Read by QxMD icon Read

Carboplatin resistant ovarian cancer

Jose F Ponte, Olga Ab, Leanne Lanieri, Jenny Lee, Jennifer Coccia, Laura M Bartle, Marian Themeles, Yinghui Zhou, Jan Pinkas, Rodrigo Ruiz-Soto
Elevated folate receptor alpha (FRα) expression is characteristic of epithelial ovarian cancer (EOC), thus establishing this receptor as a candidate target for the development of novel therapeutics to treat this disease. Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that targets FRα for tumor-directed delivery of the maytansinoid DM4, a potent agent that induces mitotic arrest by suppressing microtubule dynamics. Here, combinations of IMGN853 with approved therapeutics were evaluated in preclinical models of EOC...
November 24, 2016: Neoplasia: An International Journal for Oncology Research
S Pontikakis, C Papadaki, M Tzardi, M Trypaki, M Sfakianaki, F Koinis, E Lagoudaki, L Giannikaki, A Kalykaki, E Kontopodis, Z Saridaki, N Malamos, V Georgoulias, J Souglakos
To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR...
October 25, 2016: Pharmacogenomics Journal
Nicoletta Staropoli, Domenico Ciliberto, Silvia Chiellino, Francesca Caglioti, Teresa Del Giudice, Simona Gualtieri, Angela Salvino, Alessandra Strangio, Cirino Botta, Sandro Pignata, Pierfrancesco Tassone, Pierosandro Tagliaferri
OBJECTIVES: The current gold-standard for the first-line treatment in IIIb/IV stages of epithelial ovarian cancer (EOC) is the combination of carboplatin and paclitaxel plus bevacizumab in some countries. In the era of personalized medicine, there is still uncertainty on the impact of several molecularly targeted agents, which have been investigated for the management of this disease. To shed light on the actual role of targeted therapy in EOC, a systematic review and meta-analysis was performed...
October 13, 2016: Oncotarget
Christopher Poon, Xiaopin Duan, Christina Chan, Wenbo Han, Wenbin Lin
Due to the ability of ovarian cancer (OCa) to acquire drug resistance, it has been difficult to develop efficient and safe chemotherapy for OCa. Here, we examined the therapeutic use of a new self-assembled core-shell nanoscale coordination polymer nanoparticle (NCP-Carbo/GMP) that delivers high loadings of carboplatin (28.0±2.6 wt.%) and gemcitabine monophosphate (8.6±1.5 wt.%). A strong synergistic effect was observed between carboplatin and gemcitabine against platinum-resistant OCa cells, SKOV-3, and A2780/CDDP in vitro...
October 6, 2016: Molecular Pharmaceutics
Sham S Kakar, Christopher A Worth, Zhenglong Wang, Kelsey Carter, Mariusz Ratajczak, Pranesh Gunjal
Ovarian cancer is a highly aggressive and deadly disease. Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly cisplatin or carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately, after few months of initial treatment, tumor relapse occurs due to platinum-resistance. DOXIL (liposomal preparation of doxorubicin) is a choice of drug for recurrent ovarian cancer. However, its response rate is very low and is accompanied by myocardial toxicity...
2016: Journal of Cancer Stem Cell Research
Leslie A Garrett, Whitfield B Growdon, Bo R Rueda, Rosemary Foster
BACKGROUND: Pre-clinical studies have demonstrated that natural and synthetic histone deacetylase (HDAC) inhibitors can impede the in vitro and in vivo growth of cell lines from a variety of gynecologic and other malignancies. We investigated the anti-tumor activity of panobinostat (LBH589) both in vitro and in vivo as either a single agent or in combination with conventional cytotoxic chemotherapy using patient-derived xenograft (PDX) models of primary serous ovarian tumors. METHODS: The ovarian cancer cell lines OVCAR8, SKOV3 and their paclitaxel-resistant derivatives OVCAR8-TR and SKOV3-TR were treated with increasing doses of LBH589...
2016: Journal of Ovarian Research
Mariam M AlHilli, Marc A Becker, S John Weroha, Karen S Flatten, Rachel M Hurley, Maria I Harrell, Ann L Oberg, Matt J Maurer, Kieran M Hawthorne, Xiaonan Hou, Sean C Harrington, Sarah McKinstry, X Wei Meng, Keith M Wilcoxen, Kimberly R Kalli, Elizabeth M Swisher, Scott H Kaufmann, Paul Haluska
OBJECTIVE: Poly(ADP-ribose) polymerase (PARP) inhibitors have yielded encouraging responses in high-grade serous ovarian carcinomas (HGSOCs), but the optimal treatment setting remains unknown. We assessed the effect of niraparib on HGSOC patient-derived xenograft (PDX) models as well as the relationship between certain markers of homologous recombination (HR) status, including BRCA1/2 mutations and formation of RAD51 foci after DNA damage, and response of these PDXs to niraparib in vivo...
