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Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

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https://www.readbyqxmd.com/read/30446590/neutrophil-extracellular-traps-induced-by-il-8-promote-diffuse-large-b-cell-lymphoma-progression-via-the-tlr9-signaling
#1
Man Nie, LinBin Yang, Xiwen Bi, Yu Wang, Peng Sun, Hang Yang, Panpan Liu, Zhiming Li, Yi Xia, Wenqi Jiang
PURPOSE: Over 30% of patients with diffuse large B cell lymphoma (DLBCL) experience treatment failure after first-line therapy. Neutrophil extracellular traps (NETs), a pathogen-trapping structure in tumor microenvironment, can promote the transition of autoimmunity to lymphomagenesis. Here, we investigate whether NETs play a novel role in DLBCL progression and its underlying mechanism. EXPERIMENTAL DESIGN: NETs in DLBCL tumor samples and plasma were detected by immunofluorescence and ELISA, respectively...
November 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30446589/-immunotherapy-for-glioblastoma-adoptive-t-cell-strategies
#2
Bryan D Choi, Marcela V Maus, Carl H June, John H Sampson
Glioblastoma (GBM) is a devastating disease with an extremely poor prognosis. Immune therapy via adoptive cell transfer (ACT), especially with T cells engineered to express chimeric antigen receptors (CARs), represents a particularly promising approach. Despite the recent success of CAR T cells for blood cancers, the question remains whether this powerful anti-cancer therapy will ultimately work for brain tumors, and if the primary immunologic challenges in this disease-which include antigenic heterogeneity, immune suppression and T-cell exhaustion-can be adequately addressed...
November 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30446588/predicting-treatment-response-based-on-rna-expression-in-large-datasets
#3
Aaron S Mansfield, Jin Jen
PD-L1 expression levels derived from >16,000 samples guided the selection of tumor types likely to benefit from pembrolizuamb monotherapy in clinical trials. While not fail-proof, FDA approvals for most of the prioritized indications speak to the power of RNA expression profiling and the value of large genomic datasets.
November 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30446587/inhibition-of-lef1-mediated-dclk1-by-niclosamide-attenuates-colorectal-cancer-stemness
#4
So-Yeon Park, Ji-Young Kim, Jang-Hyun Choi, Jee-Heun Kim, Choong-Jae Lee, Pomila Singh, Shubhashish Sarkar, Jeong-Heum Baek, Jeong-Seok Nam
PURPOSE: Niclosamide, an FDA-approved anthelmintic drug, has been characterized as a potent Wnt inhibitor that can suppress tumor growth and cancer stem-like cell (CSC) populations. However, the underlying molecular mechanisms remain poorly understood. The current study aimed to examine how Wnt inhibition by niclosamide preferentially targets CSCs. EXPERIMENTAL DESIGN: The mechanistic role of niclosamide in CSC inhibition was examined in public databases, human colorectal cancer (CRC) cells, CRC xenografts, and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC model...
November 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30442684/molecular-profiling-of-cohorts-of-tumor-samples-to-guide-clinical-development-of-pembrolizumab-as-monotherapy
#5
Mark Ayers, Michael Nebozhyn, Razvan Cristescu, Terrill K McClanahan, Rodolfo Perini, Eric Rubin, Jonathan D Cheng, David R Kaufman, Andrey Loboda
Purpose: Molecular profiling of large databases of human tumor gene expression profiles offers novel opportunities for informing decisions in clinical development programs. Experimental Design: Gene expression profile of programmed death ligand 1 (PD-L1) was explored in a dataset of 16,000 samples, including approximately 4,000 metastatic tumors, across >25 tumor types prevalent in the United States, looking for new indications for the programmed death 1 (PD-1) inhibitor pembrolizumab. PD-L1 expression was highly concordant with several genomic signatures indicative of immune-inflamed tumor microenvironment...
November 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30442683/-pik3ca-amplification-associates-with-aggressive-phenotype-but-not-markers-of-akt-mtor-signaling-in-endometrial-carcinoma
#6
Frederik Holst, Henrica M J Werner, Siv Mjøs, Erling A Hoivik, Kanthida Kusonmano, Elisabeth Wik, Anna Berg, Even Birkeland, William J Gibson, Mari K Halle, Jone Trovik, Andrew D Cherniack, Karl-Henning Kalland, Gordon B Mills, Christian F Singer, Camilla Krakstad, Rameen Beroukhim, Helga B Salvesen
Purpose: Amplification of PIK3CA , encoding the PI3K catalytic subunit alpha, is common in uterine corpus endometrial carcinoma (UCEC) and linked to an aggressive phenotype. However, it is unclear whether PIK3CA amplification acts via PI3K activation. We investigated the association between PIK3CA amplification, markers of PI3K activity, and prognosis in a large cohort of UCEC specimens. Experimental Design: UCECs from 591 clinically annotated patients including 83 tumors with matching metastasis ( n = 188) were analyzed by FISH to determine PIK3CA copy-number status...
