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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/28939749/cd90-expression-controls-migration-and-predicts-dasatinib-response-in-glioblastoma
#1
Tony Avril, Amandine Etcheverry, Raphaël Pineau, Joanna Obacz, Gwénaële Jegou, Florence Jouan, Pierre-Jean Le Reste, Masumeh Hatami, Rivka R Colen, Brett L Carlson, Paul A Decker, Jann N Sarkaria, Elodie Vauléon, Dan Cristian Chiforeanu, Anne Clavreul, Jean Mosser, Eric Chevet, Véronique Quillien
PURPOSE: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells including glioblastoma (GBM) stem cells (GSCs). However, the molecular and cellular functions of CD90 remain unclear. EXPERIMENTAL DESIGN: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, GBM specimens' transcriptome associated with MRI features from GBM patients...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939748/in-depth-genetic-analysis-of-sclerosing-epithelioid-fibrosarcoma-reveals-recurrent-genomic-alterations-and-potential-treatment-targets
#2
Elsa Arbajian, Florian Puls, Cristina R Antonescu, M Fernanda Amary, Raf Sciot, Maria Debiec-Rychter, Vaiyapuri Sumathi, Marcus Järås, Linda Magnusson, Jenny Nilsson, Jakob Hofvander, Fredrik Mertens
PURPOSE: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid sarcoma (LGFMS). Some tumors display morphological characteristics of both SEF and LGFMS, so called hybrid SEF/LGFMS. Despite the overlap of gene fusion variants between these two tumor types, SEF is much more aggressive. The present study aimed to further characterize SEF and hybrid SEF/LGFMS genetically in order to better understand the role of the characteristic fusion genes and possible additional genetic alterations in tumorigenesis...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939747/a-pilot-trial-of-humanized-anti-gd2-monoclonal-antibody-hu14-18k322a-with-chemotherapy-and-natural-killer-cells-in-children-with-recurrent-refractory-neuroblastoma
#3
Sara M Federico, M Beth McCarville, Barry L Shulkin, Paul M Sondel, Jacquelyn A Hank, Paul Hutson, Michael Meagher, Aaron Shafer, Catherine Y Ng, Wing Leung, William E Janssen, Jianrong Wu, Shenghua Mao, Rachel C Brennan, Victor M Santana, Alberto Pappo, Wayne L Furman
PURPOSE: Anti-GD2 monoclonal antibodies (mAb), acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines and haploidentical natural killer (NK) cells. EXPERIMENTAL DESIGN: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40mg/m2/dose, days 2-5), GMCSF and IL-2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4) and ifosfamide/carboplatin/etoposide (courses 5,6)...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939746/phase-iii-clinical-trial-rerise-study-results-of-efficacy-and-safety-of-radotinib-compared-with-imatinib-in-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia
#4
Jae Yong Kwak, Sung-Hyun Kim, Suk Joong Oh, Dae Young Zang, Hawk Kim, Jeong-A Kim, Young Rok Do, Hyeoung-Joon Kim, Joon Seong Park, Chul Won Choi, Won-Sik Lee, Yeung-Chul Mun, Jee Hyun Kong, Joo-Seop Chung, Ho Jin Shin, Dae-Young Kim, Jinny Park, Chul Won Jung, Udomask Bunworasate, Narcisa Sonia Comia, Saengsuree Jootar, Harryanto Reksodiputro, Priscilla B Caguioa, Sung-Eun Lee, Dong-Wook Kim
PURPOSE: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for CML-CP in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. METHODS: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily (bid) radotinib doses, or imatinib daily (qd). The primary endpoint was major molecular response (MMR) by 12 months...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939745/a-novel-breast-cancer-index-for-prediction-of-distant-recurrence-in-hr-early-stage-breast-cancer-with-1-to-3-positive-nodes
#5
Yi Zhang, Brock E Schroeder, Piiha-Lotta Jerevall, Amy Ly, Hannah Nolan, Catherine A Schnabel, Dennis Sgroi
