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Platinum chemotherapy resistance

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https://www.readbyqxmd.com/read/27919980/intraperitoneal-chemotherapy-in-patients-pretreated-for-ovarian-cancer-matched-with-patients-treated-with-parenteral-chemotherapy
#1
Maria Ornella Nicoletto, Alessandra Casarin, Alessandra Baldoni, Eliana Rulli, Giulia Tasca, Zora Baretta, Grazia Artioli, Giuseppe Lombardi, Alessandro Cappetta, Irene Floriani, Giovanni Randon, Sara Valpione, Piero Litta, Pierfranco Conte, Simone Mocellin, Camillo Aliberti
BACKGROUND: Our aim was to analyze the impact of intraperitoneal chemotherapy (IPC), administered with direct peritoneal puncture, on the survival of patients with pretreated ovarian cancer in a real-life setting. PATIENTS AND METHODS: This was a retrospective study comparing patients with advanced ovarian cancer treated with IPC (N=33) and patients treated with standard intravenous (i.v.) chemotherapy matching cases for known prognostic factors (age, platinum sensitivity, histological subgroup and grade)...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27918136/development-of-cell-permeable-non-helical-constrained-peptides-to-target-a-key-protein-protein-interaction-in-ovarian-cancer
#2
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...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27914067/5q-syndrome-like-features-as-the-first-manifestation-of-myelodysplastic-syndrome-in-a-patient-with-an-unbalanced-whole-arm-translocation-der-5-19-p10-q10
#3
Hiroshi Ureshino, Haruna Kizuka, Kana Kusaba, Haruhiko Sano, Atsujiro Nishioka, Takero Shindo, Yasushi Kubota, Toshihiko Ando, Kensuke Kojima, Shinya Kimura
Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before...
December 2, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27903924/randomized-phase-ii-study-of-cabazitaxel-versus-methotrexate-in-patients-with-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-previously-treated-with-platinum-based-therapy
#4
Jean-Pascal Henry Machiels, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stéphanie Henry, Lionel D'Hondt, Christophe Lonchay, Stéphane Holbrechts, Petra Boegner, Dany Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Aline Gillain, Joelle Schoonjans, Sylvie Rottey
LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%)...
November 30, 2016: Oncologist
https://www.readbyqxmd.com/read/27903751/microdose-induced-drug-dna-adducts-as-biomarkers-of-chemotherapy-resistance-in-humans-and-mice
#5
Maike Zimmermann, Si-Si Wang, Hongyong Zhang, Tzu-Yin Lin, Michael Malfatti, Kurt Haack, Ted Ognibene, Hongyuan Yang, Susan Airhart, Kenneth W Turteltaub, George D Cimino, Clifford G Tepper, Alexandra Drakaki, Karim Chamie, Ralph de Vere White, Chong-Xian Pan, Paul T Henderson
We report progress on predicting tumor response to platinum-based chemotherapy with a novel mass spectrometry approach. Fourteen bladder cancer patients were administered one diagnostic microdose each of [14C]carboplatin (1% of the therapeutic dose). Carboplatin-DNA adducts were quantified by accelerator mass spectrometry (AMS) in blood and tumor samples collected within 24 hours, and compared to subsequent chemotherapy response. Patients with the highest adduct levels were responders, but not all responders had high adduct levels...
November 30, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27899771/-perspectives-of-individualized-treatment-by-genome-wide-analyses-in-ovarian-cancer
#6
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/27895753/drug-resistance-analysis-of-gefitinib-targeted-therapy-in-non-small-cell-lung-cancer
#7
Shuliang Liu, Hongji Yang, Xingping Ge, Lingfei Su, Aifeng Zhang, Liang Liang
The aim of the study was to examine the drug resistance analysis of gefitinib-targeted therapy in non-small cell lung cancer (NSCLC). In total, 156 NSCLC patients without surgical treatment were selected, including 117 cases of adenocarcinoma (75%), to receive single gefitinib 0.25 g/day or combined with platinum chemotherapy. Computed tomography was used to evaluate tumor growth for the response and non-response groups. The chemotherapy regimen was changed or combined with radiotherapy in the non-response group...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894751/polymerase-%C3%AE%C2%B5-pole-ultra-mutation-in-uterine-tumors-correlates-with-t-lymphocyte-infiltration-and-increased-resistance-to-platinum-based-chemotherapy-in-vitro
#8
Stefania Bellone, Eliana Bignotti, Silvia Lonardi, Francesca Ferrari, Floriana Centritto, Alice Masserdotti, Francesca Pettinella, Jonathan Black, Gulden Menderes, Gary Altwerger, Pei Hui, Salvatore Lopez, Christopher de Haydu, Elena Bonazzoli, Federica Predolini, Luca Zammataro, Emiliano Cocco, Federico Ferrari, Antonella Ravaggi, Chiara Romani, Fabio Facchetti, Enrico Sartori, Franco E Odicino, Dan-Arin Silasi, Babak Litkouhi, Elena Ratner, Masoud Azodi, Peter E Schwartz, Alessandro D Santin
OBJECTIVE: Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy. METHODS: Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14) 131 EC...
