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https://www.readbyqxmd.com/read/28331530/kras-detection-on-archival-cytological-smears-by-the-novel-fully-automated-polymerase-chain-reaction-based-idylla-mutation-test
#1
Caterina De Luca, Elena Vigliar, Melania d'Anna, Pasquale Pisapia, Claudio Bellevicine, Umberto Malapelle, Giancarlo Troncone
BACKGROUND: Molecular techniques are relevant to modern cytopathology, but their implementation is difficult without molecular expertise and infrastructure. The assessment of KRAS mutational status on cytological preparations may be useful either to refine uncertain diagnoses on pancreatic aspirates or to yield predictive information to plan targeted treatment of metastatic colorectal cancer (mCRC). The novel test Idylla™ enables fully automated KRAS genotyping in approximately 2 h, even in less experienced hands...
2017: CytoJournal
https://www.readbyqxmd.com/read/28328812/overall-survival-of-patients-with-kras-wild-type-tumor-treated-with-folfox-forfiri%C3%A2-cetuximab-as-the-first-line-treatment-for-metastatic-colorectal-cancer-a-meta-analysis
#2
Ya-Fan Yang, Gui-Ying Wang, Jing-Li He, Feng-Peng Wu, Yan-Ni Zhang
The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ± cetuximab was compared...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28323034/co-targeting-of-egfr-and-autophagy-signaling-is-an-emerging-treatment-strategy-in-metastatic-colorectal-cancer
#3
Evangelos Koustas, Michalis V Karamouzis, Chrysovalantou Mihailidou, Dimitrios Schizas, Athanasios G Papavassiliou
The epidermal growth factor receptor (EGFR) and its associated pathway is a critical key regulator of CRC development and progression. The monoclonal antibodies (MoAbs) cetuximab and panitumumab, directed against EGFR, represent a major step forward in the treatment of metastatic colorectal cancer (mCRC), in terms of progression-free survival and overall survival in several clinical trials. However, the activity of anti-EGFR MoAbs appears to be limited to a subset of patients with mCRC. Studies have highlighted that acquired-resistance to anti-EGFR MoAbs biochemically converge into Ras/Raf/Mek/Erk and PI3K/Akt/mTOR pathways...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315543/metastatic-colorectal-cancer-management-with-trifluridine-tipiracil%C3%A2
#4
Teresa White, Heidi Larson, Alexandra Minnella, Howard S Hochster
BACKGROUND: Treatment-related adverse events (AEs) are common in patients with metastatic colorectal cancer (mCRC) receiving chemotherapy. These AEs may affect patient adherence, particularly with completely oral regimens, such as trifluridine/tipiracil (TAS-102, Lonsurf®), an antimetabolite agent for patients with mCRC refractory or intolerant to standard therapies.
. OBJECTIVES: This article reviews strategies for promoting adherence and educating patients and caregivers about oral therapy with trifluridine/tipiracil...
April 1, 2017: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/28303751/vasoactive-peptides-associate-with-treatment-outcome-ofbevacizumab-containing-therapy-in-metastatic-colorectal-cancer
#5
Helga Hagman, Pär-Ola Bendahl, Olle Melander, Jan Sundberg, Anders Johnsson, Mattias Belting
BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer...
March 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28299879/how-accurate-are-medical-oncologists-impressions-of-management-of-metastatic-colorectal-cancer-in-australia
#6
Lewis Au, Natalie Turner, Hui-Li Wong, Kathryn Field, Belinda Lee, David Boadle, Prasad Cooray, Deme Karikios, Suzanne Kosmider, Lara Lipton, Louise Nott, Phillip Parente, Jeanne Tie, Ben Tran, Rachel Wong, Desmond Yip, Jeremy Shapiro, Peter Gibbs
AIM: Current efforts to understand patient management in clinical practice are largely based on clinician surveys with uncertain reliability. The TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database is a multisite registry collecting comprehensive treatment and outcome data on consecutive metastatic colorectal cancer (mCRC) patients at multiple sites across Australia. This study aims to determine the accuracy of oncologists' impressions of real-word practice by comparing clinicians' estimates to data captured by TRACC...
March 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28292509/impact-of-serum-apolipoprotein-a-i-on-prognosis-and-bevacizumab-efficacy-in-patients-with-metastatic-colorectal-cancer-a-propensity-score-matched-analysis
#7
Qi Quan, Yuanyuan Huang, Qi Chen, Huijuan Qiu, Qiaozhen Hu, Yuming Rong, Tingwei Li, Liangping Xia, Bei Zhang
PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I) as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low- and high-ApoA-I groups...
