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Response evaluation of solid tumors

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https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#1
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28645941/a-first-time-in-human-study-of-gsk2636771-a-phosphoinositide-3-kinase-beta-selective-inhibitor-in-patients-with-advanced-solid-tumors
#2
Joaquin Mateo, Gopinath Ganji, Charlotte Lemech, Howard A Burris, Sae-Won Han, Karen E Swales, Shaun Decordova, Maurice P DeYoung, Deborah A Smith, Shanker Kalyana-Sundaram, Jiuhua Wu, Monica Motwani, Rakesh Kumar, Jerry M Tolson, Sun Young Rha, Hyun Cheol Chung, Joseph Paul Eder, Sunil Sharma, Yung-Jue Bang, Jeffrey R Infante, Li Yan, Johann S de Bono, Hendrik-Tobias Arkenau
The phosphoinositide 3 kinase (PI3K)/protein kinase B (AKT) pathway is commonly activated in several tumor types. Selective targeting of p110β could result in successful pathway inhibition while avoiding the on and off target effects of pan-PI3K inhibitors. GSK2636771 is a potent, orally bioavailable, adenosine triphosphate-competitive, selective inhibitor of PI3Kβ.<br /><br />Experimental Design: <p>We evaluated the safety, pharmacokinetics, pharmacodynamics and antitumor activity of GSK2636771 to define the recommended Phase II dose (RP2D)...
June 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#3
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#4
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635404/safety-and-efficacy-of-hepasphere-50-100%C3%A2-%C3%AE-m-in-the-treatment-of-hepatocellular-carcinoma
#5
Charles Edouard Zurstrassen, Luiz Paulo De Oliveira Gireli, Chiang Jeng Tyng, Almir Galvão Vieira Bitencourt, Marcos Duarte Guimarães, Paula Nicole Vieira Barbosa, Aline Cristine Barbosa Santos Cavalcante, João Paulo Matushita Junior, Mauricio Kauark Amoedo, Felipe Jose Coimbra, Rogério Camargo Pinheiro Alves, Rubens Chojniak
AIM: To evaluate the effects of HepaSphere 50-100 μm (Merit Medical) as a doxorubicin carrier and embolization agent for the treatment of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A prospective analysis of 18 patients recruited from a national cancer center was conducted. This analysis evaluated the efficacy and safety of HepaSphere, as expressed by the treatment response rate (measured by the modified Response Evaluation Criteria in Solid Tumors, mRECIST) and by the prevalence of treatment-related adverse events, respectively...
February 14, 2017: Minimally Invasive Therapy & Allied Technologies: MITAT
https://www.readbyqxmd.com/read/28634727/safety-and-efficacy-of-chemosaturation-in-patients-with-primary-and-secondary-liver-tumors
#6
Martha M Kirstein, Steffen Marquardt, Nils Jedicke, Silke Marhenke, Wolfgang Koppert, Michael P Manns, Frank Wacker, Arndt Vogel
BACKGROUND: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; hepatic CHEMOSAT(®) delivery system; Delcath Systems Inc, USA) is a novel medical device, which delivers high doses of melphalan directly to the liver in patients with primary and secondary liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. The aim of this study was to analyze the safety and efficacy of the second-generation CS-PHP after 54 treatments at Hannover Medical School, Germany...
June 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28634515/transarterial-chemoembolization-using-40-%C3%A2%C2%B5m-drug-eluting-beads-for-hepatocellular-carcinoma
#7
Giorgio Greco, Tommaso Cascella, Antonio Facciorusso, Roberto Nani, Rodolfo Lanocita, Carlo Morosi, Marta Vaiani, Giuseppina Calareso, Francesca G Greco, Antonio Ragnanese, Marco A Bongini, Alfonso V Marchianò, Vincenzo Mazzaferro, Carlo Spreafico
AIM: To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment. METHODS: Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging...
