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Metastatic colorectal cancer

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https://www.readbyqxmd.com/read/28654634/emergence-of-met-hyper-amplification-at-progression-to-met-and-braf-inhibition-in-colorectal-cancer
#1
Daniele Oddo, Giulia Siravegna, Annunziata Gloghini, Claudio Vernieri, Benedetta Mussolin, Federica Morano, Giovanni Crisafulli, Rosa Berenato, Giorgio Corti, Chiara Costanza Volpi, Michela Buscarino, Monica Niger, Philip D Dunne, Giuseppe Rospo, Emanuele Valtorta, Alice Bartolini, Giovanni Fucà, Simona Lamba, Antonia Martinetti, Maria Di Bartolomeo, Filippo de Braud, Alberto Bardelli, Filippo Pietrantonio, Federica Di Nicolantonio
BACKGROUND: Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF(V600E) and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown. METHODS: We analysed plasma circulating tumour DNA obtained at progression by exome sequencing and digital PCR. MET gene and mRNA in situ hybridisation analyses in two bioptic specimens obtained at progression were used to confirm the plasma data...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28654140/epidermal-growth-factor-receptor-egfr-inhibitors-for-metastatic-colorectal-cancer
#2
REVIEW
David Lok Hang Chan, Eva Segelov, Rachel Sh Wong, Annabel Smith, Rebecca A Herbertson, Bob T Li, Niall Tebbutt, Timothy Price, Nick Pavlakis
BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors prevent cell growth and have shown benefit in the treatment of metastatic colorectal cancer, whether used as single agents or in combination with chemotherapy. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). However, there is ongoing debate as to which patient populations gain maximum benefit from EGFR inhibition and where they should be used in the metastatic colorectal cancer treatment paradigm to maximise efficacy and minimise toxicity...
June 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28653974/hla-g-3-utr-polymorphisms-predict-drug-induced-g3-4-toxicity-related-to-folinic-acid-5-fluorouracil-oxaliplatin-folfox4-chemotherapy-in-non-metastatic-colorectal-cancer
#3
Marica Garziera, Saverio Virdone, Elena De Mattia, Lucia Scarabel, Erika Cecchin, Jerry Polesel, Mario D'Andrea, Nicoletta Pella, Angela Buonadonna, Adolfo Favaretto, Giuseppe Toffoli
Polymorphisms in drug-metabolizing enzymes might not completely explain inter-individual differences in toxicity profiles of patients with colorectal cancer (CRC) that receive folinic acid/5-fluorouracil/oxaliplatin (FOLFOX4). Recent data indicate that the immune system could contribute to FOLFOX4 outcomes. In light of the immune inhibitory nature of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, we aimed to identify novel genomic markers of grades 3 and 4 (G3-4) toxicity related to FOLFOX4 therapy in patients with CRC...
June 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28653815/factors-associated-with-the-development-and-severity-of-oxaliplatin-induced-peripheral-neuropathy-a-systematic-review
#4
REVIEW
Jeremy N Pulvers, Gavin Marx
Oxaliplatin is a platinum-derivative chemotherapeutic agent used for colorectal cancer in the adjuvant and metastatic setting in combination with folinic acid and 5-fluorouracil. Oxaliplatin causes an acute cold-induced neurotoxicity and a chronic cumulative neuropathy, which can require dose modification and impact quality of life. To date, no prevention and treatment strategies have proved effective thus reinforcing the importance of identifying at-risk patients in order to maximize therapeutic benefit while minimizing neurotoxicity...
June 27, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28653161/the-post-sir-spheres-surgery-study-p4s-retrospective-analysis-of-safety-following-hepatic-resection-or-transplantation-in-patients-previously-treated-with-selective-internal-radiation-therapy-with-yttrium-90-resin-microspheres
#5
Fernando Pardo, Bruno Sangro, Rheun-Chuan Lee, Derek Manas, Rohan Jeyarajah, Vincent Donckier, Geert Maleux, Antonio D Pinna, Lourens Bester, David L Morris, David Iannitti, Pierce K Chow, Richard Stubbs, Paul J Gow, Gianluca Masi, Kevin T Fisher, Wan Y Lau, Konstantinos Kouladouros, Georgios Katsanos, Giorgio Ercolani, Fernando Rotellar, José I Bilbao, Michael Schoen
BACKGROUND: Reports show that selective internal radiation therapy (SIRT) may downsize inoperable liver tumors to resection or transplantation, or enable a bridge-to-transplant. A small-cohort study found that long-term survival in patients undergoing resection following SIRT appears possible but no robust studies on postsurgical safety outcomes exist. The Post-SIR-Spheres Surgery Study was an international, multicenter, retrospective study to assess safety outcomes of liver resection or transplantation following SIRT with yttrium-90 (Y-90) resin microspheres (SIR-Spheres(®); Sirtex)...