September 7, 2016: Gynecologic Oncology
Lu Yang, Shadi Moghaddas, Homa Dezvareh, Louiza Belkacemi, Steven J Bark, Rathindra N Bose, Loi H Do
Phosphaplatins are platinum-based antitumor compounds that, unlike other clinically utilized platinum drugs (i.e. cisplatin, carboplatin, and oxaliplatin), appear to target proteins rather than DNA. Because of their unique mode of action, phosphaplatins are promising drug candidates for cisplatin-resistant cancers. In this study, we discovered that Pt(II) and Pt(IV) phosphaplatins possess diverse antitumor properties. In addition to targeting apoptosis antigen (FAS) and proapoptotic gene products as described previously, phosphaplatins also target angiogenesis...
July 27, 2016: Journal of Inorganic Biochemistry
Jin-Gyoung Jung, Ie-Ming Shih, Joon Tae Park, Emily Gerry, Tae Hoen Kim, Ayse Ayhan, Karen Handschuh, Ben Davidson, Amanda Nickles Fader, Licia Selleri, Tian-Li Wang
The evolution of chemoresistance is a fundamental characteristic of cancer that ultimately defeats its clinical management. However, it may be possible improve patient outcomes significantly by defeating nodal resistance mechanisms which cancers rely upon during the evolution to an untreatable state. Here we report an essential role for upregulation of the stem cell reprogramming factor PBX1 in mediating chemoresistance in recurrent ovarian carcinomas. In clinical specimens, high levels of PBX1 expression correlated with shorter survival in post-chemotherapy ovarian cancer patients...
September 2, 2016: Cancer Research
Florian Weiland, Georgia Arentz, Manuela Klingler-Hoffmann, Peter McCarthy, Noor A Lokman, Gurjeet Kaur, Martin K Oehler, Peter Hoffmann
Although acetylation is regarded as a common protein modification, a detailed proteome wide profile of this posttranslational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimised a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis in order to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 341 N-terminally acetylated proteins, 23 of which are previously un-reported...
August 29, 2016: Journal of Proteome Research
Zaynab Al-Eisawi, Philip Beale, Charles Chan, Jun Qing Yu, Nicholas Proschogo, Mark Molloy, Fazlul Huq
BACKGROUND: The management of ovarian cancer remains a challenge. Because of the lack of early symptoms, it is often diagnosed at a late stage when it is likely to have metastasized beyond ovaries. Currently, platinum based chemotherapy is the primary treatment for the disease. However acquired drug resistance remains an on-going problem. As cisplatin brings about apoptosis by intrinsic and extrinsic pathways, this study aimed to determine changes in activity of platinum drugs when administered in two aliquots as against a bolus and sought to determine association with changes in GSH, speciation of platinum drugs and changes in protein expression...
2016: BMC Cancer
Jianhua Gao, Dan Liu, Jie Li, Qianlin Song, Qi Wang
Ovarian cancer is the main cause of cancer mortality in gynecological tumors around the world. Drug resistance to a variety of chemotherapeutics continue to be one of the main causes of treatment failure. In a previous study, it was demonstrated that STK17A, a proapoptotic gene, was significantly downregulated in acquired resistance phenotypes of colon cancer cells that are resistant to oxaliplatin and 5-fluorouracil. Therefore in the present study, the association between STK17A expression and ovarian cancer with initial drug resistance was investigated and the influence of STK17 on ovarian cancer cell proliferation and doubling time...
August 2016: Oncology Letters
Aparajitha Vaidyanathan, Lynne Sawers, Anne-Louise Gannon, Probir Chakravarty, Alison L Scott, Susan E Bray, Michelle J Ferguson, Gillian Smith
BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461...
August 9, 2016: British Journal of Cancer
Matthias B Stope, Luise Wiegank, Martin Weiss, Karoline Diesing, Dominique Koensgen, Martin Burchardt, Marek Zygmunt, Alexander Mustea
BACKGROUND: Heat-shock protein HSPB1 (alternative name HSP27) plays a pivotal role in cell survival pathways, apoptosis, metastasis and has been frequently linked to treatment resistance in ovarian cancer (OC) and other malignancies. Characteristic HSPB1 induction in different solid tumors is often caused by cytotoxic agents. MATERIALS AND METHODS: An in vitro OC cell model system was established to characterize resistance mechanisms during chemotherapy. Human OC cell lines OVCAR-3, SK-OV-3 and TOV-21G were treated with paclitaxel or carboplatin...
