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https://www.readbyqxmd.com/read/29456880/cost-effectiveness-of-nivolumab-in-patients-with-advanced-renal-cell-carcinoma-treated-in-the-united-states
#1
Charles McCrea, Sukhvinder Johal, Shuo Yang, Justin Doan
Background: We evaluated the cost-effectiveness of nivolumab versus everolimus in patients with advanced renal cell carcinoma (RCC) from a US payer perspective. Methods: A partitioned survival model consisting of three health states, progression-free survival (PFS), progressive disease, and death, was developed to evaluate the cost-effectiveness of intravenous nivolumab versus oral everolimus over a lifetime. The proportion of patients in each state was calculated based on parametric distributions fitted to PFS and overall survival (OS) data from CheckMate 025 (N = 821), a large randomized phase 3 trial of nivolumab versus everolimus for advanced RCC...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29456111/methyllucidone-inhibits-stat3-activity-by-regulating-the-expression-of-the-protein-tyrosine-phosphatase-meg2-in-du145-prostate-carcinoma-cells
#2
Yena Jin, Young Hwan Kim, Jin Yong Park, Yu-Jin Lee, Hyun-Mi Oh, Sung-Kyu Choi, Dong Cho Han, Byoung-Mog Kwon
During the search for signal transducer and activator of transcription 3 (STAT3) inhibitors from natural products, methyllucidone, isolated from Lindera species (Lauraceae), was identified as a STAT3 inhibitor. Methyllucidone inhibited STAT3 phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU145 prostate cancer cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr-705 in LNCaP cells. Methyllucidone decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, Bcl-2, Mcl-1, and survivin...
February 8, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29454306/record-4-multicenter-phase-2-trial-of-second-line-everolimus-in-patients-with-metastatic-renal-cell-carcinoma-asian-versus-non-asian-population-subanalysis
#3
Lin Yang, Anna Alyasova, Dingwei Ye, Antonia Ridolfi, Luca Dezzani, Robert J Motzer
BACKGROUND: RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients...
February 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29453759/systemic-treatment-of-patients-with-advanced-unresectable-hepatocellular-carcinoma-emergence-of-therapies
#4
REVIEW
Weijing Sun, Roniel Cabrera
To date, sorafenib, a multiple tyrosine kinase inhibitor, is the only systemic agent approved by the FDA in the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). Several other tyrosine kinase-inhibiting agents have been investigated in the first-line setting, either alone (sunitinib, brivanib, linifanib, and lenvatinib) or in combination with sorafenib (erlotinib and doxorubicin) in phase 3 trials. However, none of these studies demonstrated an improvement in survival over sorafenib...
February 17, 2018: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/29453627/a-phase-i-and-pharmacokinetic-study-of-taladegib-a-smoothened-inhibitor-in-japanese-patients-with-advanced-solid-tumors
#5
Hideki Ueno, Shunsuke Kondo, Shusuke Yoshikawa, Koichi Inoue, Valérie Andre, Masaomi Tajimi, Haruyasu Murakami
Background This phase I dose-escalation study investigated the safety of the Smoothened inhibitor taladegib in Japanese patients with advanced solid tumors. Methods Patients received taladegib orally once daily for 28-day cycles, using a 3 + 3 dose-escalation method. The primary objective was the safety and tolerability of taladegib at doses up to the global recommended dose (400 mg). Secondary objectives included pharmacokinetics, changes in skin glioma-associated oncogene homolog 1 (Gli1) transcript levels, and antitumor activity...
