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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/28228384/impact-of-disseminated-neuroblastoma-cells-on-the-identification-of-the-relapse-seeding-clone
#1
M Reza Abbasi, Fikret Rifatbegovic, Clemens Brunner, Georg Mann, Andrea Ziegler, Ulrike Pötschger, Roman Crazzolara, Marek Ussowicz, Martin Benesch, Georg Ebetsberger-Dachs, Godfrey Chi-Fung Chan, Neil Jones, Ruth Ladenstein, Inge M Ambros, Peter F Ambros
PURPOSE: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones. EXPERIMENTAL DESIGN: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients. RESULTS: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples...
February 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223275/vascular-cxcr4-expression-promotes-vessel-sprouting-and-sensitivity-to-sorafenib-treatment-in-hepatocellular-carcinoma
#2
Jing Xu, Jing Liang, Ya-Ming Meng, Jing Yan, Xin-Juan Yu, Chao-Qun Liu, Li Xu, Shi-Mei Zhuang, Limin Zheng
PURPOSE: Chemokine receptor CXCR4 is known to be involved in both developmental and adult angiogenesis; however, its role in tumor angiogenesis remains largely unknown. Here the role of vascular CXCR4 in regulating vascular structure in HCC was assessed and the clinical value of CXCR4 was explored. EXPERIMENTAL DESIGN: The expression of CXCR4 in hepatocellular carcinoma (HCC) was determined by immunohistochemistry and immunofluorescence. Characteristics of CXCR4+ cells were determined by in vitro and mice experiments...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223274/long-term-responders-on-olaparib-maintenance-in-high-grade-serous-ovarian-cancer-clinical-and-molecular-characterization
#3
Stephanie Lheureux, Zhongwu Lai, Brian A Dougherty, Sarah Runswick, Darren Hodgson, Kirsten M Timms, Jerry S Lanchbury, Stanley B Kaye, Charlie Gourley, David D L Bowtell, Elise C Kohn, Clare L Scott, Ursula A Matulonis, Tony Panzarella, Katherine Karakasis, Julia V Burnier, Blake Gilks, Mark J O'Connor, Jane D Robertson, Jonathan Ledermann, J Carl Barrett, Tony W Ho, Amit M Oza
PURPOSE: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. EXPERIMENTAL DESIGN: A comparative molecular analysis of Study 19 (NCT00753545), a randomized Phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28223273/pd-l1-studies-across-tumor-types-its-differential-expression-and-predictive-value-in-patients-treated-with-immune-checkpoint-inhibitors
#4
Harriet M Kluger, Christopher R Zito, Gabriela Turcu, Marina Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L Rimm, Yuval Kluger, Lieping Chen, Justine V Cohen, Lucia B Jilaveanu
PURPOSE: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), extensive efforts are underway to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than RCC or melanoma. We therefore studied differences in expression patterns across tumor types. EXPERIMENTAL DESIGN: We employed tissue microarrays with tumors from NSCLC, RCC or melanoma and a panel of cell lines to study differences between tumor types...