May 28, 2017: World Journal of Radiology
https://www.readbyqxmd.com/read/28634283/phase-ib-study-of-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-combination-with-pembrolizumab-mk-3475-in-patients-with-advanced-solid-tumors
#8
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28623430/a-phase-i-ii-study-of-suberoylanilide-hydroxamic-acid-saha-in-combination-with-trastuzumab-herceptin-in-patients-with-advanced-metastatic-and-or-local-chest-wall-recurrent-her2-amplified-breast-cancer-a-trial-of-the-ecog-acrin-cancer-research-group-e1104
#9
Lori J Goldstein, Fengmin Zhao, Molin Wang, Ramona F Swaby, Joseph A Sparano, Neal J Meropol, Kapil N Bhalla, Christine M Pellegrino, R Katherine Alpaugh, Carla I Falkson, Paula Klein, George W Sledge
PURPOSE: Suberoylanilide hydroxamic acid (SAHA; vorinostat), a small molecule inhibitor of histone deacetylase, attenuates signaling pathways known to confer trastuzumab resistance. A combination of SAHA and trastuzumab may be a promising strategy to improve the efficacy of trastuzumab against breast cancer. In this Phase I/II study, we evaluated the toxicity and response rate after treatment with SAHA and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with trastuzumab-resistant progressive disease...
June 16, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28623376/eanm-earl-harmonization-strategies-in-pet-quantification-from-daily-practice-to-multicentre-oncological-studies
#10
REVIEW
Nicolas Aide, Charline Lasnon, Patrick Veit-Haibach, Terez Sera, Bernhard Sattler, Ronald Boellaard
Quantitative positron emission tomography/computed tomography (PET/CT) can be used as diagnostic or prognostic tools (i.e. single measurement) or for therapy monitoring (i.e. longitudinal studies) in multicentre studies. Use of quantitative parameters, such as standardized uptake values (SUVs), metabolic active tumor volumes (MATVs) or total lesion glycolysis (TLG), in a multicenter setting requires that these parameters be comparable among patients and sites, regardless of the PET/CT system used. This review describes the motivations and the methodologies for quantitative PET/CT performance harmonization with emphasis on the EANM Research Ltd...
June 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28621686/pseudoprogression-in-microsatellite-instability-high-colorectal-cancer-during-treatment-with-combination-t-cell-mediated-immunotherapy-a-case-report-and-literature-review
#11
Young Kwang Chae, Si Wang, Halla Nimeiri, Aparna Kalyan, Francis J Giles
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28619042/metabolic-targeting-of-hif-dependent-glycolysis-reduces-lactate-increases-oxygen-consumption-and-enhances-response-to-high-dose-single-fraction-radiotherapy-in-hypoxic-solid-tumors
#12
Eric Leung, Rob A Cairns, Naz Chaudary, Ravi N Vellanki, Tuula Kalliomaki, Eduardo H Moriyama, Hilda Mujcic, Brian C Wilson, Bradly G Wouters, Richard Hill, Michael Milosevic
BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28614783/effectiveness-and-safety-of-pd-1-pd-l1-inhibitors-in-the-treatment-of-solid-tumors-a-systematic-review-and-meta-analysis
#13
REVIEW
Xiaohui Wang, Zhengqiang Bao, Xiaoju Zhang, Fei Li, Tianwen Lai, Chao Cao, Zhihua Chen, Wen Li, Huahao Shen, Songmin Ying
BACKGROUND: PD-1/PD-L1 inhibitors have been implicated as potentially effective anti-cancer therapies. Some clinical randomized controlled trials (RCTs) have been completed for a variety of PD-1/PD-L1 inhibitors to treat various malignancies, and more RCTs are still under way. We carried out this systematic meta-analysis to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors. METHODS: We searched PubMed, EMBASE, clinical trial registers, conference reports, and related reviews...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28612091/intracellular-vorinostat-accumulation-and-its-relationship-to-histone-deacetylase-activity-in-soft-tissue-sarcoma-patients
#14
Jürgen Burhenne, Lu Liu, Christoph E Heilig, Andreas D Meid, Margarete Leisen, Thomas Schmitt, Bernd Kasper, Walter E Haefeli, Gerd Mikus, Gerlinde Egerer
PURPOSE: In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects. METHODS: In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28609363/o6-methylguanine-dna-methyltransferase-status-does-not-predict-response-or-resistance-to-alkylating-agents-in-well-differentiated-pancreatic-neuroendocrine-tumors
#15
Nitya Raj, David S Klimstra, Natally Horvat, Liying Zhang, Joanne F Chou, Marinela Capanu, Olca Basturk, Richard Kinh Gian Do, Peter J Allen, Diane Reidy-Lagunes
OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing...
