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Metastatic colorectal cancer

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https://www.readbyqxmd.com/read/29353165/prognostic-value-of-primary-tumour-resection-in-synchronous-metastatic-colorectal-cancer-individual-patient-data-analysis-of-first-line-randomised-trials-from-the-arcad-database
#1
K L van Rooijen, Q Shi, K K H Goey, J Meyers, V Heinemann, E Diaz-Rubio, E Aranda, A Falcone, E Green, A de Gramont, D J Sargent, C J A Punt, M Koopman
Indication for primary tumour resection (PTR) in asymptomatic metastatic colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses suggest a survival benefit for patients who underwent PTR. The aim was to evaluate the prognostic value of PTR in patients with synchronous mCRC by analysis of recent large RCTs including systemic therapy with modern targeted agents. Individual patient data (IPD) of 3423 patients enrolled into 8 randomised controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analysed...
January 17, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29352441/utility-of-tumor-burden-score-to-stratify-prognosis-of-patients-with-hepatocellular-cancer-results-of-4759-cases-from-ita-li-ca-study-group
#2
Alessandro Vitale, Quirino Lai, Fabio Farinati, Laura Bucci, Edoardo G Giannini, Lucia Napoli, Francesca Ciccarese, Gian Lodovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Rodolfo Sacco, Giuseppe Cabibbo, Roberto Virdone, Fabio Marra, Martina Felder, Filomena Morisco, Luisa Benvegnù, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Gabriele Missale, Alberto Masotto, Gerardo Nardone, Antonio Colecchia, Mauro Bernardi, Franco Trevisani, Timothy M Pawlik
BACKGROUND: Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population...
January 19, 2018: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/29352327/limk-cofilin-pathway-and-slingshot-are-implicated-in-human-colorectal-cancer-progression-and-chemoresistance
#3
Helen Aggelou, Panagiota Chadla, Sofia Nikou, Sofia Karteri, Ioannis Maroulis, Haralabos P Kalofonos, Helen Papadaki, Vasiliki Bravou
Cofilin phospho-regulation is important for actin filament turnover and is implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH promote cancer cell invasion and metastasis and represent novel anti-cancer targets. However, little is known regarding LIMK/cofilin and SSH in human colorectal cancer (CRC). In this study, we aimed to address their expression and significance in human CRC. We evaluated expression of non-phosphorylated (active) and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143 human CRC samples in relation to clinicopathologic parameters, response of metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT) markers β-catenin, E-cadherin, and ZEB...
January 19, 2018: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29351242/-vessels-in-the-storm-searching-for-prognostic-and-predictive-angiogenic-factors-in-colorectal-cancer
#4
REVIEW
Adriano Angelucci, Simona Delle Monache, Alessio Cortellini, Monica Di Padova, Ficorella Corrado
High expectations are placed upon anti-angiogenic compounds for metastatic colorectal cancer (mCRC), the first malignancy for which such type of treatment has been approved. Indeed, clinical trials have confirmed that targeting the formation of new vessels can improve in many cases clinical outcomes of mCRC patients. However, current anti-angiogenic drugs are far from obtaining the desirable or expected curative results. Many are the factors probably involved in such disappointing results, but particular attention is currently focused on the validation of biomarkers able to improve the direction of treatment protocols...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29348907/microsatellite-stability-and-mismatch-repair-proficiency-in-nasopharyngeal-carcinoma-may-not-predict-programmed-death-1-blockade-resistance
#5
Xiyi Liao, Liang Zhao, Sangang Wu, Hua Zheng, Haojun Chen, Huan Zhang, ZiJing Wang, Qin Lin
The US FDA granted accelerated approval to pembrolizumab for microsatellite instability-high and mismatch repair deficient cancers. The response of programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal cancer is very poor, however, whether such treatment is effective in pMMR nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29346573/the-addition-of-bevacizumab-to-oxaliplatin-based-chemotherapy-impact-upon-hepatic-sinusoidal-injury-and-thrombocytopenia
#6
Michael J Overman, Renata Ferrarotto, Kanwal Raghav, Binsah George, Wei Qiao, Karime K Machado, Leonard B Saltz, Thibault Mazard, J N Vauthey, Paulo M Hoff, Brian Hobbs, Evelyn M Loyer, Scott Kopetz
Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. Evidence suggests that bevacizumab may protect against HSI. Methods: Two cohorts of metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory cohort of 184 patients treated at a single institution from 2003 to 2010 and a confirmatory cohort of 200 patients from a multi-institutional randomized trial (NO16966)...