Study objective was to characterize the prognostic performance of a novel Breast Cancer Index model (BCIN+), an integration of BCI gene expression, tumor size, and grade, specifically developed for assessment of distant recurrence (DR) risk in HR+ breast cancer patients with 1-3 positive lymph nodes (pN1). <br><br> Experimental Design: Analysis was conducted in a well-annotated retrospective series of pN1 patients (N=402) treated with adjuvant endocrine therapy with or without chemotherapy using a pre-specified model...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939744/radiomics-analysis-for-evaluation-of-pathological-complete-response-to-neoadjuvant-chemoradiotherapy-in-locally-advanced-rectal-cancer
#6
Zhenyu Liu, Xiao-Yan Zhang, Yan-Jie Shi, Lin Wang, Hai-Tao Zhu, Zhen-Chao Tang, Shuo Wang, Xiao-Ting Li, Jie Tian, Ying-Shi Sun
PURPOSE: To develop and validate a radiomics model for evaluating pathological complete response (pCR) to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC). EXPERIMENTAL DESIGN: We enrolled 222 patients (152 in the primary cohort and 70 in the validation cohort) with clinicopathologically confirmed LARC who received chemoradiotherapy before surgery. All patients underwent T2-weighted and diffusion-weighted imaging before and after chemoradiotherapy; 2252 radiomic features were extracted from each patient pre- and post-treatment imaging...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939743/phospholipase-d1-inhibition-linked-to-upregulation-of-icat-blocks-colorectal-cancer-growth-hyperactivated-by-wnt-%C3%AE-catenin-and-pi3k-akt-signaling
#7
Dong Woo Kang, Bo Hui Lee, Young-Ah Suh, Yong-Seok Choi, Se Jin Jang, Yong-Man Kim, Kang-Yell Choi, Do Sik Min
PURPOSE: Dysregulated expression of PLD1 has emerged as a hallmark feature of colorectal cancer (CRC), which remains a major cause of mortality worldwide. Aberrant activation of Wnt/β-catenin signaling is a critical event in the development of CRC. Here, we investigated molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways via ICAT, a negative regulator of Wnt/β-catenin signaling. We also explored the effect of PLD1 inhibition on growth of CRC hyperactivated by Wnt/β-catenin and PI3K/Akt signaling...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939742/integrated-analysis-reveals-tubal-and-ovarian-originated-serous-ovarian-cancer-and-predicts-differential-therapeutic-responses
#8
Dapeng Hao, Jingjing Li, Shanshan Jia, Yuan Meng, Li Wang, Chao Zhang, Li-Jun Di
PURPOSE: The relative importance of fallopian tube (FT) compared to ovarian surface epithelium (OSE) in the genesis of serous type of ovarian cancer (SOC) is still unsettled. Here, we followed an integrated approach to study the tissue origin of SOC, as well as its association with clinical outcome and response to therapeutic drugs. EXPERIMENTAL DESIGN: A collection of transcriptome data of 80 FTs, 89 OSEs and 2,668 SOCs was systematically analyzed to determine the characteristic of FT-like and OSE-like tumors...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939741/tumor-heterogeneity-predicts-metastatic-potential-in-colorectal-cancer
#9
Je-Gun Joung, Bo Young Oh, Hye Kyung Hong, Hisham AlKhalidi, Faisal Al-Alem, Hae-Ock Lee, Joon Seol Bae, Jinho Kim, Hong-Ui Cha, Maram Alotaibi, Yong Beom Cho, Mazen Hassanain, Woo Yong Lee, Woong-Yang Park
PURPOSE: Tumors continuously evolve to maintain growth; secondary mutations facilitate this process, resulting in high tumor heterogeneity. In this study, we compared mutations in paired primary and metastatic colorectal cancer (CRC) tumor samples to determine whether tumor heterogeneity can predict tumor metastasis. EXPERIMENTAL DESIGN: Somatic variations in 46 pairs of matched primary-liver metastatic tumors and 42 primary tumors without metastasis were analyzed by whole exome sequencing...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939740/immunomodulation-by-entinostat-in-renal-cell-carcinoma-patients-receiving-high-dose-interleukin-2-a-multicenter-single-arm-phase-1-2-trial-nci-ctep-7870
#10
Roberto Pili, David I Quinn, Hans Hammers, J Paul Monk, Saby George, Tanya Dorff, Thomas Olencki, Li Shen, Ashley R Orillion, Dominick Lamonica, Roberto A Salas Fragomeni, Zsolt Szabo, Alan D Hutson, Adrienne Groman, Susan M Perkins, Richard L Piekarz, Michael A Carducci
