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Metastatic colorectal cancer

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https://www.readbyqxmd.com/read/28449055/primary-tumor-sidedness-has-an-impact-on-prognosis-and-treatment-outcome-in-metastatic-colorectal-cancer-results-from-two-randomized-first-line-panitumumab-studies
#1
N Boeckx, R Koukakis, K Op de Beeck, C Rolfo, G Van Camp, S Siena, J Tabernero, J-Y Douillard, T André, M Peeters
Background: : Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Material and methods: Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients...
April 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28447739/neural-precursor-cell-expressed-developmentally-downregulated-8%C3%A2-activating-enzyme-inhibitor-mln4924-sensitizes-colorectal-cancer-cells-to-oxaliplatin-by-inducing-dna-damage-g2-cell-cycle-arrest-and-apoptosis
#2
Wanwei Zheng, Zhongguang Luo, Jun Zhang, Pei Min, Wenshuai Li, Diannan Xu, Ziqiang Zhang, Panpan Xiong, Hong Liang, Jie Liu
Oxaliplatin-based chemotherapy is a primary treatment for patients with metastatic colorectal cancer (CRC); however, its efficacy is limited. Therefore, novel therapeutic agents are urgently required. MLN4924 is a first‑in‑class inhibitor of neural precursor cell expressed, developmentally downregulated 8 (NEDD8)‑activating enzyme E1, and has entered various phase‑I/II clinical trials for cancer therapy due to its significant anticancer efficacy. The aim of the present study was to examine the synergistic effect and underlying mechanisms of MLN4924 and oxaliplatin combined treatment for CRC...
March 9, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447565/risk-factors-for-brain-metastases-in-patients-with-metastatic-colorectal-cancer
#3
Troels Dreier Christensen, Jesper Andreas Palshof, Finn Ole Larsen, Estrid Høgdall, Tim Svenstrup Poulsen, Per Pfeiffer, Benny Vittrup Jensen, Mette Karen Yilmaz, Ib Jarle Christensen, Dorte Nielsen
BACKGROUND: Brain metastases (BM) from colorectal cancer (CRC) are rare, but the incidence is suspected to rise as treatment of metastatic (m) CRC improves. The aim of this study was to identify possible biological and clinical characteristics at initial presentation of mCRC that could predict later risk of developing BM. Furthermore, we wished to estimate the incidence of BM in long-term surviving patients. MATERIAL AND METHODS: We conducted a retrospective study on a Danish multicenter cohort of patients with mCRC who received cetuximab and irinotecan (CetIri) as third-line treatment...
May 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28446505/clinical-features-and-outcomes-of-patients-with-colorectal-cancers-harboring-nras-mutations
#4
Andrea Cercek, Maria Ignez Braghiroli, Joanne F Chou, Jaclyn F Hechtman, Nancy E Kemeny, Leonard Saltz, Marinela Capanu, Rona Yaeger
Purpose: NRAS mutations are now routinely included in RAS testing prior to EGFR (epidermal growth factor receptor) inhibitor therapy for metastatic colorectal cancer (mCRC).  The clinical implications of NRAS mutation beyond lack of response to anti-EGFR therapy, however, are not known.  We undertook this study to determine the clinical features and treatment outcomes of patients with NRAS mutant mCRC.<br />Experimental Design: We reviewed clinical characteristics, concurrent mutations, and outcomes for all mCRC cases with NRAS mutations undergoing standard genotyping at our institution from 2008-2015...
April 26, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28445892/feasibility-of-modified-folfox-in-elderly-patients-aged-%C3%A2-80-years-with-metastatic-gastric-cancer-or-colorectal-cancer
#5
Kyu-Hyoung Lim, Hui-Young Lee, Sung Bae Park, Seo-Young Song
OBJECTIVE: The aim of this study was to assess the feasibility of a modified FOLFOX regimen as first-line treatment in elderly patients with metastatic gastric cancer (GC) or colorectal cancer (CRC). METHODS: We included chemotherapy-naïve patients over 80 years old with metastatic GC or CRC in our study. From September 2008 to November 2014, 28 consecutive patients were enrolled and treated with modified FOLFOX. RESULTS: The study population consisted of an equal number of GC and CRC patients...
