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https://www.readbyqxmd.com/read/29316077/cellular-stress-induces-cancer-stem-like-cells-through-expression-of-dnajb8-by-activation-of-hsf1
#1
Hiroki Kusumoto, Yoshihiko Hirohashi, Satoshi Nishizawa, Masamichi Yamashita, Kazuyo Yasuda, Aiko Murai, Akari Takaya, Takashi Mori, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Toru Kondo, Noriyuki Sato, Isao Hara, Toshihiko Torigoe
In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) and that it has a role in the maintenance of kidney CSCs/CICs. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In this study, we therefore examined whether heat shock (HS) induces CSCs/CICs. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells...
January 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29313954/phase-1-2-trial-of-temsirolimus-and-sorafenib-in-the-treatment-of-patients-with-recurrent-glioblastoma-north-central-cancer-treatment-group-study-alliance-n0572
#2
David Schiff, Kurt A Jaeckle, S Keith Anderson, Evanthia Galanis, Caterina Giannini, Jan C Buckner, Phillip Stella, Patrick J Flynn, Bradley J Erickson, John F Schwerkoske, Vesna Kaluza, Erin Twohy, Janet Dancey, John Wright, Jann N Sarkaria
BACKGROUND: Mitogen-activated protein kinase (MAPK) activation and mammalian target of rapamycin (mTOR)-dependent signaling are hallmarks of glioblastoma. In the current study, the authors conducted a phase 1/2 study of sorafenib (an inhibitor of Raf kinase and vascular endothelial growth factor receptor 2 [VEGFR-2]) and the mTOR inhibitor temsirolimus in patients with recurrent glioblastoma. METHODS: Patients with recurrent glioblastoma who developed disease progression after surgery or radiotherapy plus temozolomide and with ≤2 prior chemotherapy regimens were eligible...
January 3, 2018: Cancer
https://www.readbyqxmd.com/read/29300804/a-phase-ii-study-of-temsirolimus-added-to-low-dose-weekly-carboplatin-and-paclitaxel-for-patients-with-recurrent-and-or-metastatic-r-m-head-and-neck-squamous-cell-carcinoma-hnscc
#3
L A Dunn, M G Fury, H Xiao, S S Baxi, E J Sherman, S Korte, C Pfister, S Haque, N Katabi, A L Ho, D G Pfister
No abstract text is available yet for this article.
January 2, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29299126/hdac-inhibition-as-a-treatment-concept-to-combat-temsirolimus-resistant-bladder-cancer-cells
#4
Eva Juengel, Ramin Najafi, Jochen Rutz, Sebastian Maxeiner, Jasmina Makarevic, Frederik Roos, Igor Tsaur, Axel Haferkamp, Roman A Blaheta
Introduction: Although the mechanistic target of rapamycin (mTOR) might be a promising molecular target to treat advanced bladder cancer, resistance develops under chronic exposure to an mTOR inhibitor (everolimus, temsirolimus). Based on earlier studies, we proposed that histone deacetylase (HDAC) blockade might circumvent resistance and investigated whether HDAC inhibition has an impact on growth of bladder cancer cells with acquired resistance towards temsirolimus. Results: The HDAC inhibitor valproic acid (VPA) significantly inhibited growth, proliferation and caused G0/G1 phase arrest in RT112res and UMUC-3res...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285361/response-to-nivolumab-in-metastatic-collecting-duct-carcinoma-expressing-pd-l1-a-case-report
#5
Kosuke Mizutani, Kengo Horie, Shingo Nagai, Tomohiro Tsuchiya, Chiemi Saigo, Kazuhiro Kobayashi, Tatsuhiko Miyazaki, Takashi Deguchi
The authors present a case report of collecting duct carcinoma (CDC) that responded to nivolumab, a programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, following the failure of systemic treatment with chemotherapy and targeted therapy. The patient underwent right radical nephrectomy and segmentectomy of the lung following chemotherapy. Fifteen months following the first surgery, segmentectomy and subsequent second-line chemotherapy were performed for recurrence in the lung. Targeted therapy with temsirolimus for recurrence of the lung and lymph node metastases was ultimately used for 30 months...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29228590/precision-and-recall-oncology-combining-multiple-gene-mutations-for-improved-identification-of-drug-sensitive-tumours
#6
Stefan Naulaerts, Cuong C Dang, Pedro J Ballester
Cancer drug therapies are only effective in a small proportion of patients. To make things worse, our ability to identify these responsive patients before administering a treatment is generally very limited. The recent arrival of large-scale pharmacogenomic data sets, which measure the sensitivity of molecularly profiled cancer cell lines to a panel of drugs, has boosted research on the discovery of drug sensitivity markers. However, no systematic comparison of widely-used single-gene markers with multi-gene machine-learning markers exploiting genomic data has been so far conducted...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29225833/longer-recurrence-free-survival-in-a-patient-with-metastatic-renal-cell-carcinoma-treated-with-temsirolimus