June 26, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28652998/association-of-primary-tumor-lymph-node-ratio-with-burden-of-liver-metastases-and-survival-in-stage-iv-colorectal-cancer
#6
Ali Ahmad, Jeffrey Reha, Abdul Saied, N Joseph Espat, Ponnandai Somasundar, Steven C Katz
BACKGROUND: The primary objective of our study was to assess the association of primary tumor lymph node ratio (LNR) in stage IV colorectal adenocarcinomas (CRC) with overall survival (OS) and the extent of metastatic disease in the liver. METHODS: We analyzed data on 53 stage IV CRC patients who underwent surgical resection of the primary tumor. The median LNR of 0.25 was used to stratify patients into high LNR (H-LNR) and low LNR (L-LNR) groups. Statistical comparison was performed using chi square test and multiple regression models...
June 2017: Hepatobiliary Surgery and Nutrition
https://www.readbyqxmd.com/read/28651746/the-management-of-colorectal-liver-metastases
#7
B Maher, E Ryan, M Little, P Boardman, B Stedman
Colorectal cancer remains a leading cause of cancer-related death in Europe. Approximately one-quarter of patients have synchronous hepatic metastases and metachronous liver metastases occur in a further 30%. The scope of surgery in management of colorectal metastases has evolved to include selected patients with extra-hepatic disease for whom R0 resection is considered feasible; however, locoregional treatments are increasingly recognised as viable management options in those patients deemed unsuitable for surgery and there is an expanding body of evidence regarding their ability to achieve local control and increase progression-free survival in the liver...
June 23, 2017: Clinical Radiology
https://www.readbyqxmd.com/read/28649886/epidermal-growth-factor-inhibitors-in-first-line-for-metastatic-colorectal-cancer-with-ras-wild-type-a-perspective-based-on-pharmacological-costs
#8
Jacopo Giuliani, Andrea Bonetti
In light of the relevant expenses of pharmacological interventions it might be interesting to make a balance between the cost of the new drugs administered, such as EGFRIs (cetuximab and panitunumab) and the added value represented by the improvement of the clinical parameters of interest such as progression free survival (PFS). Areas Covered: The analysis was conducted to assess the effect of front-line chemotherapy on the PFS, separately, on each arm of the evaluated trials. Only phase III randomized controlled trials (RCTs) were considered...
June 24, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28649871/the-potential-role-of-nintedanib-in-treating-colorectal-cancer
#9
Antonio Rossi, Tiziana Pia Latiano, Paola Parente, Cinzia Chiarazzo, Filomena Limosani, Gabriele Di Maggio, Evaristo Maiello
Angiogenesis leads to the growth, progression, and metastases of a variety of solid tumors, including metastatic colorectal cancer (mCRC), involving particularly the family of vascular endothelial growth factors (VEGF) and their receptors (VEGFR). Several anti-angiogenic inhibitors are already registered for mCRC therapy: bevacizumab, aflibercept, ramucirumab, regorafenib. Nintedanib is a new triple angiokinase oral inhibitor that potently blocks the proangiogenic pathways mediated by VEGFR, platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR)...
June 26, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28645859/discovery-of-a-novel-pan-raf-inhibitor-with-potent-anti-tumor-activity-in-preclinical-models-of-braf-v600e-mutant-cancer
#10
Sung Pyo Hong, Soon Kil Ahn
AIMS: BRAF mutations, especially BRAF V600E, are a frequent occurrence in malignant melanomas. The BRAF inhibitors are used as the care standard for BRAF-mutant metastatic melanomas. However, melanomas rapidly develop resistance to BRAF inhibitors after a median response duration of 6months, and the subsequent rapid development of cutaneous toxicity is enhanced by the paradoxical activation of CRAF. In this study, we discovered a potent and selective pan-RAF inhibitor: INU-152. The goal of this study was to investigate whether the inhibition of pan-RAF with INU-152 completely disrupts the MAPK pathway in cancer cells bearing BRAF or RAS mutations...