April 27, 2017: Oncology
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#6
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#7
Anup Sharma, Rajita Vatapalli, Eihab Abdelfatah, K Wyatt McMahon, Zachary Kerner, Angela A Guzzetta, Jasvinder Singh, Cynthia Zahnow, Stephen B Baylin, Sashidhar Yerram, Yue Hu, Nilofer Azad, Nita Ahuja
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#8
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28444508/study-protocol-on-the-role-of-intestinal-microbiota-in-colorectal-cancer-treatment-a-pathway-to-personalized-medicine-2-0
#9
R Aarnoutse, J M P G M de Vos-Geelen, J Penders, E G Boerma, F A R M Warmerdam, B Goorts, S W M Olde Damink, Z Soons, S S M Rensen, M L Smidt
PURPOSE: Investigate in patients with metastatic and/or irresectable colorectal cancer treated with systemic treatment with capecitabine or TAS-102 whether: 1. Intestinal microbiota composition can act as a predictor for response. 2. Intestinal microbiota composition changes during systemic treatment and its relation to chemotoxicity. BACKGROUND: Gut microbiota and host determinants evolve in symbiotic and dependent relationships resulting in a personal ecosystem...
April 25, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28439715/carcinoembryonic-antigen-testing-after-curative-liver-resection-for-synchronous-liver-metastasis-of-colorectal-cancer-a-japanese-multicenter-analysis
#10
Satoshi Okazaki, Hironobu Baba, Noriko Iwata, Shinichi Yamauchi, Kenichi Sugihara
PURPOSE: To identify the possible roles of carcinoembryonic antigen (CEA) testing after liver resection for synchronous colorectal liver metastasis (CLM). METHODS: The subjects of this retrospective study were patients who underwent complete resection of primary tumors and synchronous CLM between 1997 and 2007 at 20 institutions in Japan. We studied the associations between perioperative CEA levels and the characteristics of recurrence. RESULTS: Recurrence was detected during the median follow-up time of 52 months in 445 (73...
April 24, 2017: Surgery Today
https://www.readbyqxmd.com/read/28437692/stage-iv-colorectal-cancer-primary-site-and-patterns-of-distant-metastasis
#11
Jamaica R Robinson, Polly A Newcomb, Sheetal Hardikar, Stacey A Cohen, Amanda I Phipps
BACKGROUND: Although colorectal cancer (CRC) usually metastasizes to the liver and/or lungs, factors influencing the anatomic pattern of metastases remain poorly understood. METHODS: We assessed the relationship between primary CRC site and pattern of synchronous metastasis among 1202 individuals diagnosed with incident metastatic CRC between 2010 and 2014 and identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) registry...
April 21, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28435294/patient-considerations-in-metastatic-colorectal-cancer-role-of-panitumumab
#12
REVIEW
Jane E Rogers
Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies, including colorectal cancer (CRC), making EGFR an attractive treatment option. Panitumumab and cetuximab, monoclonal antibodies (mAbs) directed at EGFR, are both currently utilized in the management of metastatic CRC (mCRC). Through the development of these agents in mCRC, key issues surrounding each mAbs use have been revealed. These key issues include negative patient outcome avoidance when determining use, the economic burden with high-cost medication, predictive biomarkers, tumor location, patient geographic location, patient quality of life, and the prevention of debilitating adverse effects...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28433602/folfoxiri-regimen-for-metastatic-colorectal-cancer-a-systematic-review-and-meta-analysis
#13
Frederico Leal, Fernanda Proa Ferreira, Andre Deeke Sasse
INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases...