February 17, 2018: Investigational New Drugs
https://www.readbyqxmd.com/read/29452770/single-arm-phase-2-trial-of-elective-nodal-dose-reduction-for-patients-with-locoregionally-advanced-squamous-cell-carcinoma-of-the-head-and-neck
#6
Patrick D Maguire, Charles R Neal, Stuart M Hardy, Andrew M Schreiber
PURPOSE: To evaluate a novel chemoradiation therapy (CRT) regimen for patients with squamous cell carcinoma of the head and neck (SCCHN) incorporating a lower intensity modulated radiation therapy dose to electively treated neck lymph nodes than is currently standard. METHODS AND MATERIALS: Eligible patients had locally advanced SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx. The 7-week CRT course consisted of weekly cisplatin at 35 mg/m 2 concurrently with sequential-boost intensity modulated radiation therapy: 36 Gy to high- and low-risk planning target volumes followed by a sequential boost to the high-risk planning target volume to 70 Gy...
December 28, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29444544/uridine-5-diphospho-glucuronosyltransferase-1a-expression-as-an-independent-prognosticator-in-urothelial-carcinoma-of-the-upper-urinary-tract
#7
Koji Izumi, Satoshi Inoue, Hiroki Ide, Kazutoshi Fujita, Taichi Mizushima, Guiyang Jiang, Seiji Yamaguchi, Hiroaki Fushimi, Norio Nonomura, Hiroshi Miyamoto
OBJECTIVE: To determine the expression status of uridine 5'diphospho-glucuronosyltransferase 1A, a major phase II drug metabolism enzyme, in upper urinary tract urothelial carcinoma, as well as to assess its prognostic significance. METHODS: We immunohistochemically stained for uridine 5'diphospho-glucuronosyltransferase 1A in tissue microarray consisting of 99 upper urinary tract urothelial carcinoma samples and paired non-neoplastic urothelial tissues. We also assessed the effect of uridine 5'diphospho-glucuronosyltransferase 1A knockdown on urothelial cancer cell growth...
February 14, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29440068/molecular-characterization-of-renal-cell-carcinoma-a-potential-three-microrna-prognostic-signature
#8
Soum D Lokeshwar, Asif Talukder, Travis J Yates, Martin J P Hennig, Michael Garcia-Roig, Sarrah S Lahorewala, Naureen N Mullani, Zachary Klaassen, Bruce R Kava, Murugesan Manoharan, Mark S Soloway, Vinata Lokeshwar
BACKGROUND: Aberrantly expressed microRNAs (miR) promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify a miRNA signature for predicting clinical outcome in RCC patients we used a four-pronged interconnected approach. METHODS: Differentially expressed miRs were identified and analyzed in 113 specimens (Normal kidney: 59; tumor: 54)...
February 12, 2018: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/29439857/axitinib-in-combination-with-pembrolizumab-in-patients-with-advanced-renal-cell-cancer-a-non-randomised-open-label-dose-finding-and-dose-expansion-phase-1b-trial
#9
Michael B Atkins, Elizabeth R Plimack, Igor Puzanov, Mayer N Fishman, David F McDermott, Daniel C Cho, Ulka Vaishampayan, Saby George, Thomas E Olencki, Jamal C Tarazi, Brad Rosbrook, Kathrine C Fernandez, Mariajose Lechuga, Toni K Choueiri
BACKGROUND: Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. METHODS: In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma...
February 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29436682/fatostatin-suppresses-growth-and-enhances-apoptosis-by-blocking-srebp-regulated-metabolic-pathways-in-endometrial-carcinoma
#10
Shuhong Gao, Zhengzheng Shi, Xin Li, Wenzhi Li, Yiling Wang, Zhiming Liu, Jie Jiang
Fatostatin, a chemical inhibitor of the sterol regulatory element‑binding protein (SREBP) pathway, has been reported to possess high antitumor activity against prostate and pancreatic cancer. The main aim of the present study was to investigate the effects and mechanism of fatostatin in endometrial carcinoma (EC). In the present study, we determined that fatostatin inhibited EC cell viability and colony formation capacity, decreased the invasive and migratory capacities of EC cells, induced EC cell cycle arrest at the G2/M phase and stimulated caspase‑mediated apoptosis of EC cells...