June 20, 2017: Life Sciences
https://www.readbyqxmd.com/read/28645720/direct-circulating-tumor-dna-detection-from-unpurified-plasma-using-a-digital-pcr-platform
#11
David Sefrioui, Ludivine Beaussire, Anne Perdrix, Florian Clatot, Pierre Michel, Thierry Frebourg, Frédéric Di Fiore, Nasrin Sarafan-Vasseur
BACKGROUND: In standard pre-analytical conditions, an isolation step is required for circulating tumor DNA (ctDNA) analysis. The need for this step remains unclear with the development of ultrasensitive detection technologies such as digital PCR (dPCR). The aim of our study was to evaluate the ctDNA detection by dPCR platform either directly from plasma (plasma group, PG) or after an isolation step (isolation group, IG). METHODS: We included 17 patients corresponding to a selection of 43 blood samples in metastatic colorectal cancer patients...
June 20, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28644426/the-association-between-the-serum-levels-of-matrix-metalloproteinase-9-and-colorectal-cancer
#12
Ismar Rašić, Azra Rašić, Goran Akšamija, Svjetlana Radović, Nedžad Šehović
Aim To determine the serum levels of matrix metalloproteinase 9 (MMP-9) concentration and their association with the stage and histopathologic sizes of colorectal cancer (CRC). Methods One hundred and two patients with clinically diagnosed and histologically confirmed colorectal cancer ready for surgical treatment were included in the study. In each patient, preoperative peripheral venous blood samples were taken for determination of the concentration of MMP-9 using ELISA immunoassay test. Resected tumour specimens were studied pathologically according to the criteria of the TNM classification...
August 1, 2017: Medicinski Glasnik
https://www.readbyqxmd.com/read/28643862/tumor-angiogenesis-revisited-regulators-and-clinical-implications
#13
REVIEW
Roberto Ronca, Mohammed Benkheil, Stefania Mitola, Sofie Struyf, Sandra Liekens
Since Judah Folkman hypothesized in 1971 that angiogenesis is required for solid tumor growth, numerous studies have been conducted to unravel the angiogenesis process, analyze its role in primary tumor growth, metastasis and angiogenic diseases, and to develop inhibitors of proangiogenic factors. These studies have led in 2004 to the approval of the first antiangiogenic agent (bevacizumab, a humanized antibody targeting vascular endothelial growth factor) for the treatment of patients with metastatic colorectal cancer...
June 23, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28643319/-progress-of-the-application-of-optical-coherence-tomography-in-gastrointestinal-tumor-surgery
#14
Yongsheng Li, Hao Liu, Haipeng Huang, Yu Zhu, Haijun Deng, Jiang Yu, Site Luo, Li Huo, Li Lin, Huikai Xie, Guoxin Li
Optical coherence tomography (OCT) is a real-time, cross-sectional optical imaging technology. It is analogous to ultrasonography, except that OCT uses light waves instead of sound waves, and can provide three-dimensional morphological images of living tissues with a micrometer resolution. Through the use of endoscopes, needles, catheters and laparoscopes, OCT has demonstrated tremendous imaging potential in tumor surgery. The current studies suggest that OCT has potential for clinical applications in the following fields of gastrointestinal tumor surgery: (1) Early tumor detection and diagnosis: OCT can distinguish differences between polyp tissue, normal tissue and malignant tissue...
June 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28643310/-establishment-of-a-prognostic-nomogram-to-predict-long-term-survival-in-non-metastatic-colorectal-cancer-patients
#15
Xiaojie Wang, Pan Chi, Huiming Lin, Xingrong Lu, Ying Huang, Zongbin Xu, Shenghui Huang, Yanwu Sun, Daoxiong Ye
OBJECTIVE: To establish a nomogram to predict long-term survival in non-metastatic colorectal cancer patients. METHODS: A retrospective analysis was conducted in patients with non-metastatic colorectal cancer who underwent radical surgery in the Department of Colorectal Surgery of Affiliated Union Hospital of Fujian Medical University between January 2000 and December 2014. Univariate and multivariate analyses on disease-free survival (DFS) were performed using the Cox proportional regression model...