July 2016: Anticancer Research
Cong Zhou, Andrew Clamp, Alison Backen, Carlo Berzuini, Andrew Renehan, Rosamonde E Banks, Richard Kaplan, Stefan J Scherer, Gunnar B Kristensen, Eric Pujade-Lauraine, Caroline Dive, Gordon C Jayson
BACKGROUND: There is a critical need for predictive/resistance biomarkers for VEGF inhibitors to optimise their use. METHODS: Blood samples were collected during and following treatment and, where appropriate, upon progression from ovarian cancer patients in ICON7, a randomised phase III trial of carboplatin and paclitaxel with or without bevacizumab. Plasma concentrations of 15 circulating angio-biomarkers were measured using a validated multiplex ELISA, analysed through a novel network analysis and their relevance to the PFS then determined...
July 12, 2016: British Journal of Cancer
Chueh-Yi Huang, Yuh-Cheng Yang, Kung-Liahng Wang, Tze-Chien Chen, Jen-Ruei Chen, Chia-Sui Weng, Hung-Ju Chien, Chih-Long Chang
OBJECTIVE: To dissect the correlated hematologic markers that reflect the clinical outcome or treatment response in patients receiving dose-dense chemotherapy with a combination of platinum (cisplatin or carboplatin) and paclitaxel. MATERIALS AND METHODS: From 2009 to 2014, we enrolled 55 ovarian cancer patients (total 67 courses) including first-line, persistent, platinum-sensitive, or platinum-resistant disease in MacKay Memorial Hospital, Taipei, Taiwan. Weekly pretreatment complete blood counts and calculated ratios [platelet/neutrophil ratio, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), neutrophil/monocyte ratio, platelet/monocyte ratio, lymphocyte/monocyte ratio] during dose-dense chemotherapy were collected...
June 2016: Taiwanese Journal of Obstetrics & Gynecology
Yan Zhao, Qiaoyan Li, Xiaoying Wu, Puxiang Chen
Ovarian cancer has a poor prognosis due to its chemoresistance, and p27Kip1 (p27) has been implicated in tumor prognosis and drug-resistance. However, the regulatory mechanisms of p27 in drug‑resistance in ovarian cancer remain unknown. The current study successfully established chemoresistant cell lines using paclitaxel (TAX), cisplatin (DDP) and carboplatin (CBP) in SKOV3 ovarian cancer cells. The results indicated that the expression levels of p27 were dramatically downregulated in chemoresistant cells...
August 2016: Molecular Medicine Reports
Sofia-Paraskevi Trachana, Eleftherios Pilalis, Nikos G Gavalas, Kimon Tzannis, Olga Papadodima, Michalis Liontos, Alexandros Rodolakis, Georgios Vlachos, Nikolaos Thomakos, Dimitrios Haidopoulos, Maria Lykka, Konstantinos Koutsoukos, Efthimios Kostouros, Evagelos Terpos, Aristotelis Chatziioannou, Meletios-Athanasios Dimopoulos, Aristotelis Bamias
Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors...
2016: PloS One
Fernanda Musa, Amandine Alard, Gizelka David-West, John P Curtin, Stephanie V Blank, Robert J Schneider
There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K-AKT-mTOR pathway signaling, DNA damage and repair response (DDR) gene expression, and translational control were all investigated...
July 2016: Molecular Cancer Therapeutics
Åsa Fransson, Daria Glaessgen, Jessica Alfredsson, Klas G Wiman, Svetlana Bajalica-Lagercrantz, Nina Mohell
BACKGROUND: Mutation in the tumor suppressor gene TP53 is an early event in the development of high-grade serous (HGS) ovarian cancer and is identified in more than 96 % of HGS cancer patients. APR-246 (PRIMA-1(MET)) is the first clinical-stage compound that reactivates mutant p53 protein by refolding it to wild type conformation, thus inducing apoptosis. APR-246 has been tested as monotherapy in a Phase I/IIa clinical study in hematological malignancies and prostate cancer with promising results, and a Phase Ib/II study in combination with platinum-based therapy in ovarian cancer is ongoing...
2016: Journal of Ovarian Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"