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Platinum resistance

Alexander Reinthaller
Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied antiangiogenic agent, bevacizumab - a monoclonal humanized antibody against vascular endothelial growth factor - was effective in all phases of the disease (first-line therapy, platinum-sensitive and platinum-resistant recurrence)...
2016: Memo
H Y Tian, P Yu, C Y Yuan, W Zhang, Y X Qiu, D H Li, X J Liang, X Y Wang
OBJECTIVE: To compare the durability of resin-based root-surface coating material and all-in-one self-etching adhesive on root surface in vitro. METHODS: Human extracted premolars or molars with intact roots were selected. The cementum was removed using a periodontal scaler to expose root dentin. The root surface was coated with an acid-resistant nail varnish, leaving a window of 3 mm×3 mm on the exposed dentin.The window was covered with either PRG Barrier Coat (PRG) or Clearfil S3 Bond (CS3)...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Kaitlin A Doucette, Kelly N Hassell, Debbie C Crans
Improving efficacy and lowering resistance to metal-based drugs can be addressed by consideration of the coordination complex speciation and key reactions important to vanadium antidiabetic drugs or platinum anticancer drugs under biological conditions. The methods of analyses vary depending on the specific metal ion chemistry. The vanadium compounds interconvert readily, whereas the reactions of the platinum compounds are much slower and thus much easier to study. However, the vanadium species are readily differentiated due to vanadium complexes differing in color...
October 3, 2016: Journal of Inorganic Biochemistry
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
Zhentong Wei, Yan Liu, Yishu Wang, Yandong Zhang, Qinghua Luo, Xiaxia Man, Feng Wei, Xiaowei Yu
Ovarian cancer (OVCa) stem cells are associated with tumor growth, metastasis, and recurrence, which are driving forces behind a majority of the OVCa-related mortality. This subpopulation of cancer cells are characterized by uncontrolled proliferation, high invasiveness, and resistance against the current platinum-based therapy. Thus, targeting OVCa cancer stem cells has been focused in recent therapeutic development. Isolation and purification of cancer stem cells are, however, challenging for the lack of sensitive and specific markers...
November 2016: Medical Oncology
Zhigang Wang, Zoufeng Xu, Guangyu Zhu
DNA damage response plays a key role not only in maintaining genome integrity but also in mediating the antitumor efficacy of DNA-damaging antineoplastic drugs. Herein, we report the rational design and evaluation of a Pt(IV) anticancer prodrug inhibiting nucleotide excision repair (NER), one of the most pivotal processes after the formation of cisplatin-induced DNA damage that deactivates the drug and leads to drug resistance in the clinic. This dual-action prodrug enters cells efficiently and causes DNA damage while simultaneously inhibiting NER to promote apoptotic response...
October 13, 2016: Angewandte Chemie
Hiroshi Suga, Hiroya Suzuki, Yuma Shinomura, Shota Kashiwabara, Kazuhito Tsukagoshi, Tetsuo Shimizu, Yasuhisa Naitoh
Highly stable, nonvolatile, high-temperature memory based on resistance switching was realized using a polycrystalline platinum (Pt) nanogap. The operating temperature of the memory can be drastically increased by the presence of a sharp-edged Pt crystal facet in the nanogap. A short distance between the facet edges maintains the nanogap shape at high temperature, and the sharp shape of the nanogap densifies the electric field to maintain a stable current flow due to field migration. Even at 873 K, which is a significantly higher temperature than feasible for conventional semiconductor memory, the nonvolatility of the proposed memory allows stable ON and OFF currents, with fluctuations of less than or equal to 10%, to be maintained for longer than eight hours...
October 11, 2016: Scientific Reports
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
Alberto A Chiappori, Gregory A Otterson, Afshin Dowlati, Anne M Traynor, Leora Horn, Taofeek K Owonikoko, Helen J Ross, Christine L Hann, Taher Abu Hejleh, Jorge Nieva, Xiuhua Zhao, Michael Schell, Daniel M Sullivan
LESSONS LEARNED: Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients...
October 2016: Oncologist
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
Xiao-Fei Zhang, Le Ou-Yang, Xing-Ming Zhao, Hong Yan
Understanding how the structure of gene dependency network changes between two patient-specific groups is an important task for genomic research. Although many computational approaches have been proposed to undertake this task, most of them estimate correlation networks from group-specific gene expression data independently without considering the common structure shared between different groups. In addition, with the development of high-throughput technologies, we can collect gene expression profiles of same patients from multiple platforms...
September 28, 2016: Scientific Reports
Anna Escolà, Margarita Crespo, Concepción López, Josefina Quirante, Anusha Jayaraman, Ibrahim H Polat, Josefa Badía, Laura Baldomà, Marta Cascante
A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma (A-549 lung, HCT-116 colon, and MCF-7 breast) cell lines and the normal bronquial epithelial BEAS-2B cells. Cathodic reduction potentials (shifting from -1.463 to -1.570V) reveal that the platinum(IV) compounds under study would be highly reluctant to be reduced in a biological environment...
September 15, 2016: Bioorganic & Medicinal Chemistry
Jian Gao, Camilla H Ulekleiv, Trond S Halstensen
BACKGROUND: Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to prognosis and cisplatin resistance, and if so, which ligand was most important and how was the expression regulated. METHODS: To examine the prognostic effect of EGFR-ligand expression, we analyzed tumorous mRNA expression in 399 HNSCC patients...
September 26, 2016: Journal of Experimental & Clinical Cancer Research: CR
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
John A Martignetti, Ying Chen, Catalina Camacho, Thomas R Silvers, Albiruni R A Razak, Nashat Y Gabrail, John F Gerecitano, Eva Kalir, Elena Pereira, Brad R Evans, Susan J Ramus, Fei Huang, Nolan Priedigkeit, Estefania Rodriguez, Michael Donovan, Faisal M Khan, Tamara Kalir, Robert P Sebra, Andrew Uzilov, Rong Chen, Rileen Sinha, Richard Halpert, Jean-Noel Billaud, Sharon Shacham, Dilara McCauley, Yosef Landesman, Tami Rashal, Michael Kauffman, Mansoor R Mirza, Morten Mau-Sørensen, Peter Dottino
PURPOSE: Ovarian cancer's (OvCa) high fatality-to-case ratio is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum sensitive and resistant OvCa. EXPERIMENTAL DESIGN: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO data sets and tissue microarrays (TMAs)...
September 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer 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
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