November 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30442682/advances-in-her2-targeted-therapy-novel-agents-and-opportunities-beyond-breast-and-gastric-cancer
#7
Funda Meric-Bernstam, Amber Johnson, Ecaterina E Ileana Dumbrava, Kanwal Raghav, Kavitha Balaji, Michelle Bhatt, Rashmi K Murthy, Jordi Rodon, Sarina A Piha-Paul
The introduction of HER2-targeted therapy for breast and gastric patients with ERBB2(HER2) amplification/overexpression has led to dramatic improvements in oncologic outcomes. In the past 20 years, five HER2-targeted therapies have been FDA approved, four in the past 8 years. HER2-targeted therapy similarly was found to improve outcomes in HER2-positive gastric cancer. Over the past decade, with the introduction of next generation sequencing into clinical practice, our understanding of HER2 biology has dramatically improved...
November 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30429200/more-is-more-semi-annual-breast-mri-screening-in-brca1-mutation-carriers
#8
Christiane K Kuhl, Simone Schrading
Although annual MRI-screening has improved early diagnosis of hereditary breast-cancer, fast growth-rates of BRCA1-associated cancers can still lead to interval cancers, and/or node-positive disease. Using MRI with shorter screening intervals helps to effectively avoid both, interval cancers and node-positive stages, whereas there is no role for mammography in these women.
November 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30429199/inhibition-of-bub1-kinase-by-bay-1816032-sensitizes-tumor-cells-towards-taxanes-atr-and-parp-inhibitors-in-vitro-and-in-vivo
#9
Gerhard Siemeister, Anne Mengel, Amaury E Fernández-Montalván, Wilhelm Bone, Jens Schröder, Sabine Zitzmann-Kolbe, Hans Briem, Stefan Prechtl, Simon J Holton, Ursula Mönning, Oliver von Ahsen, Sandra Johanssen, Arwed Cleve, Vera Pütter, Marion Hitchcock, Franz von Nussbaum, Michael Brands, Karl Ziegelbauer, Dominik Mumberg
PURPOSE: The catalytic function of BUB1 is required for chromosome arm resolution and positioning of the chromosomal passenger complex for resolution of spindle attachment errors and plays only a minor role in spindle assembly checkpoint activation. Here we present the identification and preclinical pharmacological profile of the first BUB1 kinase inhibitor with good bioavailability. EXPERIMENTAL DESIGN: The Bayer compound library was screened for BUB1 kinase inhibitors and medicinal chemistry efforts to improve target affinity, physicochemical and pharmacokinetic parameters resulting in the identification of BAY 1816032 were performed...
November 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30429198/fli1-exonic-circular-rnas-as-a-novel-oncogenic-driver-to-promote-tumor-metastasis-in-small-cell-lung-cancer
#10
Lingyu Li, Wei Li, Naifei Chen, Haixin Zhao, Guang Xu, Yijing Zhao, Xin Pan, Xiaoying Zhang, Lei Zhou, Dehai Yu, Ailing Li, Jifan Hu, Jiuwei Cui
PURPOSE: The aberrantly upregulated Friend leukemia virus integration 1 ( FLI1 ) is closely correlated with the malignant phenotype of small cell lung cancer (SCLC). This study attempts to examine if FLI1 exonic circular RNAs (FECRs) function as a new malignant driver that determines the metastatic phenotype in SCLC. EXPERIMENTAL DESIGN: The expression of FECRs was examined in SCLC tissues and serum exosomes. The oncogenic activity of FECRs was investigated in SCLC cell lines and animal xenograft studies...
November 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30425093/rare-pathogenic-germline-variants-in-fanconi-anemia-genes-increase-risk-for-squamous-lung-cancer
#11
Myvizhi Esai Selvan, Robert J Klein, Zeynep H Gumus
PURPOSE: Lung cancer is the leading cause of cancer deaths worldwide, with substantial better prognosis in early stage as opposed to late state disease. Identifying genetic factors for lung squamous carcinoma (SqCC) risk will enable their use in risk stratification, and personalized intensive surveillance, early detection, and prevention strategies for high-risk individuals. EXPERIMENTAL DESIGN: We analyzed whole-exome sequencing datasets of 318 cases and 814 controls (discovery cohort) and then validated our findings in an independent cohort of 444 patients and 3,479 controls (validation cohort), all of European descent, totaling a combined cohort of 765 cases and 4,344 controls...