March 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28433601/volumetric-versus-unidimensional-measures-of-metastatic-colorectal-cancer-in-assessing-disease-response
#14
Meghan G Lubner, Nicholas Stabo, Sam J Lubner, Alejandro Munoz Del Rio, Chihwa Song, Perry J Pickhardt
INTRODUCTION: The purpose of this study was to compare unidimensional (1D/linear) and volumetric (3D) measures of metastatic colorectal cancer (mCRC) at computed tomography (CT) for predicting clinical outcome. PATIENTS AND METHODS: Analysis of CT images in 105 patients (mean age, 59 years; range, 25-81 years; 45 women, 60 men) receiving treatment for mCRC was performed. Both unidimensional and volumetric measures were obtained on index lesions at 3 time points (baseline/midpoint/post-therapy; mean interval, 4...
March 27, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28432610/left-versus-right-does-location-matter-for-refractory-metastatic-colorectal-cancer-patients-in-phase-1-clinical-trials
#15
Sukeshi Patel Arora, Norma S Ketchum, Joel Michalek, Jonathon Gelfond, Devalingam Mahalingam
PURPOSE: Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies. METHODS: A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012...
April 22, 2017: Journal of Gastrointestinal Cancer
https://www.readbyqxmd.com/read/28431527/evaluation-of-the-correlation-of-vasculogenic-mimicry-aldh1-kai1-and-microvessel-density-in-the-prediction-of-metastasis-and-prognosis-in-colorectal-carcinoma
#16
Bo Zhu, Lei Zhou, Lan Yu, Shiwu Wu, Wenqing Song, Xiaomeng Gong, Danna Wang
BACKGROUND: Metastasis and recurrence are the most common reasons for treatment failure of colorectal carcinoma (CRC). Vasculogenic mimicry (VM, blood supply formation often seen in highly aggressive tumors), Aldehyde dehydrogenase 1 (ALDH1, a biomarker of cancer stem cells), KAI1 (a suppressor gene of tumor metastasis) are all valuable factors for metastasis and prognosis in diverse human cancers. However, the correlation of VM, ALDH1, KAI1 and microvessel density (MVD) in CRC is unclear...
April 21, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#17
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28430862/how-health-related-quality-of-life-assessment-should-be-used-in-advanced-colorectal-cancer-clinical-trials
#18
F Bonnetain, C Borg, R R Adams, J A Ajani, A Benson, H Bleiberg, B Chibaudel, E Diaz-Rubio, J Y Douillard, C S Fuchs, B J Giantonio, R Goldberg, V Heinemann, M Koopman, R Labianca, A K Larsen, T Maughan, E Mitchell, M Peeters, C J A Punt, H J Schmoll, C Tournigand, A de Gramont
Traditionally, the efficacy of cancer treatment in patients with advance or metastatic disease in clinical studies has been studied using overall survival (OS) and more recently tumor-based endpoints such as progression-free survival, measurements of response to treatment. However, these seem not to be the relevant clinical endpoints in current situation if such endpoints were no validated as surrogate of OS to demonstrate the clinical efficacy. Appropriate, meaningful, primary patient-oriented and patient-reported endpoints that adequately measure the effects of new therapeutic interventions are then crucial for the advancement of clinical research in metastatic colorectal cancer to complement the results of tumor-based endpoints...
April 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28430643/lymph-node-status-as-a-prognostic-factor-after-palliative-resection-of-primary-tumor-for-patients-with-metastatic-colorectal-cancer
#19
Qingguo Li, Changjian Wang, Yaqi Li, Xinxiang Li, Ye Xu, Guoxiang Cai, Peng Lian, Sanjun Cai
Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430582/lncrna-chrf-induced-mir-489-loss-promotes-metastasis-of-colorectal-cancer-via-twist1-emt-signaling-pathway
#20
Youmao Tao, Tao Han, Tao Zhang, Chong Ma, Caixia Sun
microRNA-489 (miR-489) is a novel cancer-related miRNAs and functions as a tumor suppressor in human cancers. While, the clinical significance of miR-489 and its role in colorectal cancer (CRC) remain rarely known. Here, we found that the levels of miR-489 in CRC tissues were significantly lower than those in matched tumor-adjacent tissues. Furthermore, decreased levels of miR-489 also observed in CRC cell lines compared to HIEC cells. Clinicopathological analysis revealed that miR-489 underexpression was positively correlated with advanced pT stage, pN stage and AJCC stage...
April 5, 2017: Oncotarget
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