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https://www.readbyqxmd.com/read/28434191/the-effect-of-parotid-gland-sparing-imrt-on-salivary-composition-flow-rate-and-xerostomia-measures
#1
Thomas M Richards, Tara Hurley, Lorna Grove, Kevin J Harrington, Guy H Carpenter, Gordon B Proctor, Christopher M Nutting
OBJECTIVES: To describe parotid gland (PG) saliva organic and inorganic composition and flow rate changes, after curative intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC) and analyse the relationship between PG saliva analytes and xerostomia measures. METHODS AND MATERIALS: Twenty-six patients recruited to five prospective phase 2 or 3 trials which assessed toxicity and efficacy of IMRT by HNC subsite, provided longitudinal PG salivas. Salivary flow rate, subjective and objective xerostomia measures were prospectively collected and salivas tested for inorganic and organic analytes...
April 23, 2017: Oral Diseases
https://www.readbyqxmd.com/read/28433806/polymorphism-of-cyp1a1-gene-variants-rs4646903-and-rs1048943-relation-to-the-incidence-of-cervical-cancer-in-chhattisgarh
#2
Vijaylakshmi Jain, Yashwant K Ratre, Dnyanesh Amle, Pankaj K Mishra, Pradeep K Patra
Cytochrome P450 CYP1A1 is a phase 1 xenobiotic metabolizing enzyme involved in the metabolism of toxins, endogenous hormones and pharmaceutical drugs. It is therefore possible that polymorphism of CYP1A1 gene producing functional changes in the enzyme may be susceptible factors in cervical carcinogenesis. This study was aimed to look association of CYP1A1m1 (T>C) and m2 (A>G) gene polymorphisms in Chhattisgarh population. In this case-control study, we analyzed leukocyte DNA from a total of 200 subjects form Chhattisgarh (100 cases and 100 controls)...
April 13, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28432610/left-versus-right-does-location-matter-for-refractory-metastatic-colorectal-cancer-patients-in-phase-1-clinical-trials
#3
Sukeshi Patel Arora, Norma S Ketchum, Joel Michalek, Jonathon Gelfond, Devalingam Mahalingam
PURPOSE: Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. METHODS: A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012...
April 22, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28432176/a-phase-i-study-of-the-cdk4-6-inhibitor-ribociclib-lee011-in-pediatric-patients-with-malignant-rhabdoid-tumors-neuroblastoma-and-other-solid-tumors
#4
Birgit Geoerger, Franck Bourdeaut, Steven G DuBois, Matthias Fischer, James I Geller, Nicholas G Gottardo, Aurélien Marabelle, Andrew D J Pearson, Shakeel Modak, Thomas Cash, Giles W Robinson, Marlyane Motta, Alessandro Matano, Suraj G Bhansali, Jason R Dobson, Sudha Parasuraman, Susan N Chi
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off)...
April 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28431881/design-and-synthesis-of-1-2-3-triazolo-phenanthrene-hybrids-as-cytotoxic-agents
#5
Niggula Praveen Kumar, Shalini Nekkanti, S Sujana Kumari, Pankaj Sharma, Nagula Shankaraiah
A series of new 1,2,3-triazolo-phenanthrene hybrids has been synthesized by employing Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were evaluated for their in vitro cytotoxic potential against various human cancer cell lines viz. lung (A549), prostate (PC-3 and DU145), gastric (HGC-27), cervical (HeLa), triple negative breast (MDA-MB-231, MDA-MB-453) and breast (BT-549, 4T1) cells. Among the tested compounds, 7d displayed highest cytotoxicity against DU145 cells with IC50 value of 1...
April 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28431878/design-synthesis-and-anticancer-activity-of-novel-nopinone-based-thiosemicarbazone-derivatives
#6
Yunyun Wang, Wen Gu, Yu Shan, Fei Liu, Xu Xu, Yiqin Yang, Qiangjian Zhang, Yan Zhang, Hongbo Kuang, Zhonglong Wang, Shifa Wang
A series of new nopinone-based thiosemicarbazone derivatives were designed and synthesized as potent anticancer agents. All these compounds were identified by (1)H NMR, (13)C NMR, HR-MS spectra analyses. In the in vitro anticancer activity, most derivatives showed considerable cytotoxic activity against three human cancer cell lines (MDA-MB-231, SMMC-7721 and Hela). Among them, compound 4i exhibited most potent antitumor activity against three cancer cell lines with the IC50 values of 2.79±0.38, 2.64±0.17 and 3...