November 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30425092/preventing-lck-activation-in-car-t-cells-confers-treg-resistance-but-requires-4-1bb-signaling-for-them-to-persist-and-treat-solid-tumors-in-non-lymphodepleted-hosts
#12
Carter M Suryadevara, Rupen Desai, S Harrison Farber, Bryan D Choi, Adam M Swartz, Steven H Shen, Patrick C Gedeon, David J Snyder, James E Herndon, Patrick Healy, Elizabeth A Reap, Gary E Archer, Peter E Fecci, John H Sampson, Luis Sanchez-Perez
PURPOSE: CAR T cells have shown promise against solid tumors, but their efficacy has been limited, due in part, to immunosuppression by CD4+ FoxP3+ regulatory T cells (Tregs). Although lymphodepletion is commonly used to deplete Tregs, these regimens are non-specific, toxic, and provide only a narrow window before Tregs repopulate hosts. Importantly, CARs have also been shown to inadvertently potentiate Tregs by providing a source of IL-2 for Treg consumption. We explored whether disruption of the IL-2 axis would confer efficacy against solid tumors without the need for lymphodepletion...
November 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30425091/prognostic-value-of-rankl-opg-serum-levels-and-disseminated-tumor-cells-in-non-metastatic-breast-cancer
#13
Tilman D Rachner, Sabine Kasimir-Bauer, Andy Göbel, Kati Erdmann, Oliver Hoffmann, Andrew J Browne, Pauline Wimberger, Martina Rauner, Lorenz C Hofbauer, Rainer Kimmig, Ann-Kathrin Bittner
BACKGROUND: We assessed serum concentrations of the receptor activator of nuclear factor kappa-B ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), two proteins implicated in the development and progression of breast cancer (BC), in 509 patients with primary, non-metastatic BC. Then the results were evaluated with regards to the occurrence of bone metastases, the presence of disseminated tumor cells (DTC) in the bone marrow, survival and risk of developing metastatic disease...
November 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30425090/phase-1-study-of-amg-337-a-highly-selective-small-molecule-met-inhibitor-in-patients-with-advanced-solid-tumors
#14
David S Hong, Patricia M LoRusso, Omid Hamid, Filip Janku, Muaiad Kittaneh, Daniel V T Catenacci, Emily Chan, Tanios Bekaii-Saab, Shirish Gadgeel, Robert D Loberg, Benny M Amore, Yuying C Hwang, Rui Tang, Gataree Ngarmchamnanrith, Eunice L Kwak
PURPOSE: This first-in-human, open-label phase 1 study evaluated AMG 337, an oral, highly selective small-molecule inhibitor of MET in advanced solid tumors. EXPERIMENTAL DESIGN: Patients enrolled into dose-escalation cohorts received AMG 337 up to 400 mg once daily (QD) or up to 250 mg twice daily (BID), following a modified 3+3+3 design. Dose expansion was conducted in MET -amplified patients at the maximum tolerated dose (MTD). Primary endpoints included assessment of adverse events (AEs), establishment of the MTD, and pharmacokinetics; clinical response was a secondary endpoint...
November 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30420449/distinct-biological-types-of-ocular-adnexal-sebaceous-carcinoma-hpv-driven-and-virus-negative-tumors-arise-through-non-overlapping-molecular-genetic-alterations
#15
Michael T Tetzlaff, Jonathan L Curry, Jing Ning, Oded Sagiv, Thomas Kandl, Bo Peng, Diana Bell, Mark J Routbort, Courtney W Hudgens, Doina Ivan, TaeBeom Kim, Ken Chen, Agda Karina Eterovic, Kenna R Mills Shaw, Victor G Prieto, Anna Yemelyanova, Bita Esmaeli
PURPOSE: Ocular adnexal (OA) sebaceous carcinoma is an aggressive malignancy of the eyelid and ocular adnexa that frequently recurs and metastasizes, and effective therapies beyond surgical excision are lacking. There remains a critical need to define the molecular-genetic drivers of the disease to understand carcinomagenesis and progression and to devise novel treatment strategies. EXPERIMENTAL DESIGN: We present next generation sequencing of a targeted panel of cancer-associated genes in 42 and whole transcriptome RNA sequencing from 8 OA sebaceous carcinomas from 29 patients...
November 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30420448/e3611-a-randomized-phase-ii-study-of-ipilimumab-at-3-or-10-mg-kg-alone-or-in-combination-with-high-dose-interferon-%C3%AE-2b-in-advanced-melanoma
#16
Ahmad A Tarhini, Sandra J Lee, Xiaoxue Li, Uma N Rao, Arun Nagarajan, Mark R Albertini, Jerry W Mitchell, Stuart Wong, Mark A Taylor, Noel Laudi, Phu V Truong, Robert M Conry, John M Kirkwood
PURPOSE: Interferon-α favors a Th1 shift in immunity and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy supporting this hypothesis. EXPERIMENTAL DESIGN: E3611 followed a 2 by 2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipi doses) and (ii) ipi3 versus ipi10 (across HDI status)...