April 2017: Translational Oncology
https://www.readbyqxmd.com/read/28280611/baseline-hemoglobin-and-liver-function-predict-tolerability-and-overall-survival-of-patients-receiving-radioembolization-for-chemotherapy-refractory-metastatic-colorectal-cancer
#8
Andrew S Kennedy, David Ball, Steven J Cohen, Michael Cohn, Douglas M Coldwell, Alain Drooz, Edward Ehrenwald, Samir Kanani, Fred M Moeslein, Charles W Nutting, Samuel G Putnam, Steven C Rose, Michael Savin, Sabine Schirm, Navesh K Sharma, Eric Wang
BACKGROUND: Patients with liver metastatic colorectal cancer (mCRC) often benefit from receiving (90)Y-microsphere radioembolization (RE) administered via the hepatic arteries. Prior to delivery of liver-directed radiation, standard laboratory tests may assist in improving outcome by identifying correctable pre-radiation abnormalities. METHODS: A database containing retrospective review of consecutively treated patients of mCRC from July 2002 to December 2011 at 11 US institutions was used...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#9
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28280091/dual-inhibition-of-egfr-and-c-src-by-cetuximab-and-dasatinib-combined-with-folfox-chemotherapy-in-patients-with-metastatic-colorectal-cancer
#10
Christine Parseghian, Nila U Parikh, Ji Yuan Wu, Zhi-Qin Jiang, Laura D Henderson, Feng Tian, Brice Pastor, Marc Ychou, Kanwal Raghav, Arvind Dasari, David Fogelman, Anastasia Katsiampoura, David G Menter, Robert A Wolff, Cathy Eng, Michael J Overman, Alain R Thierry, Gary E Gallick, Scott Kopetz
BACKGROUND: Aberrant activation of the intracellular tyrosine kinase Src has been implicated as a mechanism of acquired chemotherapy resistance in metastatic colorectal cancer (mCRC). Here, the oral tyrosine kinase Src inhibitor, dasatinib, was investigated in combination with FOLFOX and cetuximab. METHODS: We performed a phase IB/II study of 77 patients with previously-treated mCRC. Primary objectives were to determine the MTD, dose-limiting-toxicities, pharmacodynamics, and efficacy...
March 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28277294/observational-cohort-study-of-patients-with-metastatic-colorectal-cancer-initiating-chemotherapy-in-combination-with-bevacizumab-concert
#11
Jaafar Bennouna, Jean-Marc Phelip, Thierry André, Bernard Asselain, Sébastien Koné, Michel Ducreux
BACKGROUND: The CONCERT study (observational cohort study of patients with metastatic colorectal cancer initiating chemotherapy in combination with bevacizumab) aimed to describe patient characteristics, bevacizumab use, its efficacy in terms of progression-free survival (PFS) and overall survival (OS), and its safety in patients with metastatic colorectal cancer (mCRC) treated in daily medical practice. PATIENTS AND METHODS: CONCERT was an observational, prospective, multicenter, cohort study conducted in France...
August 9, 2016: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28275117/randomized-phase-ii-trial-of-parsatuzumab-anti-egfl7-or-placebo-in-combination-with-folfox-and-bevacizumab-for-first-line-metastatic-colorectal-cancer
#12
Rocío García-Carbonero, Eric van Cutsem, Fernando Rivera, Jacek Jassem, Ira Gore, Niall Tebbutt, Fadi Braiteh, Guillem Argiles, Zev A Wainberg, Roel Funke, Maria Anderson, Bruce McCall, Mark Stroh, Eric Wakshull, Priti Hegde, Weilan Ye, Daniel Chen, Ilsung Chang, Ina Rhee, Herbert Hurwitz
LESSONS LEARNED: These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents. BACKGROUND: EGFL7 (epidermal growth factor-like domain 7) is a tumor-enriched vascular extracellular matrix protein that supports endothelial cell survival...
March 8, 2017: Oncologist
https://www.readbyqxmd.com/read/28275038/an-expanding-role-for-immunotherapy-in-colorectal-cancer
#13
REVIEW
Katherine M Bever, Dung T Le
Colorectal cancer (CRC) is a leading cause of cancer-related mortality in the United States. Response rates to second- and third-line therapy for metastatic CRC (mCRC) remain low, and immunotherapy is an attractive strategy for treatment in these patients given generally better tolerability than conventional chemotherapy and the potential for long-lasting durable responses. In particular, the novel checkpoint inhibitors (CPIs) have demonstrated unprecedented clinical activity in a wide range of cancers. The observation of clinical activity in microsatellite instability-high (MSI-H) mCRC was the first indication of a potential for CRC to respond to these agents, and has led to a breakthrough designation by the FDA for CPI use in this subset...
March 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28274890/metronomic-chemotherapy-in-metastatic-colorectal-cancer
#14
In Sook Woo, Yun Hwa Jung
Overall survival and quality of life of patients with metastatic colorectal cancer (mCRC) have improved due to the development of standard systemic treatment. However, many patients are still suffering from the eventual progression of cancer, treatment-related toxicities, and the economic burden of new drugs. Salvage or maintenance therapy, which consistently controls or stabilizes tumor progression without debilitating quality of life, is required. Recently, metronomic capecitabine maintenance therapy after disease control using conventional chemotherapy with maximal tolerated doses has demonstrated beneficial results in a phase III trial...