February 13, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29435872/a-phase-ii-trial-of-concurrent-chemoradiotherapy-with-weekly-paclitaxel-and-carboplatin-in-advanced-oesophageal-carcinoma
#11
Kuai-Le Zhao, Yi Xia, Yun-Hai Li, Yun Chen, Qi Liu, Jun-Hua Zhang, Jia-Ying Deng, Ta-Shan Ai, Han-Ting Zhu, Harun Badakhshi
BACKGROUND: This study was performed to assess the efficacy and feasibility of definitive chemoradiotherapy consisting of weekly doses of combined paclitaxel and carboplatin concurrent with radiation therapy, followed by 2 cycles of consolidation chemotherapy for advanced esophageal carcinoma. METHODS: Eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; and adequate organ function...
February 12, 2018: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29434984/antitumor-effect-of-membrane-type-tim-3-on-hepatocellular-carcinoma-hepa1-6-cells-of-icr-mice
#12
Ju Liu, Haiying Sun, Dan Shen, Mingmin Wang, Zirong Wen
In the present study, the inhibitory effect of transmembrane Tim-3 on hepatocellular carcinoma Hepa1-6 cells and the potential application of Tim-3 on immune system of Institute of Cancer Research (ICR) mice loaded with Hepa1-6 hepatocellular carcinoma was investigated. The animal model was established via inoculation of Hepa1-6 hepatocarcinoma cells at the hind thigh of ICR mice. Recombinant vector plasmids were transfected at the same site for gene therapy by injection to observe the inhibitory effect of Tim-3 on tumor growth...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434911/novel-betulin-derivative-induces-anti-proliferative-activity-by-g2-m-phase-cell-cycle-arrest-and-apoptosis-in-huh7-cells
#13
Zhen-Jian Zhuo, Min-Jie Xiao, Hui-Ran Lin, Jing Luo, Tao Wang
Betulin (BT) has been identified to exhibit potential benefits for treating hepatocellular carcinoma (HCC). The results of the present study demonstrated that a new semisynthetic derivative of BT, 3,28-di-(2-nitroxy-acetyl)-oxy-BT, may effectively decrease the viability of Huh7 cells. Mechanistic studies revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT inhibited the transition between G2 and M phase of the cell cycle by regulating cell cycle regulatory proteins. Additional study revealed that 3,28-di-(2-nitroxy-acetyl)-oxy-BT may trigger Huh7 cells to undergo caspase-dependent apoptosis as an increased proportion of cells were identified in the sub-G1 phase, which may be a result of poly(ADP-ribose) polymerase cleavage and caspase activation...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434733/shikonin-causes-apoptosis-by-disrupting-intracellular-calcium-homeostasis-and-mitochondrial-function-in-human-hepatoma-cells
#14
Hui Wang, Zheng Liu, Xiangchen Li, Ruijie Zhao, Yabin Pu, Handong Wu, Weijun Guan
Shikonin is known to suppress proliferation and induce apoptosis in a variety of cancer cell lines. In the present study, SMMC-7721 human hepatocellular carcinoma cells were treated with shikonin (1, 2 or 4 µM) for 12-48 h. Cell morphological alterations and DNA damage were determined. Furthermore, changes in cell cycle, mitochondrial transmembrane potential, calcium homeostasis and levels of reactive oxygen species were measured. Shikonin-treated SMMC-7721 cells exhibited morphological changes and DNA damage...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434680/predictors-of-anti-vegf-drug-induced-hypertension-using-different-hypertension-criteria-a-secondary-analysis-of-the-comparz-study
#15
Arduino A Mangoni, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich
Background: There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria. Methods: We assessed the associations between clinical and demographic factors (n = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations versus baseline, in a post hoc analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study)...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29433902/safety-and-efficacy-of-pd-1-pd-l1-inhibitors-in-treatment-naive-and-chemotherapy-refractory-patients-with-non-small-cell-lung-cancer-a-systematic-review-and-meta-analysis
#16
Monica Khunger, Prantesh Jain, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors...