February 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#5
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213365/fda-approval-summary-tas-102
#6
Leigh Marcus, Steven J Lemery, Sachia Khasar, Emily Wearne, Whitney S Helms, Weishi Yuan, Kun He, Xianhua Cao, Jingyu Yu, Hong Zhao, Yaning Wang, Olen Stephens, Erika Englund, Rajiv Agarwal, Patricia Keegan, Richard Pazdur
FDA approved TAS-102 (Lonsurf, Taiho Oncology, Inc.) for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In an international, multicenter, double-blinded, placebo-controlled trial (TPU-TAS-102-301, herein referred to as RECOURSE), 800 patients with previously treated mCRC were randomly allocated (2:1) to receive either TAS-102 35mg/m2 orally twice daily after meals on Days 1-5 and 8-12 of each 28-day cycle (n=534) or matching placebo (n=266)...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28213364/safety-and-antitumor-activity-of-apalutamide-arn-509-in-metastatic-castration-resistant-prostate-cancer-with-and-without-prior-abiraterone-acetate-and-prednisone
#7
Dana E Rathkopf, Emmanuel S Antonarakis, Neal D Shore, Ronald F Tutrone, Joshi J Alumkal, Charles J Ryan, Mansoor Saleh, Ralph J Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla J de Boer, Margaret K Yu, Howard I Scher
PURPOSE: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL DESIGN: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28196874/prospective-evaluation-of-sunitinib-induced-cardiotoxicity-in-patients-with-metastatic-renal-cell-carcinoma
#8
Vivek Narayan, Stephen M Keefe, Naomi Haas, Le Wang, Igor Puzanov, Mary E Putt, Anna Catino, James Fang, Neeraj Agarwal, David Hyman, Amanda M Smith, Brian S Finkelman, Hari K Narayan, Steven Ewer, Chantal ElAmm, Daniel J Lenihan, Bonnie Ky
PURPOSE: To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping. PATIENTS AND METHODS: In a multi-center prospective study of 90 mRCC patients, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These "on-drug" visits corresponded to cycles 1, 3, and 6, respectively...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28196873/lymphotoxin-beta-interacts-with-methylated-egfr-to-mediate-acquired-resistance-to-cetuximab-in-head-and-neck-cancer
#9
Dennis Shin-Shian Hsu, Wei-Lun Hwang, Chiou-Hwa Yuh, Chen-Hsi Chu, Yang-Hui Ho, Pon-Bo Chen, Han-Syuan Lin, Hua-Kuo Lin, Shih-Pei Wu, Chih-Yi Lin, Wen-Hao Hsu, Hsin-Yi Lan, Hsiao-Jung Wang, Shyh-Kuan Tai, Mien-Chie Hung, Muh-Hwa Yang
PURPOSE: In head and neck squamous cell carcinoma (HNSCC), the incidence of RAS mutation, which is the major cause of cetuximab resistance, is relatively rare compared with the other types of cancers, and the mechanism mediating acquired resistance is unclear compared with the driver gene mutation-mediated de novo resistance. Here we investigated the driver gene mutation-independent mechanism for cetuximab resistance in HNSCC. EXPERIMENTAL DESIGN: We used the in vitro-selected and in vivo-selected cetuximab-resistant sublines of HNSCC cell lines for investigating the mechanism of acquired resistance to cetuximab...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28196872/muc16-regulates-tspyl5-for-lung-cancer-cell-growth-and-chemoresistance-by-suppressing-p53
#10
Imayavaramban Lakshmanan, Shireen Salfity, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Abigail Thomas, Srustidhar Das, Prabin D Majhi, Rama Krishna Nimmakayala, Raghupathy Vengoji, Subodh M Lele, Moorthy P Ponnusamy, Surinder K Batra, Apar Kishor Ganti
PURPOSE: MUC16, a tumor biomarker and cell surface associated mucin, is overexpressed in various cancers; however, its role in lung cancer pathogenesis is unknown. Here, we have explored the mechanistic role of MUC16 in lung cancer. EXPERIMENTAL DESIGN: To identify the functional role of MUC16, stable knockdown was carried in lung cancer cells with two different shRNAs. Clinical significance of MUC16 was evaluated in lung cancer patient's tissues using IHC. We have generated genetically engineered mouse model (KrasG12D; AdCre) to evaluate the preclinical significance of MUC16...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28193627/adoptive-transfer-of-invariant-nkt-cells-as-immunotherapy-for-advanced-melanoma-a-phase-1-clinical-trial
#11
Mark A Exley, Philip Friedlander, Nadia Alatrakchi, Lianne Vriend, Simon C Yue, Tetsuro Sasada, Wanyong Zang, Yo Mizukami, Justice Clark, David Nemer, Ken LeClair, Christine Canning, Heather Daley, Glenn Dranoff, Anita Giobbie-Hurder, F Stephen Hodi, Jerome Ritz, Steven P Balk