April 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28430579/antiangiogenesis-and-gene-aberration-related-therapy-may-improve-overall-survival-in-patients-with-concurrent-kras-and-tp53-hotspot-mutant-cancer
#7
Zhijie Wang, Sarina Piha-Paul, Filip Janku, Vivek Subbiah, Naiyi Shi, Jing Gong, Chetna Wathoo, Kenna Shaw, Kenneth Hess, Russell Broaddus, Aung Naing, David Hong, Apostolia M Tsimberidou, Daniel Karp, James Yao, Funda Meric-Bernstam, Siqing Fu
PURPOSE: Genetic alterations such as activating KRAS and/or inactivating TP53 are thought to be the most common drivers to tumorigenesis. Therefore, we assessed phase I cancer patients with KRAS+/TP53+ mutations. RESULTS: Approximately 8% of patients referred to phase I clinical trials harbored concurrent KRAS and TP53 mutations. Patients who received a phase I trial therapy (n = 57) had a median OS of 12 months, compared with 4.6 months in those who were not treated (n = 106; p = 0...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429140/a-phase-i-ii-study-on-stereotactic-body-radiotherapy-with-real-time-tumor-tracking-using-cyberknife-based-on-the-monte-carlo-algorithm-for-lung-tumors
#8
Hiromitsu Iwata, Satoshi Ishikura, Taro Murai, Michio Iwabuchi, Mitsuhiro Inoue, Koshi Tatewaki, Seiji Ohta, Naoki Yokota, Yuta Shibamoto
BACKGROUND: In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. METHODS: Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT...
April 20, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#9
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428286/a-genetic-analysis-of-the-caenorhabditis-elegans-detoxification-response
#10
Tetsunari Fukushige, Harold E Smith, Johji Miwa, Michael W Krause, John A Hanover
Oxidative damage contributes to human diseases of aging including diabetes, cancer, and cardiovascular disorders. Reactive oxygen species resulting from xenobiotic and endogenous metabolites are sensed by a poorly understood process, triggering a cascade of regulatory factors and leading to the activation of the transcription factor Nrf2 (SKN-1 in Caenorhabditis elegans). Nrf2/SKN-1 activation promotes the induction of the Phase II detoxification system that serves to limit oxidative stress. We have extended a previous C...
April 19, 2017: Genetics
https://www.readbyqxmd.com/read/28427507/is-still-there-a-place-for-orteronel-in-management-of-prostate-cancer-data-from-a-literature-based-meta-analysis-of-randomized-trials
#11
REVIEW
Giandomenico Roviello, Chiara Pacifico, Giorgio Chiriacò, Daniele Generali
Orteronel (TAK-700) is an oral, non-steroidal 17,20-lyase inhibitor with higher specificity for 17,20 lyase over 17 hydroxylase. The first phase III studies showed an advantage with orteronel compared with placebo in terms of progression free survival and response of PSA. Unfortunately orteronel did not significantly prolong the overall survival. In order to assess the efficacy of orteronel in prostate cancer, we evaluated all available data on orteronel in the management of prostate cancer. A total of 2716 patients were evaluated from 3 randomized trials...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427160/biomarker-analysis-of-the-phase-3-torch-trial-for-first-line-erlotinib-versus-chemotherapy-in-advanced-non-small-cell-lung-cancer-patients
#12
Lucia Kim, Mauro Saieg, Massimo Di Maio, Ciro Gallo, Charles Butts, Fortunato Ciardiello, Ronald Feld, Dengxiao Cheng, Vittorio Gebbia, Marco Angelo Burgio, Yasmin Alam, Simona Signoriello, Antonio Rossi, Natasha Leighl, Paolo Maione, Alessandro Morabito, Geoffrey Liu, Ming-Sound Tsao, Francesco Perrone, Cesare Gridelli
BACKGROUND: The TORCH phase III trial compared the efficacy of first-line erlotinib followed by chemotherapy at progression (experimental arm) with the reverse sequence (standard arm) in unselected advanced non-small cell lung cancer (NSCLC) patients. Here we report biomarker analyses. METHODS: EGFR and KRAS mutation, expression of EGFR family members and of cMET and PTEN and EGFR and ABCG2 germline polymorphisms were tested on tumor tissue or blood samples to either confirm previously proposed predictive role or describe it in an explorative setting...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427036/the-dose-dependent-effect-of-zearalenone-on-mitochondrial-metabolism-plasma-membrane-permeabilization-and-cell-cycle-in-human-prostate-cancer-cell-lines
#13
Karolina Kowalska, Dominika Ewa Habrowska-Górczyńska, Kamila Domińska, Agnieszka Wanda Piastowska-Ciesielska
Zearalenone (ZEA) is a nonsteroidal mycotoxin produced by several fungi of the genus Fusarium spp. It is known to play various roles in the regulation of the prostate cancer cell cycle, including carcinogenesis. The present study evaluates the influence of ZEA on the mitochondrial metabolism, plasma membrane permeabilization and cell cycle of prostate cancer cells. At concentrations of 100 nM and 0.3 nM, ZEA caused a decrease in the oxidative activity of mitochondria, as well as increases in LDH release, apoptosis induction and the number of cells in the G0/G1 phase...
