prognosis
#16
Ayse Ayhan, Elisabetta Kuhn, Ren-Chin Wu, Hiroshi Ogawa, Asli Bahadirli-Talbott, Tsui-Lien Mao, Haruhiko Sugimura, Ie-Ming Shih, Tian-Li Wang
Ovarian clear cell carcinoma is a unique type of ovarian cancer, often derived from endometriosis, and advanced-stage disease has a dismal prognosis primarily due to the resistance to conventional chemotherapy. Previous studies have shown frequent somatic mutations in ARID1A, PIK3CA, hTERT promoter, and amplification of ZNF217; however, the molecular alterations that are associated with its aggressiveness remain largely unknown. This study examined and compared cyclin E1 expression in endometriosis-related ovarian tumors, with the aim of determining the relationship between hTERT mutations and ARID1A expression and evaluating the effects of these molecular alterations on patient survival...
February 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27711690/near-infrared-light-mediated-photoactivation-of-cytotoxic-re-i-complexes-by-using-lanthanide-doped-upconversion-nanoparticles
#17
Ming Hu, Jixian Zhao, Xiangzhao Ai, Maja Budanovic, Jing Mu, Richard D Webster, Qian Cao, Zongwan Mao, Bengang Xing
Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation...
September 13, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27671528/novel-abcg2-antagonists-reverse-topotecan-mediated-chemotherapeutic-resistance-in-ovarian-carcinoma-xenografts
#18
Jerec W Ricci, Debbie M Lovato, Virginia Severns, Larry A Sklar, Richard S Larson
Chemotherapeutic resistance remains a challenge in the treatment of ovarian carcinoma, especially in recurrent disease. Despite the fact that most patients with newly diagnosed tumors attain complete remission following cytoreductive surgery and chemotherapy, ovarian carcinoma has a recurrence rate that exceeds 75%. The ATP-binding cassette family G member 2 (ABCG2) efflux protein has been described as one mechanism that confers multiple-drug resistance to solid tumors and contributes to topotecan resistance in ovarian carcinoma...
December 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27663731/improved-i-p-drug-delivery-with-bioadhesive-nanoparticles
#19
Yang Deng, Fan Yang, Emiliano Cocco, Eric Song, Junwei Zhang, Jiajia Cui, Muneeb Mohideen, Stefania Bellone, Alessandro D Santin, W Mark Saltzman
The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27641463/-high-dose-chemotherapy-as-a-strategy-to-overcome-drug-resistance-in-solid-tumors
#20
REVIEW
Frédéric Selle, Joseph Gligorov, Daniele G Soares, Jean-Pierre Lotz
The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated...
October 2016: Bulletin du Cancer
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