PURPOSE: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown responses. Therefore, a phase 1 clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28193626/autologous-heat-shock-protein-peptide-vaccination-for-newly-diagnosed-glioblastoma-impact-of-peripheral-pd-l1-expression-on-response-to-therapy
#12
Orin Bloch, Michael Lim, Michael E Sughrue, Ricardo J Komotar, John M Abrahams, Donald M O'Rourke, Anthony D'Ambrosio, Jeffrey N Bruce, Andrew T Parsa
PURPOSE: Standard therapy for newly diagnosed glioblastoma (GBM) is surgical resection, followed by concurrent radiotherapy and temozolomide chemotherapy. In this phase 2 clinical trial, the addition of an autologous heat shock protein vaccine to standard therapy was evaluated. Tumor-induced immunosuppression, mediated by expression of PD-L1 on tumor and circulating immune cells, may impact the efficacy of vaccination. Expression of PD-L1 on peripheral myeloid cells was evaluated for the first time as a predictor of survival...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28193625/deep-sequencing-of-urinary-rnas-for-bladder-cancer-molecular-diagnostics
#13
Mandy L Y Sin, Kathleen E Mach, Rahul Sinha, Fan Wu, Dharati Trivedi, Emanuela Altobelli, Kristin C Jensen, Debashis Sahoo, Ying Lu, Joseph C Liao
PURPOSE: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. EXPERIMENTAL DESIGN: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients (n=13) and controls (n=10)...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28193624/transcriptional-mechanisms-of-resistance-to-anti-pd-1-therapy
#14
Maria Libera Ascierto, Alvin Makohon-Moore, Evan J Lipson, Janis M Taube, Tracee L McMiller, Alan E Berger, Jinshui Fan, Genevieve Kaunitz, Tricia Cottrell, Zachary Kohutek, Alexander Favorov, Vladimir Makarov, Nadeem Riaz, Timothy A Chan, Leslie Cope, Ralph H Hruban, Drew M Pardoll, Barry S Taylor, David B Solit, Christine A Iacobuzio-Donahue, Suzanne L Topalian
PURPOSE: To explore factors associated with response and resistance to anti-PD-1 therapy, we analyzed multiple disease sites at autopsy in a patient with widely metastatic melanoma who had a heterogeneous response. MATERIALS AND METHODS: Twenty-six melanoma specimens (four pre-mortem, 22 post-mortem) were subjected to whole-exome sequencing. Candidate immunologic markers and gene expression were assessed in ten cutaneous metastases showing response or progression during therapy...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28183714/dichotomous-alk-ihc-is-a-better-predictor-for-alk-inhibition-outcome-than-traditional-alk-fish-in-advanced-non-small-cell-lung-cancer
#15
Anthonie van der Wekken, Rianne Pelgrim, Nils 't Hart, Naomi Werner, Mirjam Mastik, Lizza Hendriks, Erik Hfm van der Heijden, Monika Looijen-Salamon, A Joop de Langen, Jeske Staal-van den Brekel, Sietske Riemersma, Ben E van den Borne, Ernst-Jan M Speel, Anne-Marie C Dingemans, T Jeroen N Hiltermann, Anke van den Berg, Wim Timens, Ed Schuuring, Harry Jm Groen
ALK rearrangement detection using fluorescence in situ hybridization (FISH) is the standard test to identify non-small cell lung carcinoma (NSCLC) patients eligible for treatment with ALK inhibitors. Recently ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of advanced NSCLC patients with ALK activation using both dichotomous immunohistochemical staining (IHC) and FISH. Design Stage IV NSCLC patients treated with crizotinib were selected...
February 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28183713/vaccination-targeting-native-receptors-to-enhance-the-function-and-proliferation-of-chimeric-antigen-receptor-car-modified-t-cells
#16
Miyuki Tanaka, Haruko Tashiro, Bilal Omer, Natasha Lapteva, Jun Ando, Minhtran Ngo, Birju Mehta, Gianpietro Dotti, Paul R Kinchington, Ann M Leen, Claudia Rossig, Cliona M Rooney
PURPOSE: The multiple mechanisms used by solid tumors to suppress tumor-specific immune responses are a major barrier to the success of adoptively-transferred tumor-specific T-cells. Since viruses induce potent innate and adaptive immune responses, we hypothesized that the immunogenicity of viruses could be harnessed for the treatment of solid tumors if virus-specific T-cells (VSTs) were modified with tumor-specific chimeric antigen receptors (CARs). We tested this hypothesis using VZV-specific T-cells (VZVSTs) expressing a CAR for GD2, a disialoganglioside expressed on neuroblastoma and certain other tumors, since the live-attenuated VZV vaccine could be used for in vivo stimulation...
