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https://www.readbyqxmd.com/read/28640830/optimal-sequencing-strategies-for-identifying-disease-associated-singletons
#1
Sara Rashkin, Goo Jun, Sai Chen, Goncalo R Abecasis
With the increasing focus of genetic association on the identification of trait-associated rare variants through sequencing, it is important to identify the most cost-effective sequencing strategies for these studies. Deep sequencing will accurately detect and genotype the most rare variants per individual, but may limit sample size. Low pass sequencing will miss some variants in each individual but has been shown to provide a cost-effective alternative for studies of common variants. Here, we investigate the impact of sequencing depth on studies of rare variants, focusing on singletons-the variants that are sampled in a single individual and are hardest to detect at low sequencing depths...
June 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636562/exosome-encapsulated-micrornas-as-circulating-biomarkers-for-colorectal-cancer
#2
Shushan Yan, Bing Han, Shunyuan Gao, Xiaochen Wang, Zengfang Wang, Fakai Wang, Jianjun Zhang, Donghua Xu, Beicheng Sun
Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#3
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636427/liver-directed-therapy-in-metastatic-colorectal-cancer
#4
Ciara M Kelly, Nancy E Kemeny
Colorectal cancer is a significant global health issue with over 1 million cases diagnosed annually throughout the world. 15% of patients diagnosed with colorectal cancer will have liver metastases and 60% will develop liver metastases if they have metastatic disease. Oligometastatic colorectal cancer confined to the liver represents an intermediate state in the evolution of metastatic capacity that opens the opportunity for local interventions. Area's covered: The literature supports long-term survival if patients undergo liver resection of colorectal metastases...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28634730/phase-iii-trial-comparing-uft%C3%A2-%C3%A2-psk-to-uft%C3%A2-%C3%A2-lv-in-stage-iib-iii-colorectal-cancer-mcsgo-cctg
#5
Yasuhiro Miyake, Junichi Nishimura, Takeshi Kato, Masataka Ikeda, Masaki Tsujie, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Mitsugu Sekimoto, Riichiro Nezu, Yuichiro Doki, Masaki Mori
PURPOSE: Oral adjuvant uracil and tegafur plus leucovorin (UFT/LV) is not inferior to standard weekly fluorouracil and folinate for stage II/III colon cancer. However, protein-bound polysaccharide K (PSK) has been evaluated as postoperative adjuvant therapy for colorectal cancer. This report is the first of MCSGO-CCTG, which compared UFT/LV to UFT/PSK as adjuvant chemotherapy for stage IIB or III colorectal cancer in patients who had undergone Japanese D2/D3 lymph node dissection. METHODS: The primary endpoint was the 3-year disease-free survival (DFS)...
June 20, 2017: Surgery Today
https://www.readbyqxmd.com/read/28634727/safety-and-efficacy-of-chemosaturation-in-patients-with-primary-and-secondary-liver-tumors
#6
Martha M Kirstein, Steffen Marquardt, Nils Jedicke, Silke Marhenke, Wolfgang Koppert, Michael P Manns, Frank Wacker, Arndt Vogel
BACKGROUND: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; hepatic CHEMOSAT(®) delivery system; Delcath Systems Inc, USA) is a novel medical device, which delivers high doses of melphalan directly to the liver in patients with primary and secondary liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. The aim of this study was to analyze the safety and efficacy of the second-generation CS-PHP after 54 treatments at Hannover Medical School, Germany...
June 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28634627/influence-of-multiple-stapler-firings-used-for-rectal-division-on-colorectal-anastomotic-leak-rate
#7
Tamara Braunschmid, Nikolaus Hartig, Lukas Baumann, Bernhard Dauser, Friedrich Herbst
BACKGROUND: Anastomotic leakage following colorectal resection remains one of the most significant complications with relevant morbidity and mortality. There is evidence that a higher number of stapler firings for rectal division can affect the leak rate in double stapling anastomosis. However, there are no data concerning compression anastomosis. We present our institutional experience addressing this issue. DESIGN: This is a retrospective review of a prospective institutional database of patients undergoing colonic and rectal resection for benign and malignant indications between January 2008 and December 2014 at the surgical department of the St...
