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Platinum chemotherapy resistance

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
Tushar Tomar, Steven de Jong, Nicolette G Alkema, Rieks L Hoekman, Gert Jan Meersma, Harry G Klip, Ate Gj van der Zee, G Bea A Wisman
BACKGROUND: In high-grade serous ovarian cancer (HGSOC), intrinsic and/or acquired resistance against platinum-containing chemotherapy is a major obstacle for successful treatment. A low frequency of somatic mutations but frequent epigenetic alterations, including DNA methylation in HGSOC tumors, presents the cancer epigenome as a relevant target for innovative therapy. Patient-derived xenografts (PDXs) supposedly are good preclinical models for identifying novel drug targets. However, the representativeness of global methylation status of HGSOC PDXs compared to their original tumors has not been evaluated so far...
October 20, 2016: Genome Medicine
Kensuke Hori, Tomohiko Tsuruta, Chihiro Odani, Hitomi Ono, Rieko Ohkubo, Kanoko Shimoji, Junko Murakami, Mio Nakagawa, Lina Tashima, Kimihiko Ito
OBJECTIVES: Treatment for ovarian cancer with bevacizumab(Bmab)has been covered by public medical insurance in Japan since November 2013. It is recommended that the use of Bmab is limited to the first treatment for FIGO stage III or IV ovarian cancer. The OCEAN trial for platinum sensitivity in relapsed patients and the AURELIA trial for platinum-resistance in relapsed patients were performed, and both significantly improved progression-free survival. METHOD: We retrospectively studied patients receiving Bmab with an anticancer agent for recurrent ovarian cancer...
October 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Flaria El Khoury, Laurent Corcos, Stéphanie Durand, Brigitte Simon, Catherine Le Jossic-Corcos
Colorectal cancer (CRC) is one of the most aggressive cancers worldwide. Several anticancer agents are available to treat CRC, but eventually cancer relapse occurs. One major cause of chemotherapy failure is the emergence of drug-resistant tumor cells, suspected to originate from the stem cell compartment. The aim of this study was to ask whether drug resistance was associated with the acquisition of stem cell-like properties. We isolated drug-resistant derivatives of two human CRC cell lines, HT29 and HCT116, using two anticancer drugs with distinct modes of action, oxaliplatin and docetaxel...
October 7, 2016: International Journal of Oncology
Hsien-Jen Cheng, Te-Haw Wu, Chih-Te Chien, Hai-Wei Tu, Ting-Shan Cha, Shu-Yi Lin
Despite nanoparticulate platinum (nano-Pt) has been validated to be acting as a platinum-based prodrug for anticancer therapy, the key factor in controlling its cytotoxicity remains to be clarified. In this study, it is found that the corrosion susceptibility of nano-Pt can be triggered by inducing the oxidization of superficial Pt atoms, which can kill both cisplatin-sensitive/resistance cancer cells. Direct evidence in the oxidization of superficial Pt atoms is validated to observe the formation of platinum oxides by X-ray absorption spectroscopy...
September 22, 2016: Small
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
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
Amy L Shafrir, Ana Babic, Rulla M Tamimi, Bernard A Rosner, Shelley S Tworoger, Kathryn L Terry
BACKGROUND: Ovarian cancer survival is poor, particularly for platinum-resistant cases. The previous literature on pre-diagnostic reproductive factors and ovarian cancer survival has been mixed. Therefore, we evaluated pre-diagnostic reproductive and hormonal factors with overall survival and, additionally, platinum-chemotherapy resistance. METHODS: We followed 1649 invasive epithelial ovarian cancer cases who were enrolled between 1992 and 2008 for overall mortality within the New England Case-Control Study and abstracted chemotherapy data on a subset (n=449)...
October 4, 2016: British Journal of Cancer
Ana Vanessa Nascimento, Amit Singh, Hassan Bousbaa, Domingos Ferreira, Bruno Sarmento, Mansoor M Amiji
: Efficiency of chemotherapy is often limited by low therapeutic index of the drug as well as emergence of inherent and acquired drug resistance in cancer cells. As a common strategy to overcome drug resistance, higher doses of chemo-agents are administered. However, adverse side effects are usually increased as a consequence. A potentially effective approach is to combine chemotherapy with other therapeutic strategies such as small interfering RNAs (siRNAs) that allow the use of lower yet efficient doses of the anticancer drugs...
September 30, 2016: Acta Biomaterialia
Sohei Matsumura, Tsuyoshi Ohta, Keiko Yamanouchi, Zhiyang Liu, Takeshi Sudo, Takanobu Kojimahara, Manabu Seino, Megumi Narumi, Seiji Tsutsumi, Toshifumi Takahashi, Kazuhiro Takahashi, Hirohisa Kurachi, Satoru Nagase
Activation of Estrogen receptor (ER) alpha (α) promotes cell growth and influences the response of cancer cell to chemotherapeutic agents. However, the mechanism by which ERα activation antagonizes cells to chemotherapy-induced cytotoxicity remains unclear. Here, we investigated the effect of cisplatin on ERα activation. In addition, we examined whether down-regulation of ERα modulate cisplatin-mediated cytotoxicity using two human ovarian cancer cells (Caov-3 and Ovcar-3) transduced with ERα short hairpin RNA (shRNA)...