January 15, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29346040/bevacizumab-maintenance-versus-no-maintenance-during-chemotherapy-free-intervals-in-metastatic-colorectal-cancer-a-randomized-phase-iii-trial-prodige-9
#7
Thomas Aparicio, Francois Ghiringhelli, Valérie Boige, Karine Le Malicot, Julien Taieb, Olivier Bouché, Jean-Marc Phelip, Eric François, Christian Borel, Roger Faroux, Laetitia Dahan, Stéphane Jacquot, Dominique Genet, Faiza Khemissa, Etienne Suc, Françoise Desseigne, Patrick Texereau, Come Lepage, Jaafar Bennouna
Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI...
January 18, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29345521/development-and-validation-of-an-elisa-to-study-panitumumab-pharmacokinetics
#8
Céline Desvignes, Christophe Passot, David Ternant, Morgane Caulet, Caroline Guérineau, Thierry Lecomte, Gilles Paintaud
AIM: Panitumumab is a monoclonal antibody directed against EGFR that is approved for the treatment of metastatic colorectal cancer. To investigate its pharmacokinetics and concentration-response relationship, a validated assay is required. RESULTS: An ELISA assay was developed and validated according to international recommendations. Six calibrators (ranging from 0.1 to 20 mg/l) plus one anchor point (50 mg/l) and three quality controls (0.45, 2 and 8 mg/l) were defined...
January 18, 2018: Bioanalysis
https://www.readbyqxmd.com/read/29344789/laparoscopic-conversion-in-colorectal-cancer-surgery-is-there-any-improvement-over-time-at-a-population-level
#9
Michael P M de Neree Tot Babberich, Julia T van Groningen, Evelien Dekker, Theo Wiggers, Michel W J M Wouters, Willem A Bemelman, Pieter J Tanis
Conversion of laparoscopic colorectal cancer resection has been associated with worse outcome, but this might have been related to a learning curve effect. This study aimed to evaluate incidence, predictive factors and outcomes of laparoscopic conversion after the implementation phase of laparoscopic surgery at a population level. Patients undergoing elective resection of non-locally advanced, non-metastatic colorectal cancer between 2011 and 2015 were included. Data were extracted from the Dutch Surgical Colorectal Audit...
January 17, 2018: Surgical Endoscopy
https://www.readbyqxmd.com/read/29344282/clinical-significance-of-glycoprotein-non-metastatic-b-and-its-association-with-egfr-her2-in-gastrointestinal-cancer
#10
Jesse Yu Tajima, Manabu Futamura, Siqin Gaowa, Ryutaro Mori, Toshiyuki Tanahashi, Yoshihiro Tanaka, Nobuhisa Matsuhashi, Takao Takahashi, Kazuya Yamaguchi, Tatsuhiko Miyazaki, Kazuhiro Yoshida
Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and motility. We previously reported cross-talk between GPNMB and human epidermal growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might play an important role in resistance to anti-HER2 therapy in breast cancer. Here, we clarified the association between GPNMB and HER-family proteins in gastrointestinal cancer by examining their relationships using gastric and colorectal cancer cell lines...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344222/herbal-compound-teng-long-bu-zhong-tang-inhibits-metastasis-in-human-rko-colon-carcinoma
#11
Meng-Meng Wei, Shuang-Shuang Wang, Jia-Lu Zheng, Jin-Jun Chen, Xia Yan, Hong-Mei An, Bing Hu
Metastasis is one of the primary obstacles to the successful treatment of colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal formula that may be useful in the treatment of metastatic colorectal cancer. The present study evaluated the effects of TLBZT on lung metastasis in human RKO colon carcinoma cells injected into mice via the tail vein. The results demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia-inducible factor 1α...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343971/assessment-of-the-cardiac-safety-between-cetuximab-and-panitumumab-as-single-therapy-in-chinese-chemotherapy-refractory-mcrc
#12
Xue-Miao Tang, Hao Chen, Qing Li, Yiling Song, Shuping Zhang, Xiao-Shuan Xu, Yiwei Xu, Shulin Chen
Objective: The cardiac safety of cetuximab and panitumumab, particularly as single agents, has not been investigated extensively. This trial was designed to specifically evaluate the cardiac safety of cetuximab and panitumumab as single therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. Patients and methods: Sixty-one patients received cetuximab at an initial dose of 400 mg/m2 intravenously over 120 minutes on day 1 (week 1), followed by a maintenance dose of 250 mg/m2 intravenously over 60 minutes on day 1 of each 7-day cycle...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29342159/prediction-of-novel-target-genes-and-pathways-involved-in-bevacizumab-resistant-colorectal-cancer
#13
Precious Takondwa Makondi, Chia-Hwa Lee, Chien-Yu Huang, Chi-Ming Chu, Yu-Jia Chang, Po-Li Wei
Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs)...