June 20, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28634498/evaluation-of-in-vitro-cytotoxicity-biocompatibility-and-changes-in-the-expression-of-apoptosis-regulatory-proteins-induced-by-cerium-oxide-nanocrystals
#8
Shahanavaj Khan, Anees A Ansari, Christian Rolfo, Andreia Coelho, Maha Abdulla, Khayal Al-Khayal, Rehan Ahmad
Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed...
2017: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/28633089/first-line-panitumumab-plus-folfox4-or-folfiri-in-colorectal-cancer-with-multiple-or-unresectable-liver-metastases-a-randomised-phase-ii-trial-planet-ttd
#9
Alfredo Carrato, Albert Abad, Bartomeu Massuti, Cristina Grávalos, Pilar Escudero, Federico Longo-Muñoz, José-Luis Manzano, Auxiliadora Gómez, María José Safont, Javier Gallego, Beatriz García-Paredes, Carles Pericay, Rosario Dueñas, Fernando Rivera, Ferrán Losa, Manuel Valladares-Ayerbes, Encarnación González, Enrique Aranda
BACKGROUND: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI...
June 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28632865/effect-of-first-line-chemotherapy-combined-with-cetuximab-or-bevacizumab-on-overall-survival-in-patients-with-kras-wild-type-advanced-or-metastatic-colorectal-cancer-a-randomized-clinical-trial
#10
Alan P Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Briant Fruth, Jeffrey A Meyerhardt, Deborah Schrag, Claire Greene, Bert H O'Neil, James Norman Atkins, Scott Berry, Blase N Polite, Eileen M O'Reilly, Richard M Goldberg, Howard S Hochster, Richard L Schilsky, Monica M Bertagnolli, Anthony B El-Khoueiry, Peter Watson, Al B Benson, Daniel L Mulkerin, Robert J Mayer, Charles Blanke
Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer...
June 20, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28632155/microbiota-inflammation-and-colorectal-cancer
#11
REVIEW
Cécily Lucas, Nicolas Barnich, Hang Thi Thu Nguyen
Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28631563/prognostic-significance-of-glutathione-peroxidase-2-in-gastric-carcinoma
#12
Dongzhe Liu, Liang Sun, Jinxue Tong, Xiuhui Chen, Hui Li, Qifan Zhang
Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631253/portal-branch-ligation-does-not-counteract-the-inhibiting-effect-of-temsirolimus-on-extrahepatic-colorectal-metastatic-growth
#13
Sebastian Senger, Jens Sperling, Barbara Oberkircher, Martin K Schilling, Otto Kollmar, Michael D Menger, Christian Ziemann
The mTor-inhibitor temsirolimus (TEM) has potent anti-tumor activities on extrahepatic colorectal metastases. Treatment of patients with advanced disease may require portal branch ligation (PBL). While PBL can induce intrahepatic tumor growth, the effect of PBL on extrahepatic metastases under TEM treatment is unknown. Therefore, we analyzed the effects of TEM treatment on extrahepatic metastases during PBL-associated liver regeneration. GFP-transfected CT26.WT colorectal cancer cells were implanted into the dorsal skinfold chamber of BALB/c-mice...
June 19, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28631086/nearly-a-third-of-high-grade-dysplasia-and-colorectal-cancer-is-undetected-in-patients-with-inflammatory-bowel-disease
#14
Swathi Eluri, Alyssa M Parian, Berkeley N Limketkai, Christina Y Ha, Steven R Brant, Sharon Dudley-Brown, Jonathan E Efron, Sandy G Fang, Susan L Gearhart, Michael R Marohn, Stephen J Meltzer, Safar Bashar, Brindusa Truta, Elizabeth A Montgomery, Mark G Lazarev
BACKGROUND: It is unclear whether intensive surveillance protocols have resulted in a decreased incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD). AIMS: To determine the prevalence and characteristics of IBD associated high-grade dysplasia (HGD) or CRC that was undetected on prior colonoscopy. METHODS: This is a single-center, retrospective study from 1994 to 2013. All participants had a confirmed IBD diagnosis and underwent a colectomy with either HGD or CRC found in the colectomy specimen...