#7
Tendo Satoh, Takuya Koie, Hirotaka Horiguchi, Noriko Tokui, Satoshi Narita, Chikara Ohyama
Temsirolimus did not demonstrate an efficacy advantage compared with sorafenib as second-line therapy in patients with metastatic renal cell carcinoma (mRCC). Only a few patients achieved complete responses, and the median progression-free survival rate remains short. We report one patient with mRCC who had a continuing response to temsirolimus.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29200680/poor-risk-advanced-renal-cell-carcinoma-outcomes-from-a-registry-in-a-tertiary-cancer-center
#8
Anant Ramaswamy, Amit Joshi, Vanita Noronha, Vijay Patil, Arvind Sahu, Deepan R Manickam, Rushabh Kothari, Nilesh Sable, Archi Agrawal, Santosh Menon, Kumar Prabhash
Background: Poor-risk advanced Renal cell carcinoma (RCC) are an under-evaluated and difficult to treat subset of patients with poor prognosis. While Temsirolimus is the approved first line therapy for this category, Tyrosine kinase inhibitors (TKIs) are also commonly uses as initial treatment. We present an analysis of poor-risk advanced RCC treated in our institute. Materials and Methods: Patients diagnosed as poor-risk (as per Heng criteria) advanced RCC from June 2008 to December 2015 were analysed for baseline demographics, treatment received, toxicity (primarily Grade 3 and Grade 4), response rates (RR) and survival...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29198329/examining-the-bleeding-incidences-associated-with-targeted-therapies-used-in-metastatic-renal-cell-carcinoma
#9
REVIEW
MacKenzie Crist, Elizabeth Hansen, Lipika Chablani, Elizabeth Guancial
A systematic review was conducted to illustrate the bleeding risks associated with targeted therapies used in the treatment of metastatic renal cell carcinoma (mRCC). Eligible studies included phase II, III, or IV clinical trials using pazopanib, sunitinib, cabozantinib, lenvatinib, everolimus, temsirolimus, bevacizumab, axitinib, and/or sorafenib in the setting of mRCC. Types of bleeding event(s), bleeding event frequency, and incidence of thrombocytopenia were collected from the relevant articles. ClinicalTrials...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29198077/fibroblast-like-synoviocyte-migration-is-enhanced-by-il-17-mediated-overexpression-of-l-type-amino-acid-transporter-1-lat1-via-the-mtor-4e-bp1-pathway
#10
Zhao Yu, Wang Lin, Zhang Rui, Pan Jihong
In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH...
December 2, 2017: Amino Acids
https://www.readbyqxmd.com/read/29195016/association-of-high-cost-sharing-and-targeted-therapy-initiation-among-elderly-medicare-patients-with-metastatic-renal-cell-carcinoma
#11
Pengxiang Li, Yu-Ning Wong, Jordan Jahnke, Amy R Pettit, Jalpa A Doshi
High out-of-pocket costs may limit access to oral therapies covered by patients' prescription drug benefits. We explored financial barriers to treatment initiation in patients newly diagnosed with metastatic renal cell carcinoma (mRCC) by comparing Medicare Part D patients with low out-of-pocket costs due to receipt of full low-income subsidies (LIS beneficiaries) to their counterparts who were responsible for more than 25% cost sharing during Medicare's initial coverage phase (non-LIS beneficiaries). We used 2011-2013 100% Medicare claims for non-LIS and LIS beneficiaries newly diagnosed with metastases in the liver, lung, or bone to examine targeted therapy treatment initiation rates and time to initiation for (1) oral medications (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) covered under Medicare's prescription drug benefit (Part D); (2) injected or infused medications (temsirolimus or bevacizumab) covered by Medicare's medical benefit (Part B); and (3) any (Part D or Part B) targeted therapy...
December 1, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29178153/global-transition-of-human-serum-albumin-to-prefibrillar-aggregates-induced-by-temsirolimus-insight-into-implications-of-anti-renal-cancer-drug
#12
Anas Shamsi, Azaj Ahmed, Bilqees Bano
In our study, we have characterized the prefibrillar aggregates of human serum albumin (HSA) induced by temsirolimus, anti-renal cancer drug. Molecular docking was retorted to confirm binding of HSA and temsirolimus. Temsirolimus caused the structural transition of native HSA to non-native species after prolonged incubation of 20 days. These non-native species were characterized as prefibrillar aggregates as evident by decreased intrinsic fluorescence and enhanced 8-anilino-1-naphthalene-sulphonic acid (ANS) fluorescence...
November 27, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29172868/treatment-for-patients-with-relapsed-refractory-mantle-cell-lymphoma-european-based-recommendations
#13
Martin Dreyling, Igor Aurer, Sergio Cortelazzo, Olivier Hermine, Georg Hess, Mats Jerkeman, Steven Le Gouill, Vincent Ribrag, Marek Trněný, Carlo Visco, Jan Walewski, Francesco Zaja, Pier Luigi Zinzani
Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed...