July 2017: Pancreas
https://www.readbyqxmd.com/read/28609226/phase-ii-trial-of-atezolizumab-as-first-line-or-subsequent-therapy-for-patients-with-programmed-death-ligand-1-selected-advanced-non-small-cell-lung-cancer-birch
#16
Solange Peters, Scott Gettinger, Melissa L Johnson, Pasi A Jänne, Marina C Garassino, Daniel Christoph, Chee Keong Toh, Naiyer A Rizvi, Jamie E Chaft, Enric Carcereny Costa, Jyoti D Patel, Laura Q M Chow, Marianna Koczywas, Cheryl Ho, Martin Früh, Michel van den Heuvel, Jeffrey Rothenstein, Martin Reck, Luis Paz-Ares, Frances A Shepherd, Takayasu Kurata, Zhengrong Li, Jiaheng Qiu, Marcin Kowanetz, Simonetta Mocci, Geetha Shankar, Alan Sandler, Enriqueta Felip
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled...
June 13, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28607134/dysfunctional-diversity-of-p53-proteins-in-adult-acute-myeloid-leukemia-projections-on-diagnostic-work-up-and-therapy
#17
Miron Prokocimer, Alina Molchadsky, Varda Rotter
The heterogeneous nature of Acute Myeloid Leukemia (AML) and its poor prognosis necessitate therapeutic improvement. Current advances in AML research yield important insights regarding AML genetic, epigenetic, evolutional, and clinical diversity, all in which dysfunctional p53 plays a key role. As p53 is central to hematopoietic stem cell functions, its aberrations affect AML evolution, biology and therapy response, and usually predict poor prognosis. While in human solid tumors TP53 is mutated in more than half of cases, TP53 mutations occur in less than a tenth of de-novo AML cases...
June 12, 2017: Blood
https://www.readbyqxmd.com/read/28602779/ceritinib-versus-chemotherapy-in-patients-with-alk-rearranged-non-small-cell-lung-cancer-previously-given-chemotherapy-and-crizotinib-ascend-5-a-randomised-controlled-open-label-phase-3-trial
#18
Alice T Shaw, Tae Min Kim, Lucio Crinò, Cesare Gridelli, Katsuyuki Kiura, Geoffrey Liu, Silvia Novello, Alessandra Bearz, Oliver Gautschi, Tony Mok, Makoto Nishio, Giorgio Scagliotti, David R Spigel, Stéphanie Deudon, Cheng Zheng, Serafino Pantano, Patrick Urban, Cristian Massacesi, Kalyanee Viraswami-Appanna, Enriqueta Felip
BACKGROUND: Ceritinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor, which has shown robust anti-tumour efficacy, along with intracranial activity, in patients with ALK-rearranged non-small-cell lung cancer. In phase 1 and 2 studies, ceritinib has been shown to be highly active in both ALK inhibitor-naive and ALK inhibitor-pretreated patients who had progressed after chemotherapy (mostly multiple lines). In this study, we compared the efficacy and safety of ceritinib versus single-agent chemotherapy in patients with advanced ALK-rearranged non-small-cell lung cancer who had previously progressed following crizotinib and platinum-based doublet chemotherapy...
June 8, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28601972/tak-228-formerly-mln0128-an-investigational-dual-torc1-2-inhibitor-plus-paclitaxel-with-without-trastuzumab-in-patients-with-advanced-solid-malignancies
#19
Howard A Burris, C D Kurkjian, L Hart, S Pant, P B Murphy, S F Jones, R Neuwirth, C G Patel, F Zohren, J R Infante
PURPOSE: This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. METHODS: Sixty-seven patients received TAK-228 6-40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m(2) (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20)...
June 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28600476/phase-ib-study-of-lumretuzumab-plus-cetuximab-or-erlotinib-in-solid-tumor-patients-and-evaluation-of-her3-and-heregulin-as-potential-biomarkers-of-clinical-activity
#20
Didier Meulendijks, Wolfgang Jacob, Emile E Voest, Morten Mau-Sørensen, Maria Martinez-Garcia, Alvaro Taus, Tania Fleitas, Andres Cervantes, Martijn Lolkema, Marlies Hg Langenberg, Maja J A de Jonge, Stefan Sleijfer, Ji-Youn Han, Antonio Calles, Enriqueta Felip, Sang-We Kim, Jan H M Schellens, Sabine Wilson, Marlene Thomas, Maurizio Ceppi, Georgina Meneses-Lorente, Ian James, Suzana Vega Harring, Rajiv Dua, Maitram Nguyen, Lori Steiner, Celine Adessi, Francesca Michielin, Birgit Bossenmaier, Martin Weisser, Ulrik Lassen
<br /> <p>This study investigated the safety, clinical activity and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.</p> <br />Experimental Design: <br /> <p>The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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