2018: PloS One
https://www.readbyqxmd.com/read/29341150/effect-of-akt-activation-and-experimental-pharmacological-inhibition-on-responses-to-neoadjuvant-chemoradiotherapy-in-rectal-cancer
#14
F C Koyama, C M Lopes Ramos, F Ledesma, V A F Alves, J M Fernandes, B B Vailati, G P São Julião, A Habr-Gama, J Gama-Rodrigues, R O Perez, A A Camargo
BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT. METHODS: Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal verge...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29341112/conditionally-reprogrammed-cells-crc-methodology-does-not-allow-the-in-vitro-expansion-of-patient-derived-primary-and-metastatic-lung-cancer-cells
#15
Giovanni Sette, Valentina Salvati, Ilenia Giordani, Emanuela Pillozzi, Denise Quacquarini, Enrico Duranti, Francesca De Nicola, Matteo Pallocca, Maurizio Fanciulli, Mario Falchi, Roberto Pallini, Ruggero De Maria, Adriana Eramo
Availability of tumor and non-tumor patient-derived models would promote the development of more effective therapeutics for Non Small Cell Lung Cancer (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology demonstrated exceptional potential for the expansion of epithelial cells from patient tissues. However, the possibility to expand patient-derived lung cancer cells using CRC protocols is controversial. Here, we used CRC approach to expand cells from non-tumoral and tumor biopsies of patients with primary or metastatic NSCLC as well as pulmonary metastases of colorectal or breast cancers...
January 17, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29338703/diagnostic-accuracy-and-prediction-increment-of-markers-of-epithelial-mesenchymal-transition-to-assess-cancer-cell-detachment-from-primary-tumors
#16
Evan L Busch, Prabhani Kuruppumullage Don, Haitao Chu, David B Richardson, Temitope O Keku, David A Eberhard, Christy L Avery, Robert S Sandler
BACKGROUND: Metastases play a role in about 90% of cancer deaths. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells might provide diagnostic information about the likelihood that cancer cells have detached from the primary tumor. Used together with established diagnostic tests of detachment-lymph node evaluation and radiologic imaging-EMT marker measurements might improve the ability of clinicians to assess the patient's risk of metastatic disease...
January 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29338550/the-role-of-tumor-angiogenesis-as-a-therapeutic-target-in-colorectal-cancer
#17
Francesca Battaglin, Alberto Puccini, Rossana Intini, Marta Schirripa, Alessandra Ferro, Francesca Bergamo, Sara Lonardi, Vittorina Zagonel, Heinz-Josef Lenz, Fotios Loupakis
Angiogenesis is a complex process regulated by several pro- and anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role in colorectal cancer (CRC) development and progression. Therapeutic agents targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be effective across different treatment lines in metastatic CRC (mCRC) and contributed greatly to improve patients' survival in recent years. Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives...
January 17, 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29337243/intratumoral-morphological-heterogeneity-can-be-an-indicator-of-genetic-heterogeneity-in-colorectal-cancer
#18
Juliane Büttner, Korinna Jöhrens, Frederick Klauschen, Michael Hummel, Dido Lenze, Wolfgang Saeger, Annika Lehmann
Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with RAS wild-type. However, resistance to targeted therapy is often observed and can be primary or acquired. One reason for primary resistance is the presence of mutations that are undetected due to genetic heterogeneity, which can be expressed by differences present in primary tumor and distant metastasis or recurrence or by an intratumoral heterogeneity (presence of different subclones in the investigated tumor sample). The aim of our study was to investigate if morphological heterogeneity can be an indicator of intratumoral heterogeneity...
January 11, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29335811/surgical-stress-response-and-promotion-of-metastasis-in-colorectal-cancer-a-complex-and-heterogeneous-process
#19
Corina Behrenbruch, Carolyn Shembrey, Sophie Paquet-Fifield, Christina Mølck, Hyun-Jung Cho, Michael Michael, Benjamin N J Thomson, Alexander G Heriot, Frédéric Hollande
Surgery remains the curative treatment modality for colorectal cancer in all stages, including stage IV with resectable liver metastasis. There is emerging evidence that the stress response caused by surgery as well as other perioperative therapies such as anesthesia and analgesia may promote growth of pre-existing micro-metastasis or potentially initiate tumor dissemination. Therapeutically targeting the perioperative period may therefore reduce the effect that surgical treatments have in promoting metastases, for example by combining β-adrenergic receptor antagonists and cyclooxygenase-2 (COX-2) inhibitors in the perioperative setting...
January 15, 2018: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/29334918/colorectal-cancer-liver-metastases-a-population-based-study-on-incidence-management-and-survival
#20
Jennie Engstrand, Henrik Nilsson, Cecilia Strömberg, Eduard Jonas, Jacob Freedman
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-associated deaths with liver metastases developing in 25-30% of those affected. Previous data suggest a survival difference between right- and left-sided liver metastatic CRC, even though left-sided cancer has a higher incidence of liver metastases. The aim of the study was to describe the liver metastatic patterns and survival as a function of the characteristics of the primary tumour and different combinations of metastatic disease...
January 15, 2018: BMC Cancer
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