April 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28426267/a-phase-2-trial-of-single-agent-axitinib-as-maintenance-therapy-following-first-line-treatment-with-modified-folfox-bevacizumab-in-patients-with-metastatic-colorectal-cancer
#14
Johanna C Bendell, Mathew Joseph, Kirk Barnes, Mark Mainwaring, Dianna Shipley, Chandra Reddy, Laura Blakely, Ronald Blachly, Cassie M Lane, Chris Earwood, Michel Kuzur
This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for patients with metastatic colorectal cancer (mCRC) following first-line treatment with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed by axitinib maintenance after four cycles. The primary endpoint was progression-free survival (PFS). Seventy patients were enrolled. Common treatment-related toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral neuropathy during axitinib treatment...
April 20, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28426104/a-randomized-open-label-phase-iii-trial-comparing-amrubicin-versus-docetaxel-in-patients-with-previously-treated-non-small-cell-lung-cancer
#15
H Yoshioka, N Katakami, H Okamoto, Y Iwamoto, T Seto, T Takahashi, N Sunaga, S Kudoh, K Chikamori, M Harada, H Tanaka, H Saito, H Saka, K Takeda, N Nogami, N Masuda, T Harada, H Kitagawa, H Horio, T Yamanaka, M Fukuoka, N Yamamoto, K Nakagawa
Background: Amrubicin is approved for treating non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no direct comparisons between amrubicin and docetaxel, a standard treatment for NSCLC, have been reported. Patients and methods: We conducted a randomized phase III trial of Japanese NSCLC patients after one or two chemotherapy regimens. Patients were randomized to amrubicin (35 mg/m2 on days 1-3 every 3 weeks) or docetaxel (60 mg/m2 on day 1 every 3 weeks)...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28426102/infection-related-complications-during-treatment-for-childhood-acute-lymphoblastic-leukemia
#16
H Inaba, D Pei, J Wolf, S C Howard, R T Hayden, M Go, O Varechtchouk, T Hahn, J Buaboonnam, M L Metzger, J E Rubnitz, R C Ribeiro, J T Sandlund, S Jeha, C Cheng, W E Evans, M V Relling, C-H Pui
Background: Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking. Patients and methods: We evaluated infection-related complications that were grade ≥3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period. Results: Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively...
February 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28425574/factors-associated-with-sustainability-of-2-quality-improvement-programs-after-achieving-early-implementation-success-a-qualitative-case-study
#17
Stephanie M C Ament, Freek Gillissen, Albine Moser, José M C Maessen, Carmen D Dirksen, Maarten F von Meyenfeldt, Trudy van der Weijden
RATIONALE, AIMS, AND OBJECTIVES: Sustainability of innovations is a relatively new concept in health care research and has become an issue of growing interest. The current study explored factors related to the sustainability of 2 multidisciplinary hospital-based programs 3 to 6 years after achieving early implementation success. METHOD: An exploratory qualitative study was conducted into 2 implementation cases, an Enhanced Recovery After Surgery program for colorectal surgery and a short-stay program for breast cancer surgery...
April 20, 2017: Journal of Evaluation in Clinical Practice
https://www.readbyqxmd.com/read/28425345/surrogate-marker-analysis-in-cancer-clinical-trials-through-time-to-event-mediation-techniques
#18
Sjouke Vandenberghe, Luc Duchateau, Leen Slaets, Jan Bogaerts, Stijn Vansteelandt
The meta-analytic approach is the gold standard for validation of surrogate markers, but has the drawback of requiring data from several trials. We refine modern mediation analysis techniques for time-to-event endpoints and apply them to investigate whether pathological complete response can be used as a surrogate marker for disease-free survival in the EORTC 10994/BIG 1-00 randomised phase 3 trial in which locally advanced breast cancer patients were randomised to either taxane or anthracycline based neoadjuvant chemotherapy...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/28425029/comparison-of-a-novel-formulation-of-abiraterone-acetate-vs-the-originator-formulation-in-healthy-male-subjects-two-randomized-open-label-crossover-studies
#19
Ronald Goldwater, Azra Hussaini, Bill Bosch, Paul Nemeth
BACKGROUND AND OBJECTIVE: Abiraterone acetate is approved for the treatment of metastatic castration-resistant prostate cancer. The originator abiraterone acetate (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure. Abiraterone acetate fine particle (AAFP) is a proprietary formulation (using SoluMatrix Fine Particle Technology™) designed to increase the oral bioavailability of abiraterone acetate. Here, we report on two phase I studies in healthy male subjects aged 18-50 years...
April 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28424962/phase-i-dose-escalation-study-of-milciclib-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#20
Sandrine Aspeslagh, Kunwar Shailubhai, Rastilav Bahleda, Anas Gazzah, Andréa Varga, Antoine Hollebecque, Christophe Massard, Anna Spreafico, Michele Reni, Jean-Charles Soria
BACKGROUND: This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m(2)/day, n = 3; 60 mg/m(2)/day, n = 3; and 80 mg/m(2)/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m(2)/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle...
April 19, 2017: Cancer Chemotherapy and Pharmacology
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