November 25, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27893326/randomized-prospective-biomarker-trial-of-ercc1-for-comparing-platinum-and-nonplatinum-therapy-in-advanced-non-small-cell-lung-cancer-ercc1-trial-et
#9
Siow Ming Lee, Mary Falzon, Fiona Blackhall, James Spicer, Marianne Nicolson, Abhro Chaudhuri, Gary Middleton, Samreen Ahmed, Jonathan Hicks, Barbara Crosse, Mark Napier, Julian M Singer, David Ferry, Conrad Lewanski, Martin Forster, Sally-Ann Rolls, Arrigo Capitanio, Robin Rudd, Natasha Iles, Yenting Ngai, Michael Gandy, Rachel Lillywhite, Allan Hackshaw
Purpose Retrospective studies indicate that expression of excision repair cross complementing group 1 (ERCC1) protein is associated with platinum resistance and survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the superiority of nonplatinum therapy over platinum doublet therapy for ERCC1-positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and Methods This trial had a marker-by-treatment interaction phase III design, with ERCC1 (8F1 antibody) status as a randomization stratification factor...
November 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27888804/niclosamide-and-its-analogs-are-potent-inhibitors-of-wnt-%C3%AE-catenin-mtor-and-stat3-signaling-in-ovarian-cancer
#10
Rebecca C Arend, Angelina I Londoño-Joshi, Abhishek Gangrade, Ashwini A Katre, Chandrika Kurpad, Yonghe Li, Rajeev S Samant, Pui-Kai Li, Charles N Landen, Eddy S Yang, Bertha Hidalgo, Ronald D Alvarez, J Michael Straughn, Andres Forero, Donald J Buchsbaum
Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer mortality worldwide. Platinum-based therapy is the standard first line treatment and while most patients initially respond, resistance to chemotherapy usually arises. Major signaling pathways frequently upregulated in chemoresistant cells and important in the maintenance of cancer stem cells (CSCs) include Wnt/β-catenin, mTOR, and STAT3. The major objective of our study was to investigate the treatment of ovarian cancer with targeted agents that inhibit these three pathways...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#11
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884789/surgery-for-advanced-epithelial-ovarian-cancer
#12
REVIEW
Neville F Hacker, Archana Rao
Cytoreductive surgery for patients with advanced epithelial ovarian cancer has been practised since the pioneering work of Tom Griffiths in 1975. Further research has demonstrated the prognostic significance of the extent of metastatic disease pre-operatively, and of complete cytoreduction post-operatively. Patients with advanced epithelial ovarian cancer should be referred to high volume cancer units, and managed by multidisciplinary teams. The role of thoracoscopy and resection of intrathoracic disease is presently investigational...