November 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30420447/preclinical-efficacy-of-endoglin-targeting-antibody-drug-conjugates-for-the-treatment-of-ewing-sarcoma
#17
Pilar Puerto-Camacho, Ana Teresa Amaral, Salah-Eddine Lamhamedi-Cherradi, Brian A Menegaz, Helena Castillo-Ecija, José Luis Ordóñez, Saioa Dominguez-Hormaetxe, Carmen Jordan-Perez, Juan Diaz-Martin, Laura Romero-Pérez, Maria Lopez-Alvarez, Gema Civantos-Jubera, María José Robles-Frias, Michele Biscuola, Cristina Ferrer, Jaume Mora, Branko Cuglievan, Keri L Schadler, Oliver Seifert, Roland E Kontermann, Klaus Pfizenmaier, Laureano Simon, Myriam Fabre, Angel M Carcaboso, Joseph A Ludwig, Enrique de Álava
PURPOSE: Endoglin (ENG; CD105) is a co-receptor of the transforming growth factor-β (TGF-β) family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGF-β, and as a soluble matricellular protein (sENG) when cleaved by matrix metalloproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma (ES), an aggressive bone cancer that primarily occurs in adolescents and young adults...
November 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30420446/targeting-purinergic-receptor-p2y2-prevents-the-growth-of-pancreatic-ductal-adenocarcinoma-by-inhibiting-cancer-cell-glycolysis
#18
Li-Peng Hu, Xiao-Xin Zhang, Shu-Heng Jiang, Ling-Ye Tao, Qing Li, Li-Li Zhu, Min-Wei Yang, Yan-Miao Huo, Yong-Sheng Jiang, Guang-Ang Tian, Xiao-Yan Cao, Yan-Li Zhang, Qin Yang, Xiao-Mei Yang, Ya-Hui Wang, Jun Li, Gary Guishan Xiao, Yong-Wei Sun, Zhi-Gang Zhang
PURPOSE: Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to prevent cancer progression. We aimed to determine whether blocking extracellular ATP-P2RY2 axis could be a potential therapeutic approach for PDAC treatment. EXPERIMENTAL DESIGN: Expression of P2RY2 was determined in 264 human PDAC samples, and correlated to patient survival...
November 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30420445/whole-body-imaging-of-cell-death-provides-a-systemic-minimally-invasive-dynamic-and-near-real-time-indicator-for-chemotherapeutic-drug-toxicity
#19
Steven E Johnson, Andrey Ugolkov, Chad R Haney, Gennadiy Bondarenko, Lin Li, Emily A Waters, Raymond Bergan, Andy Tran, Thomas V O'Halloran, Andrew P Mazar, Ming Zhao
PURPOSE: Response to toxicity in chemotherapies vary considerably from tissue to tissue and from patient to patient. An ability to monitor the tissue damage done by chemotherapy may have a profound impact on treatment and prognosis allowing for a proactive management in understanding and mitigating such events. For the first time, we investigated the feasibility of using whole-body imaging to map chemotherapeutic drug-induced toxicity on an individual-basis. EXPERIMENTAL DESIGN: In a preclinical proof-of-concept, rats were treated with a single clinical dose of cyclophosphamide, methotrexate or cisplatin...
November 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30420444/inhibition-of-mtor-signaling-and-clinical-activity-of-rapamycin-in-head-and-neck-cancer-in-a-window-of-opportunity-trial
#20
Terry A Day, Keisuke Shirai, Paul E O'Brien, Maria G Matheus, Kristina B Godwin, Amit J Sood, Anvesh Kompelli, Julie A Vick, Daniel Martin, Lynn A Vitale-Cross, Juan Luis Callejas-Varela, Zhiyong Wang, Xingyu Wu, Olivier Harismendy, Alfredo A Molinolo, Scott M Lippman, Carter Van Waes, Eva Szabo, J Silvio Gutkind
PURPOSE: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The goals were to evaluate the mTOR pathway as a therapeutic target for advanced HNSCC patients, and the clinical safety, anti-tumor, and molecular activity of rapamycin administration on HNSCC. EXPERIMENTAL DESIGN: Patients with untreated stage II-IVA HNSCC received rapamycin for 21 days (day 1, 15mg; days 2-12, 5mg) prior to definitive treatment with surgery or chemoradiation...
November 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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