September 30, 2016: Cancer Biology & Therapy
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
Imogen A Riddell, Keli Agama, Ga Young Park, Yves Pommier, Stephen J Lippard
Drugs capable of trapping topoisomerase II (Top2), an essential enzyme that cleaves DNA to remove naturally occurring knots and tangles, can serve as potent anticancer agents. The monofunctional platinum agent phenanthriplatin, cis-[Pt(NH3)2(phenanthridine)Cl](NO3), is shown here to trap Top2 in addition to its known modes of inhibition of DNA and RNA polymerases. Its potency therefore combines diverse modes of action by which phenanthriplatin kills cancer cells. The observation that phenanthriplatin can act as a Top2 poison highlights opportunities to design nonclassical platinum anticancer agents with this novel mechanism of action...
October 6, 2016: ACS Chemical Biology
Bin Ai, Zhixin Bie, Shuai Zhang, Ailing Li
Ovarian cancer is one of the gynecologic cancers with the highest mortality, wherein vascular endothelial growth factor (VEGF) is involved in regulating tumor vascularization, growth, migration, and invasion. VEGF-mediated angiogenesis in tumors has been targeted in various cancer treatments, and anti-VEGF therapy has been used clinically for treatment of several types of cancer. Paclitaxel is a natural antitumor agent in the standard front-line treatment that has significant efficiency to treat advanced cancers, including ovarian cancer...
2016: American Journal of Cancer Research
G Santabarbara, P Maione, A Rossi, G Palazzolo, C Gridelli
INTRODUCTION: Lung cancers remain the principal cause of death cancer-related worldwide with a poor survival rate at five years from diagnosis. In patients with NSCLC harboring specific genetic alterations the anti EGFR TKIs and the ALK TKIs have improved the response rate and the quality of life compared to standard platinum-based chemotherapy. New approaches possibly applicable at the major of patients are needed. AREAS COVERED: The discovery that the immune system plays a fundamental role in the fight against cancer...
September 23, 2016: Expert Review of Clinical Pharmacology
Brittany N Bahamon, Feng Gao, Hadi Danaee
Context .- Excision repair cross-complementation 1 (ERCC1) is a key enzyme in nuclear excision repair pathway and has a critical role in helping remove DNA adducts caused by cross-linking agents, such as platinum-containing cancer chemotherapies and other DNA-damaging therapeutic modalities. ERCC1 expression, evaluated by techniques such as immunohistochemistry, has been associated with clinical response; ERCC1(+) tumors are more resistant to cisplatin treatment than are ERCC1(-) tumors. Although several immunohistochemistry, anti-ERCC1 antibodies are available, the 8F1 clone, in particular, has been used in many studies...
September 9, 2016: Archives of Pathology & Laboratory Medicine
Muhammad Sirajuddin, Saqib Ali
Medicinal inorganic chemistry plays an important role in exploring the properties of metal ions for the designing of new drugs. The field has been stimulated by the success of cis-platin, the worldbest selling anticancer drug and platinum complexes with reduced toxicity, oral activity and activity against resistant tumors are currently on clinical trial. The use of cis-platin is, however, severely limited by its toxic side-effects. This has stimulated chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action...
September 6, 2016: Current Pharmaceutical Design
Yanlin Luo, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Yong Sang Song
It remains controversial whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) induces chemoresistance in advanced epithelial ovarian cancer (EOC) compared with primary debulking surgery (PDS). The aim of this study was to compare platinum-resistant recurrence following treatment with NACT-IDS or PDS in patients with stage IIIC and IV EOC.We retrospectively reviewed the records of 341 patients who underwent PDS or NACT-IDS for Federation of Gynecology and Obstetrics stage IIIC or IV EOC between March 1990 and December 2010...
September 2016: Medicine (Baltimore)
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
Gina L Westhoff, Katherine C Fuh, Terry A Longacre, Jennifer Leah McNally, I-Chow Hsu, Daniel S Kapp, Nelson Teng, Lee-May Chen
OBJECTIVE: Given the relative chemo-resistant nature of clear-cell gynecologic cancers, we investigated the utility of radiation therapy (RT) to treat recurrent clear-cell carcinoma (CCC) of the ovary. METHODS: A retrospective chart review of patients with recurrent CCC managed from 1994-2012 was conducted at 2 academic medical centers. Demographic and clinicopathologic factors were abstracted and evaluated using Pearson χ or t tests, Kaplan-Meier and Cox regression analyses...
August 29, 2016: International Journal of Gynecological Cancer
Michael T Zimmermann, Guoqian Jiang, Chen Wang
Platinum-based chemotherapies are first-line treatments for ovarian cancer (OC) patients. Although chemotherapy has a high initial response rate, some patients exhibit inherent chemo-resistance. With advancements of molecular and genomic profiling, it is of high interest to identify molecular and genomic signatures predictive of chemo- sensitivity priori to treatment initiation in order to better personalize care decisions. Previous efforts have made use of mRNA expression levels of selected genes responsible for repairing DNA damage, under the hypothesis that chemo efficacy is associated with their proficiency...
2016: AMIA Summits on Translational Science Proceedings
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