October 20, 2016: Best Practice & Research. Clinical Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/27878277/synthetic-paclitaxel-octreotide-conjugate-reverses-the-resistance-of-paclitaxel-in-a2780-taxol-ovarian-cancer-cell-line
#13
Yang Shen, Xiao-Yu Zhang, Xi Chen, Li-Li Fan, Mu-Lan Ren, Yong-Ping Wu, Kenneth Chanda, Shi-Wen Jiang
The high mortality of ovarian cancer is partly due to the frequent resistance of ovarian cancer to current chemotherapy agents such as paclitaxel and platinum. Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some tumors through binding to somatostatin receptor (SSTR) and activation of Ras-, Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor growth inhibition with reduced toxicity...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27877224/the-role-of-copper-transporter-atp7a-in-platinum-resistance-of-esophageal-squamous-cell-cancer-escc
#14
Zhuang-Hua Li, Rongjie Zheng, Jing-Tang Chen, Jun Jia, Miaozhen Qiu
Purpose: Platinum derivatives, such as cisplatin (DDP), carboplatin and oxaliplatin, are widely used components of modern cancer chemotherapy including esophageal squamous cell cancer (ESCC). However, their roles are limited by the impact of intrinsic/acquired resistance mechanisms on tumor responses. Recent studies have shown that the mammalian copper transporters CTR1, ATP7A and ATP7B are involved in cisplatin-resistance to some cancers. Methods: The cytotoxicities of DDP in different cell lines were determined using the MTT assay...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27871723/safety-and-efficacy-of-single-agent-bevacizumab-containing-therapy-in-elderly-patients-with-platinum-resistant-recurrent-ovarian-cancer-subgroup-analysis-of-the-randomised-phase-iii-aurelia-trial
#15
Roberto Sorio, Célia Roemer-Becuwe, Felix Hilpert, Emma Gibbs, Yolanda García, Janne Kaern, Manon Huizing, Petronella Witteveen, Flora Zagouri, David Coeffic, Hans-Joachim Lück, Antonio González-Martín, Gunnar Kristensen, Charles-Briac Levaché, Chee Khoon Lee, Val Gebski, Eric Pujade-Lauraine
BACKGROUND: The AURELIA trial demonstrated significantly improved progression-free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant ovarian cancer (PROC). METHODS: Patients with PROC were randomised to receive investigator-selected single-agent chemotherapy alone or with bevacizumab. Post-hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes according to age <65 versus ≥65years. RESULTS: In the 133 patients (37%) aged ≥65years, baseline hypertension was more frequent and ascites was less common than in patients <65years...
November 18, 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27855386/conversion-of-platinum-etoposide-resistant-to-sensitive-sclc-after-treatment-with-the-epi-immunotherapeutic-rrx-001-a-case-report
#16
Christina Brzezniak, Bryan Oronsky, Jan Scicinski, Scott Caroen, Pedro Cabrales, Nacer Dean Abrouk, Michelle M Kim, James F Brown, Tony R Reid, Christopher Larson, Arnold Oronsky, Regina Day, Aiste Degesys, Corey A Carter
BACKGROUND: The response to first-line platinum doublets (cisplatin/etoposide) in small-cell lung cancer (SCLC) predicts the probability of subsequent response to second-line therapy. In general, the longer-lived the responses in first line, the better the outcome in second line, with the opposite prognosis for shorter-lived responses. Resistant SCLC is defined as relapse within 90 days of platinum-doublet treatment, and predictably correlates with shortened survival compared with sensitive disease, defined as relapse after 90 days...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27855385/prognostic-significance-of-preoperative-prognostic-nutritional-index-in-epithelial-ovarian-cancer-patients-treated-with-platinum-based-chemotherapy
#17
Yi Miao, Shuangdi Li, Qin Yan, Bilan Li, Youji Feng
BACKGROUND: The aim of present study was to investigate the role of the prognostic nutritional index (PNI) used as a prognostic marker for predicting response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. PATIENTS AND METHODS: Patients with a new diagnosis of EOC receiving postoperative platinum-based chemotherapy were identified. The PNI was calculated as 10 × serum albumin value (g/dl) + 0...
2016: Oncology Research and Treatment
https://www.readbyqxmd.com/read/27852039/bevacizumab-in-ovarian-cancer-a-critical-review-of-phase-iii-studies
#18
REVIEW
Luigi Rossi, Monica Verrico, Eleonora Zaccarelli, Anselmo Papa, Maria Colonna, Martina Strudel, Patrizia Vici, Vincenzo Bianco, Federica Tomao
Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27843619/immune-checkpoint-blockade-in-small-cell-lung-cancer-is-there-a-light-at-the-end-of-the-tunnel
#19
REVIEW
Luca Paglialunga, Zena Salih, Biagio Ricciuti, Raffaele Califano
Small cell lung cancer (SCLC) is a very aggressive disease, characterised by rapid growth, high response rates to both chemotherapy and radiotherapy and subsequent development of treatment resistance in the vast majority of patients. In the past 30 years, little progress has been made in systemic treatments and the established management paradigm of platinum-based chemotherapy has reached an efficacy plateau. Several clinical trials have investigated targeted therapies, without producing clinically significant benefits...
2016: ESMO Open
https://www.readbyqxmd.com/read/27843207/chemotherapy-options-in-castration-resistant-prostate-cancer
#20
REVIEW
Benjamin A Teply, Ralph J Hauke
INTRODUCTION: The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC) is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy. Chemotherapy remains an essential component of the armamentarium. Herein, we review current chemotherapy options for patients with CRPC and discuss future challenges. METHODS: We reviewed literature for chemotherapy agents in prostate cancer, with special attention to the evidence for efficacy of the currently approved agents...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
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