January 10, 2018: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29433850/lenvatinib-versus-sorafenib-in-first-line-treatment-of-patients-with-unresectable-hepatocellular-carcinoma-a-randomised-phase-3-non-inferiority-trial
#17
Masatoshi Kudo, Richard S Finn, Shukui Qin, Kwang-Hyub Han, Kenji Ikeda, Fabio Piscaglia, Ari Baron, Joong-Won Park, Guohong Han, Jacek Jassem, Jean Frederic Blanc, Arndt Vogel, Dmitry Komov, T R Jeffry Evans, Carlos Lopez, Corina Dutcus, Matthew Guo, Kenichi Saito, Silvija Kraljevic, Toshiyuki Tamai, Min Ren, Ann-Lii Cheng
BACKGROUND: In a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma. METHODS: This was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions...
February 9, 2018: Lancet
https://www.readbyqxmd.com/read/29433670/genistein-induced-anticancer-effects-on-pancreatic-cancer-cell-lines-involves-mitochondrial-apoptosis-g-0-g-1-cell-cycle-arrest-and-regulation-of-stat3-signalling-pathway
#18
Yi-Liang Bi, Min Min, Wei Shen, Yan Liu
BACKGROUND: Genistein is a natural flavonoid that has been reported to exhibit anticancer effects against different types of cancers which include, but are not limited to, breast and oral squamous cell carcinoma. PURPOSE: The present study was designed to evaluate the anticancer effects of the natural flavonoid genistein against pancreatic cancer cell lines and to explore the underlying mechanism. METHODS: Antiproliferative activity was investigated by MTT assay...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29432993/oridonin-inhibits-oral-cancer-growth-and-pi3k-akt-signaling-pathway
#19
Jing Yang, Xianyue Ren, Liping Zhang, Yuanyuan Li, Bin Cheng, Juan Xia
Oridonin, a bioactive diterpenoid purified from Rabdosia rubescens, has been shown to possess anticancer capacity in several cancer types. However, its effects on oral squamous cell carcinoma (OSCC) cells remain unclear. This study aimed to investigate the anticancer ability of oridonin in OSCC cells, including proliferation, apoptosis and underlying mechanisms using the OSCC cell lines, UM1 and SCC25. The results showed that oridonin not only inhibited proliferation and clonal formation but also induced G2/M cell cycle arrest and apoptosis in UM1 and SCC25 cells in a dose-dependent manner...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29432567/bile-acid-sequestration-by-cholestyramine-mitigates-fgfr4-inhibition-induced-alt-elevation
#20
Heiko S Schadt, Armin Wolf, Joerg Andreas Mahl, Kuno Wuersch, Philippe Couttet, Marianne Schwald, Audrey Fischer, Mathilde Lienard, Corinne Emotte, Chi-Hse Teng, Elizabeth Skuba, Terrilyn A Richardson, Luigi Manenti, Andreas Weiss, Diana Graus Porta, Robin A Fairhurst, Gerd A Kullak-Ublick, Salah-Dine Chibout, Francois Pognan, William Kluwe, Jacqueline Kinyamu-Akunda
The FGF19-FGFR4-βKlotho (KLB) pathway plays an important role in the regulation of bile acid (BA) homeostasis. Aberrant activation of this pathway has been described in the development and progression of a subset of liver cancers including hepatocellular carcinoma (HCC), establishing FGFR4 as an attractive therapeutic target for such solid tumors. FGF401 is a highly selective FGFR4 kinase inhibitor being developed for HCC, currently in Phase I/II clinical studies. In preclinical studies in mice and dogs, oral administration of FGF401 led to induction of Cyp7a1, elevation of its peripheral marker 7alpha-hydroxy-4-cholesten-3-one (C4), increased BA pool size, decreased serum cholesterol and diarrhea in dogs...
February 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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