June 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28641703/a-randomised-controlled-trial-to-assess-the-cost-effectiveness-of-intensive-versus-no-scheduled-follow-up-in-patients-who-have-undergone-resection-for-colorectal-cancer-with-curative-intent
#16
David Mant, Alastair Gray, Siân Pugh, Helen Campbell, Stephen George, Alice Fuller, Bethany Shinkins, Andrea Corkhill, Jane Mellor, Elizabeth Dixon, Louisa Little, Rafael Perera-Salazar, John Primrose
BACKGROUND: Intensive follow-up after surgery for colorectal cancer is common practice but lacks a firm evidence base. OBJECTIVE: To assess whether or not augmenting symptomatic follow-up in primary care with two intensive methods of follow-up [monitoring of blood carcinoembryonic antigen (CEA) levels and scheduled imaging] is effective and cost-effective in detecting the recurrence of colorectal cancer treatable surgically with curative intent. DESIGN: Randomised controlled open-label trial...
May 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28641461/the-impact-of-data-errors-on-the-outcome-of-randomized-clinical-trials
#17
Marc Buyse, Pierre Squifflet, Elisabeth Coart, Emmanuel Quinaux, Cornelis Ja Punt, Everardo D Saad
Background/aims Considerable human and financial resources are typically spent to ensure that data collected for clinical trials are free from errors. We investigated the impact of random and systematic errors on the outcome of randomized clinical trials. Methods We used individual patient data relating to response endpoints of interest in two published randomized clinical trials, one in ophthalmology and one in oncology. These randomized clinical trials enrolled 1186 patients with age-related macular degeneration and 736 patients with metastatic colorectal cancer...
June 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/28640257/tumor-suppressive-mir-26a-and-mir-26b-inhibit-cell-aggressiveness-by-regulating-fut4-in-colorectal-cancer
#18
Yang Li, Zheng Sun, Bing Liu, Yujia Shan, Lifen Zhao, Li Jia
Metastasis is a multistep molecular network process, which is the major cause of death in patients with colorectal cancer (CRC). MicroRNAs (miRNAs) play pivotal roles in tumorigenesis as either tumor suppressors or oncogenes. Increased expression of fucosyltransferase4 (FUT4) has been reported to be associated with the invasive and metastatic properties of CRC. Here to identify potential key miRNAs and their target genes for colorectal cancer (CRC), we compared miRNA expression profiles between metastatic CRC cell SW620 and primary CRC cell SW480...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28639044/short-term-surgical-outcomes-of-minimally-invasive-repeat-hepatectomy-for-recurrent-liver-cancer
#19
Takehiro Noda, Hidetoshi Eguchi, Hiroshi Wada, Yoshifumi Iwagami, Daisaku Yamada, Tadafumi Asaoka, Kunihito Gotoh, Koichi Kawamoto, Yutaka Takeda, Masahiro Tanemura, Koji Umeshita, Yuichiro Doki, Masaki Mori
BACKGROUND: Repeat liver resection is an effective treatment, with long-term surgical outcomes for recurrent hepatocellular carcinoma and colorectal liver metastasis. However, the efficacy of a minimally invasive surgical approach for recurrent liver cancer is not yet confirmed. The purpose of this study is to examine the efficacy of minimally invasive repeat liver resection (MISRLR) compared with open repeat liver resection (ORLR) for primary and metastatic liver cancer. Here, we retrospectively analyzed the clinicopathological features and short-term surgical outcomes of patients undergoing MISRLR and ORLR...
June 21, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28638476/therapeutic-inhibition-of-mir-4260-suppresses-colorectal-cancer-via-targeting-mcc-and-smad4
#20
Junjie Xiao, Dongchao Lv, Jinzhe Zhou, Yihua Bei, Ting Chen, Muren Hu, Qiulian Zhou, Siyi Fu, Qi Huang
Dysregulation of microRNAs (miRNAs, miRs) and their putative target genes have been increasingly reported to contribute to colorectal cancer. However, miRNAs that directly target the mutated in colorectal cancer (MCC) gene, a tumor suppressor which is downregulated or inactivated in colorectal cancer, remain largely unknown. By using an array-based miRNA analysis, we identified a group of miRNAs that were dysregulated in human metastatic versus non-metastatic colorectal cancer tissues. One of these miRNAs, miR-4260, was predicted to target MCC in the miRDB database...
2017: Theranostics
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