November 27, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29156834/oncolytic-reovirus-inhibits-angiogenesis-through-induction-of-cxcl10-ip-10-and-abrogation-of-hif-activity-in-soft-tissue-sarcomas
#14
Jennifer S Carew, Claudia M Espitia, Weiguo Zhao, Monica M Mita, Alain C Mita, Steffan T Nawrocki
The tumor-selective viral replication capacity and pro-apoptotic effects of oncolytic reovirus have been reported to be dependent on the presence of an activated RAS pathway in several solid tumor types. However, the mechanisms of selective anticancer efficacy of the reovirus-based formulation for cancer therapy (Reolysin, pelareorep) have not been rigorously studied in soft tissue sarcomas (STS). Here we report that Reolysin triggered a striking induction of the anti-angiogenic chemokine interferon-γ-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) in both wild type and RAS mutant STS cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118224/exceptional-response-to-temsirolimus-in-a-metastatic-clear-cell-renal-cell-carcinoma-with-an-early-novel-mtor-activating-mutation
#15
Juan Francisco Rodríguez-Moreno, María Apellaniz-Ruiz, Juan María Roldan-Romero, Ignacio Durán, Luis Beltrán, Cristina Montero-Conde, Alberto Cascón, Mercedes Robledo, Jesus García-Donas, Cristina Rodríguez-Antona
mTOR pathway inhibitors are important drugs for the treatment of advanced renal cell carcinoma (RCC). However, no valid predictive markers have been identified to guide treatment selection and identify patients who are sensitive to these drugs. Mutations activating the mTOR pathway have been suggested to predict response; however, their predictive value is still unclear. Here, we present the genomic and functional characterization of a patient with metastatic clear cell RCC (ccRCC) who experienced a partial response to temsirolimus after a poor response to 2 previous lines of treatment...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29103764/additive-cytotoxic-effects-of-radiation-and-mtor-inhibitors-in-a-cervical-cancer-cell-line
#16
Daniele Xavier Assad, Gabriel Alvares Borges, Samuel Ramalho Avelino, Eliete Neves Silva Guerra
The PI3K/AKT/mTOR signaling pathway is frequently activated in HPV-positive cervical squamous cell cancer (CC). This study investigated the biological effects of mTOR inhibitors associated with radiotherapy in a CC cell line (HeLa). A human keratinocyte cell line (HaCaT) was used as control. Temsirolimus, everolimus, resveratrol, curcumin and epigallocatechin gallate (EGCG) were the mTOR inhibitors assessed. The 50% cell cytotoxicity rate (CC50) for each treatment was determined by MTT cell viability assay...
November 2, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29103175/efficacy-and-safety-in-older-patient-subsets-in-studies-of-endocrine-monotherapy-versus-combination-therapy-in-patients-with-hr-her2-%C3%A2-advanced-breast-cancer-a-review
#17
REVIEW
Rachel A Freedman, Sara M Tolaney
PURPOSE: Prospective information regarding the tolerability and efficacy of endocrine therapy (ET) alone and in combination with targeted agents in older patients in the metastatic setting is limited. This review summarizes available trial data in this population. METHODS: We searched PubMed for Phase 2 or 3 trials with age-stratified patient cohorts (≥ 65 vs. < 65 years in most studies) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer treated with ET ± targeted agents...
November 4, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/29074560/a-network-meta-analysis-of-short-term-efficacy-of-different-single-drug-targeted-therapies-in-the-treatment-of-renal-cell-carcinoma
#18
Hong-Ling He, Wan-Xia Yao
The network meta-analysis was conducted to compare the short-term efficacy of different single-drug targeted therapies in the treatment of renal cell carcinoma (RCC). We initially searched databases for randomized controlled trials (RCTs) on different single-drug targeted therapies in treating RCC. The meta-analysis combined the direct and indirect evidence to calculate the pooled odds ratios (OR) and draw surface under the cumulative ranking curves (SUCRA). A total of 14 eligible RCTs were ultimately selected...
October 26, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28961834/a-phase-ii-study-of-temsirolimus-added-to-low-dose-weekly-carboplatin-and-paclitaxel-for-patients-with-recurrent-and-or-metastatic-r-m-head-and-neck-squamous-cell-carcinoma-hnscc
#19
L A Dunn, M G Fury, H Xiao, S S Baxi, E J Sherman, S Korte, C Pfister, S Haque, N Katabi, A L Ho, D G Pfister
Background: Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy. Patients and methods: In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28952411/clinical-development-of-mtor-inhibitors-for-renal-cancer
#20
REVIEW
Michele Ghidini, Fausto Petrelli, Antonio Ghidini, Gianluca Tomasello, Jens Claus Hahne, Rodolfo Passalacqua, Sandro Barni
Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. In the last 10 years, clinical trials have established multitargeted tyrosine kinase inhibitors (TKIs) as the standard first-line treatment in patients with metastatic disease. Multiple agents are now available for treatment in subsequent lines.The mammalian target of rapamycin (mTOR) inhibitors (e.g., everolimus alone or with lenvatinib) are among the most effective options. Areas covered: This paper provides a complete and updated overview on mTOR inhibitors for the treatment of advanced RCC...
November 2017: Expert Opinion on Investigational Drugs
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