June 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28629637/direct-medical-cost-associated-with-colorectal-cancer-in-north-of-jordan
#15
Qais Alefan, Rana Malhees, Nizar Mhaidat
Colorectal cancer (CRC) is mainly characterized as the malignant and impaired growth of rectal cells in the intestinal region. Direct medical cost is related to resources, which are directly used in treating the patient, that mainly includes the cost of drugs, diagnostic, treatment, follow-up, rehabilitation, and hospital admission. The objective of this study is to estimate and analyze direct medical costs attributable to CRC in Jordan. A retrospective analysis of a cohort patients treated for CRC data has been performed to determine direct medical costs attributable to CRC in Jordan...
May 15, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28628925/apoptosis-and-caspase-3-pathway-role-on-anti-proliferative-effects-of-scrophulariaoxy-sepala-methanolic-extract-on-caco-2-cells
#16
Ali Namvaran, Mehdi Fazeli, Safar Farajnia, Gholamreza Hamidian, Hassan Rezazadeh
Colorectal cancer is one the most important malignancies worldwide and finding new treatment option for this cancer is of high priority. Natural compounds are common source of drugs for treatment of various diseases including cancers. The aim of this study was to investigate the effects of Scrophularia oxysepala extract on Caco-2 cells and explore the possible role of caspase 3 pathway in inducing cell death in this cancer cells in compare with chemotherapy agents of cisplatin and capecitabine. The methanolic extract of Scrophularia oxysepala (SO) was prepared by drench method...
June 19, 2017: Drug Research
https://www.readbyqxmd.com/read/28628391/interest-and-attitudes-of-patients-with-advanced-cancer-with-regard-to-secondary-germline-findings-from-tumor-genomic-profiling
#17
Jada G Hamilton, Elyse Shuk, Margaux C Genoff, Vivian M Rodríguez, Jennifer L Hay, Kenneth Offit, Mark E Robson
PURPOSE: Tumor genomic profiling (TGP) can reveal secondary findings about inherited disease risks in a patient with cancer. Little is known about how patients with advanced cancer, currently the primary users of TGP, perceive the benefits and harms of secondary germline findings. METHODS: We conducted semistructured interviews with 40 patients with advanced breast, bladder, colorectal, or lung cancer who had TGP. Qualitative interview data were evaluated by using a thematic content analysis approach...
June 19, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#18
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627551/gold-loaded-nanoporous-iron-oxide-nanocubes-a-novel-dispersible-capture-agent-for-tumor-associated-autoantibody-analysis-in-serum
#19
Sharda Yadav, Mostafa Kamal Masud, Md Nazmul Islam, Vinod Gopalan, Alfred King-Yin Lam, Shunsuke Tanaka, Nam-Trung Nguyen, Md Shahriar Al Hossain, Cuiling Li, Md Yusuke Yamauchi, Muhammad J A Shiddiky
Autoantibodies are produced against tumor associated antigens (TAAs) long before the appearance of any symptoms and thus can serve as promising, non-invasive biomarkers for early diagnosis of cancer. Current conventional methods for autoantibody detection are highly invasive and mostly provide diagnosis in the later stages of cancer. Herein we report a new electrochemical method for early detection of p53 autoantibodies against colon cancer using a strategy that combines the strength of gold-loaded nanoporous iron oxide nanocube (Au@NPFe2O3NC)-based capture and purification while incorporating the inherent simplicity, inexpensive, and portable nature of the electrochemical and naked-eye colorimetric readouts...
June 19, 2017: Nanoscale
https://www.readbyqxmd.com/read/28626399/sigmoid-adenocarcinoma-with-regional-scrotal-metastasis
#20
Brenen P Swofford, Tomislav Dragovich
Colorectal cancer is a common disease, representing the third and second most common cause of cancer death in the United States in women and men, respectively. [Ahnen et al.: Mayo Clin Proc 2014;89: 216-224; Siegel et al.: CA Cancer J Clin 2016;66: 7]. It is estimated that 20% of patients have distant metastatic disease at time of diagnosis [Ahnen et al.: Mayo Clin Proc 2014;89: 216-224; Siegel et al.: CA Cancer J Clin 2016;66: 7]. The most common metastatic sites include regional lymph nodes, liver, lungs, and peritoneum via lymphatic/hematogenous dissemination as well as contiguous and transperitoneal routes [Ahnen et al...
May 2017: Case Reports in Oncology
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