PURPOSE: Based on preclinical data suggesting that the class I selective HDAC inhibitor entinostat exerts a synergistic antitumor effect in combination with high dose interleukin 2 (IL-2) in a renal cell carcinoma model by down-regulating Foxp3 expression and function of regulatory T cells (Treg), we conducted a phase I/II clinical study with entinostat and high dose IL-2 in patients with metastatic clear cell renal cell carcinoma (ccRCC). EXPERIMENTAL DESIGN: Clear cell histology, no prior treatments, and being sufficiently fit to receive high dose IL-2 were the main eligibility criteria...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28939739/amplification-of-1q32-1-refines-the-molecular-classification-of-endometrial-carcinoma
#11
Jeroen Depreeuw, Ellen Stelloo, Elisabeth M Osse, Carien L Creutzberg, Remi A Nout, Matthieu Moisse, Michael Dewaele, Karen Willekens, Jean-Christophe Marine, Xavier Matias-Guiu, Frederic Amant, Diether Lambrechts, Tjalling Bosse
PURPOSE: Molecular classification of endometrial cancer (EC) identified distinct molecular subgroups. However, the largest subset of ECs remains poorly characterized and is referred to as the 'non-specific molecular profile' (NSMP) subgroup. Here, we aimed at refining the classification of this subgroup by profiling somatic copy number aberrations (SCNAs). EXPERIMENTAL DESIGN: SCNAs were analyzed in 141 ECs using whole-genome SNP arrays and pooled with 361 ECs from The Cancer Genome Atlas...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928164/immunopet-of-malignant-and-normal-b-cells-with%C3%A2-89-zr-and%C3%A2-124-i-labeled-obinutuzumab-antibody-fragments-reveals-differential-cd20-internalization-in-vivo
#12
Kirstin A Zettlitz, Richard Tavare, Scott M Knowles, Kristopher K Steward, John M Timmerman, Anna M Wu
PURPOSE: The B-cell antigen CD20 provides a target for antibody-based positron emission tomography (immunoPET). We engineered antibody fragments targeting human CD20 and studied their potential as immunoPET tracers in transgenic mice (huCD20TM) and in a murine lymphoma model expressing human CD20. EXPERIMENTAL DESIGN: Anti-CD20 cys-diabody (cDb) and cys-minibody (cMb) based on rituximab (Rx) and obinutuzumab (GA101) were radioiodinated and used for immunoPET imaging of a murine lymphoma model...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928163/high-bcr-abl-gusis-levels-at-diagnosis-of-chronic-phase-cml-are-associated-with-unfavorable-responses-to-standard-dose-imatinib
#13
Paolo Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Sergio Siragusa, Donato Mannina, Stefana S Impera, Caterina Musolino, Alessandra Malato, Giuseppe Mineo, Carmela Tomaselli, Pamela Murgano, Maurizio Musso, Fortunato Morabito, Stefano Molica, Bruno Martino, Livia Manzella, Martin C Müller, Andreas Hochhaus, Francesco Di Raimondo
PURPOSE: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate Imatinib responses. EXPERIMENTAL DESIGN: We correlated BCR-ABL/GUSIS and BCR-ABL/ABLIS transcripts at diagnosis with the outcome - defined by the 2013 European LeukemiaNet recommendations - of 272 newly diagnosed CML patients receiving Imatinib 400 mg/daily...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928162/therapeutic-drug-monitoring-of-carboplatin-in-high-dose-protocol-ti-ce-for-advanced-germ-cell-tumors-pharmacokinetic-results-of-a-phase-2-multicenter-study
#14
Sotheara Moeung, Christine Chevreau, Sophie Broutin, Jérôme Guitton, Bénédicte Lelièvre, Joseph Ciccolini, Christophe Massard, Aude Fléchon, Rémy Delva, Gwenaëlle Gravis, Jean-Pierre Lotz, Jacques-Olivier Bay, Marine Gross-Goupil, Angelo Paci, Sabrina Marsili, Laurence Malard, Etienne Chatelut, Fabienne Thomas
PURPOSE: We aimed to evaluate the performance of therapeutic drug monitoring (TDM) approach in controlling inter-patient variability of carboplatin exposure (AUC) in patients treated with TI-CE high-dose chemotherapy for advanced germ cell tumors and to assess the possibility of using a formula-based dosing method as a possible alternative. EXPERIMENTAL DESIGN: Eighty nine patients receiving carboplatin for 3 consecutive days during 3 cycles were evaluable for pharmacokinetic study...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928161/the-immune-microenvironment-confers-chemoresistance-of-colorectal-cancer-through-macrophage-derived-il-6