March 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28261339/primary-tumor-location-as-a-predictive-factor-for-first-line-bevacizumab-effectiveness-in-metastatic-colorectal-cancer-patients
#15
Wen-Zhuo He, Fang-Xin Liao, Chang Jiang, Peng-Fei Kong, Chen-Xi Yin, Qiong Yang, Hui-Juan Qiu, Bei Zhang, Liang-Ping Xia
Background: Published papers reported contradictory results about the correlation between bevacizumab effectiveness and primary tumor location of metastatic colorectal cancer (mCRC). Methods: 740 mCRC patients treated with chemotherapy (CT group) and 244 patients treated with bevacizumab plus chemotherapy as first-line setting (CT + B group) were included. Propensity score analyses were used for patients' stratification and matching. Kaplan-Meier curves with log-rank tests were used to detect different overall survival (OS)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28237539/rationale-for-and-design-of-the-paradigm-study-randomized-phase-iii-study-of-mfolfox6-plus-bevacizumab-or-panitumumab-in-chemotherapy-na%C3%A3-ve-patients-with-ras-kras-nras-wild-type-metastatic-colorectal%C3%A2-cancer
#16
Takayuki Yoshino, Hiroyuki Uetake, Katsuya Tsuchihara, Kohei Shitara, Kentaro Yamazaki, Eiji Oki, Takeo Sato, Takeshi Naitoh, Yoshito Komatsu, Takeshi Kato, Kazunori Yamanaka, Kouji Iwasaki, Jumpei Soeda, Masamitsu Hihara, Takeharu Yamanaka, Atsushi Ochiai, Kei Muro
BACKGROUND: It remains unclear whether an anti-VEGF or anti-EGFR antibody with standard doublet chemotherapy is the optimal first-line treatment in patients with RAS (KRAS/NRAS) wild-type metastatic colorectal cancer (mCRC). Here we outline the PARADIGM study (NCT02394795), designed to evaluate the superiority of panitumumab over bevacizumab, in combination with oxaliplatin/5-fluorouracil/leucovorin (mFOLFOX6) in patients with RAS wild-type chemotherapy-naïve mCRC. PATIENTS AND METHODS: Eligible patients are aged 20 to 79 years with an ECOG performance status of 0-1 and histologically/cytologically confirmed RAS wild-type mCRC...
January 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28223103/her2-amplification-and-cetuximab-efficacy-in-patients-with-metastatic-colorectal-cancer-harboring-wild-type-ras-and-braf
#17
Jae Ho Jeong, Jihun Kim, Yong Sang Hong, Dalyong Kim, Jeong Eun Kim, Sun Young Kim, Kyu-Pyo Kim, Young-Kwang Yoon, Deokhoon Kim, Sung-Min Chun, Yangsoon Park, Se Jin Jang, Tae Won Kim
BACKGROUND: Cetuximab has shown clinical benefit in patients with metastatic colorectal cancer (mCRC) harboring wild-type RAS. Human epidermal growth factor receptor 2 (HER2) amplification may be a mechanism of cetuximab resistance. We evaluated the association between HER2 amplification and cetuximab efficacy in patients with mCRC harboring wild-type RAS and BRAF. PATIENTS AND METHODS: Between December 2003 and June 2013, we identified 142 patients with mCRC whose tumors harbored both wild-type exons 2, 3, and 4 in KRAS and NRAS, and wild-type exon 15 in BRAF using high throughput sequencing (OncoMap version 4...
January 25, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28220486/cetuximab-plus-irinotecan-versus-panitumumab-in-patients-with-refractory-metastatic-colorectal-cancer-in-ontario-canada
#18
Katarzyna J Jerzak, Scott Berry, Yoo-Joung Ko, Craig Earle, Kelvin K W Chan
The addition of irinotecan to an epidermal growth factor receptor (EGFR) antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real-world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada, universal public funding is available for either cetuximab plus irinotecan (Cmab + I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory nonmutated RAS mCRC...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28220124/in-vivo-efficacy-of-umbilical-cord-blood-stem-cell-derived-nk-cells-in-the-treatment-of-metastatic-colorectal-cancer
#19
John P Veluchamy, Silvia Lopez-Lastra, Jan Spanholtz, Fenna Bohme, Nina Kok, Daniëlle A M Heideman, Henk M W Verheul, James P Di Santo, Tanja D de Gruijl, Hans J van der Vliet
Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RAS(wt) metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28218790/differential-expression-of-hent1-and-hent2-in-colon-cancer-cell-lines
#20
Y Liu, T Zuo, X Zhu, N Ahuja, T Fu
Human equilibrative nucleoside transporters (hENT) 1 and 2, encoded by SLC29A1 and SLC29A2, permit the bidirectional passage of nucleoside analogues into cells and may correlate with clinical responses to chemotherapy in patients with colorectal cancer (CRC). The purpose of this study was to evaluate the expression profiles of SLC29A1 and SLC29A2 in human cancer cell lines. Using quantitative real-time polymerase chain reaction, we comprehensively profiled the transcription levels of SLC29A1 and SLC29A2 in 16 colon cancer cell lines...
February 16, 2017: Genetics and Molecular Research: GMR
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