February 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28179454/fda-approval-summary-pembrolizumab-for-the-treatment-of-patients-with-unresectable-or-metastatic-melanoma
#17
Amy Barone, Maitreyee Hazarika, Marc R Theoret, Pallavi Mishra-Kalyani, Huanyu Chen, Kun He, Rajeshwari Sridhara, Sriram Subramaniam, Elimika Pfuma, Yaning Wang, Hongshan Li, Hong Zhao, Jeanne Fourie Zirkelbach, Patricia Keegan, Richard Pazdur
On December 18, 2015, the U.S. Food and Drug Administration (FDA) granted regular approval to pembrolizumab (KEYTRUDA®; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma, based on results of two randomized, open-label, active-controlled clinical trials. In Trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg intravenously (IV) every 2 (q2w) or 3 (q3w) weeks until disease progression or ipilimumab 3 mg/kg q3w for up to four doses...
February 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28174236/merkel-cell-carcinomas-arising-in-autoimmune-disease-affected-patients-treated-with-biological-drugs-including-tnf
#18
John C Rotondo, Ilaria Bononi, Andrea Puozzo, Marcello Govoni, Valentina Foschi, Giovanni Lanza, Roberta Gafà, Antoine Touzè, Pauline Gaboriaud, Rita Selvatici, Fernanda Martini, Mauro Tognon
PURPOSE: The purpose of this investigation was to characterize Merkel cell carcinomas (MCC) arising in patients affected by auto-immune diseases, treated with biologic drugs. EXPERIMENTAL DESIGN: Serum samples from MCC patients were analyzed for the presence and titer of antibodies against antigens of the oncogenic Merkel cell polyomavirus (MCPyV). IgG antibodies against the viral oncoproteins Large T (LT) and small t (ST) antigens and the viral capsid protein 1 were analyzed by indirect E...
February 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28174235/an-integrated-approach-identifies-mediators-of-local-recurrence-in-head-neck-squamous-carcinoma
#19
Francesca Citron, Joshua Armenia, Giovanni Franchin, Jerry Polesel, Renato Talamini, Sara D'Andrea, Sandro Sulfaro, Carlo M Croce, William Klement, Dave Otasek, Chiara Pastrello, Tomas Tokar, Igor Jurisica, Deborah French, Riccardo Bomben, Emanuela Vaccher, Diego Serraino, Barbara Belletti, Andrea Vecchione, Luigi Barzan, Gustavo Baldassarre
PURPOSE: Head and Neck Squamous Cell Carcinomas (HNSCC) cause more than 300,000 deaths worldwide each year. Locoregional and distant recurrences represent worse prognostic events and accepted surrogate markers of patients' survival. No valid biomarker and salvage therapy exist to identify and treat patients at high-risk of recurrence. We aimed to verify if selected microRNAs (miRs) could be used as biomarkers of recurrence in HNSCC. EXPERIMENTAL DESIGN: A Nanostring array was used to identify miRs associated with locoregional recurrence in 44 HNSCC patients...
February 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28174234/ct-perfusion-as-an-early-biomarker-of-treatment-efficacy-in-advanced-ovarian-cancer-an-acrin-and-gog-study
#20
Chaan Ng, Zheng Zhang, Susanna I Lee, Helga S Marques, Kyle Burgers, Feng Su, Joseph Bauza, Robert S Mannel, Joan Walker, Warner K Huh, Stephen C Rubin, Paul DiSilvestro, Lainie P Martin, John K Chan, Michael A Bookman, Robert L Coleman, Ting-Yim Lee
PURPOSE: ACRIN 6695 was a feasibility study investigating whether CT perfusion (CTP) biomarkers are associated with progression-free survival at 6 months (PFS-6) in patients with advanced ovarian cancer who were treated with carboplatin and either dose-dense (weekly) or conventional (3-weekly) paclitaxel, with optional bevacizumab in the prospective phase III GOG-0262 trial. EXPERIMENTAL DESIGN: ACRIN 6695 recruited participants with residual disease after primary cytoreductive surgery or planned interval cytoreduction following neoadjuvant therapy, to undergo CTP studies before (T0), 3-weeks (T1) and 4-weeks (T2) after chemotherapy initiation...
February 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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