#15
Zhaohui Huang, Yuan Yin, Surui Yao, Yaling Hu, Yuyang Feng, Min Li, Zehua Bian, Jiwei Zhang, Yan Qin, Xiaowei Qi, Le-Yuan Zhou, Bojian Fei, Jian Zou, Dong Hua
PURPOSE: Tumor-associated macrophages (TAMs) are frequently associated with poor prognosis in human cancers. However, the effects of TAM in colorectal cancer (CRC) are contradictory. We therefore investigated the functions, mechanisms and clinical significance of TAMs in CRC. EXPERIMENTAL DESIGN: We measured the macrophage infiltration (CD68), P-gp and Bcl2 expression in CRC tissues using Immunohistochemistry staining. Co-culture of TAMs and CRC cells both in vitro and in vivo models was used to evaluate the effects of TAMs on CRC chemoresistance...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928160/quantitative-and-mechanistic-understanding-of-azd1775-penetration-across-human-blood-brain-barrier-in-glioblastoma-patients-using-an-ivive-pbpk-modeling-approach
#16
Jing Li, Jianmei Wu, Xun Bao, Norissa Honea, Youming Xie, Seongho Kim, Alex Sparreboom, Nader Sanai
PURPOSE: AZD1775, a first-in-class, small molecule inhibitor of the Wee1 tyrosine kinase, is under evaluation as a potential chemo- and radio-sensitizer for treating glioblastoma. This study was to prospectively, quantitatively, and mechanistically investigate the penetration of AZD1775 across human blood-brain barrier (BBB). EXPERIMENTAL DESIGN: AZD1775 plasma and tumor pharmacokinetics were evaluated in 20 glioblastoma patients. The drug metabolism, transcellular passive permeability, and interactions with efflux and uptake transporters were determined using human derived in vitro systems...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928159/bmp4-induces-m2-macrophage-polarization-and-favors-tumor-progression-in-bladder-cancer
#17
Víctor G Martínez, Carolina Rubio, Mónica Martínez-Fernández, Cristina Segovia, Fernando López-Calderón, Marina Garín, Alicia Teijeira, Ester Munera-Maravilla, Alberto Varas, Rosa Sacedón, Felix Guerrero-Ramos, Felipe Villacampa, Federico de la Rosa, Daniel Castellano, Eduardo López-Collazo, Jesus M Paramio, Ángeles Vicente, Marta Dueñas
PURPOSE: Bladder cancer (BC) is a current clinical and social problem. At diagnosis, most patients present non-muscle invasive tumors, characterized by a high recurrence rate, which could progress to muscle invasive disease and metastasis. Bone morphogenetic protein (BMP)-dependent signaling arising from stromal bladder tissue mediates urothelial homeostasis by promoting urothelial cell differentiation. However, the possible role of BMP ligands in BC is still unclear. EXPERIMENTAL DESIGN: Tumor and normal tissue from 68 patients with urothelial cancer were prospectively collected and analyzed for expression of BMP and macrophage markers...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#18
Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis Taube, Robert A Anders
PURPOSE: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. EXPERIMENTAL DESIGN: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. RESULTS: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916527/demethylation-therapy-as-a-targeted-treatment-for-human-papilloma-virus-associated-head-and-neck-cancer
#19
Asel K Biktasova, Michael Hajek, Andrew B Sewell, Cyril S Gary, Gary Bellinger, Hari Deshpande, Aarti K Bhatia, Barbara A Burtness, Benjamin L Judson, Saral Mehra, Wendell G Yarbrough, Natalia Issaeva
PURPOSE: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation and survival. Here, we determined activity of a global DNA demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in pre-clinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC. EXPERIMENTAL DESIGN: Sensitivity of HNSCC cells to 5-aza treatment was determined, then 5-aza activity was tested in vivo using xenografted tumors in a mouse model...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#20
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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