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Michael L Schulte, Matthew R Hight, Gregory D Ayers, Qi Liu, Yu Shyr, M Kay Washington, H Charles Manning
PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF (V600E) , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
K Wolinski, A Stangierski, K Dyrda, K Nowicka, M Pelka, A Iqbal, A Car, M Lazizi, N Bednarek, A Czarnywojtek, E Gurgul, M Ruchala
PURPOSE: Acromegaly is a chronic disease resulting from pathological oversecretion of growth hormone and subsequently insulin growth factor-1. Several complications of the disease have been reported, including cardiovascular diseases, respiratory disorders but also increased risk of benign and malignant neoplasms. The aim of the study was to evaluate the risk of malignant neoplasms in the patients with acromegaly in comparison with the control group. PATIENTS AND METHODS: Medical documentation of acromegalic patients treated in one medical center between 2005 and 2016 has been analyzed...
October 21, 2016: Journal of Endocrinological Investigation
Paul H Sugarbaker
BACKGROUND: Mucinous appendiceal neoplasms (MAN) with peritoneal dissemination is treated as a standard of care using cytoreductive surgery and hyperthermic perioperative chemotherapy. The extent of the resection of peritoneal surfaces and visceral structures is generally well defined. Exception to this consensus regarding structures to be removed are the right colon and adjacent ileocolic lymph nodes. METHODS: From a prospectively maintained database, all patients with a histologic diagnosis of peritoneal mucinous carcinoma (PMCA) who underwent complete cytoreductive surgery were assessed for the presence versus absence of adenocarcinoma in lymph nodes within the appendiceal mesentery and/or in the lymph nodes of the ileocolic group...
October 21, 2016: Annals of Surgical Oncology
Jinke Xu, Mifong Tam, Sepideh Samadei, Sophie Lerouge, Jake Barralet, Mary M Stevenson, Marta Cerruti
Mucoadhesive drug delivery systems stick to mucosal tissues and prolong the local retention time of drugs. Since the colon is covered by a mucosal layer, mucoadhesive rectal formulations may improve treatment of such diseases as hypertension or colon cancer. Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the colonic mucosa. It is commonly treated with sulfasalazine (SSZ), which is metabolized by the intestinal flora into the therapeutic 5-aminosalicylic acid (5-ASA) and a toxic by-product sulfapyridine (SP)...
October 18, 2016: Acta Biomaterialia
Julia M Fraile, Diana Campos-Iglesias, Francisco Rodríguez, Yaiza Español, José M P Freije
Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis...
October 19, 2016: Oncotarget
Miao Liu, Ling Zhou, Baiyu Zhang, Minhong He, Xiaoying Dong, Xiaojun Lin, Chunhong Jia, Xiaochun Bai, Yifan Dai, Yongchun Su, Zhipeng Zou, Hang Zheng
Although epidemiological and preclinical studies have shown the preventative effect of n-3 polyunsaturated fatty acids (PUFAs) on colorectal cancer (CRC), the underlying molecular mechanisms are not clear. In this study, we revealed that elevation of n-3/n-6 PUFAs ratio suppress the mechanistic target of rapamycin complex 1 (mTORC1) and prevent colorectal tumorigenesis. The transgenic expression of fat-1, a desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3 PUFAs endogenously, repressed colorectal tumor cell growth and remarkably reduced tumor burden, and alleviated anemia as well as hyperlipidemia in APCMin/+ (adenomatous polyposis coli) mice, a classic CRC model that best simulates most clinical cases...
October 19, 2016: Oncotarget
Charles A Pickens, Mariana de Fátima Albuquerque Pereira, Jenifer I Fenton
Dietary lipid intake can be associated with an increased risk for colorectal cancer depending on its composition. Carcinogenesis alters lipid metabolism to facilitate cell growth and survival. For instance, metabolites of polyunsaturated fatty acids (PUFAs) are associated with increasing colon cell proliferation. Moreover, precancerous colon lesions (i.e. adenomas) increase the risk for colorectal cancer. In this study, we investigated associations between plasma PUFAs and the number of colon polyps and polyp type (i...
October 20, 2016: European Journal of Cancer Prevention
Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
Cuijuan Yu, Hai Wang, Aaron Muscarella, Amit Goldstein, Huan-Chang Zeng, Yangjin Bae, Brendan H I Lee, Xiang H-F Zhang
Intra-iliac artery (IIA) injection is an efficient approach to introduce metastatic lesions of various cancer cells in animals. Compared to the widely used intra-cardiac and intra-tibial injections, IIA injection brings several advantages. First, it can deliver a large quantity of cancer cells specifically to hind limb bones, thereby providing spatiotemporally synchronized early-stage colonization events and allowing robust quantification and swift detection of disseminated tumor cells. Second, it injects cancer cells into the circulation without damaging the local tissues, thereby avoiding inflammatory and wound-healing processes that confound the bone colonization process...
September 26, 2016: Journal of Visualized Experiments: JoVE
Fangyan Yu, Shruti Sharma, Agnieszka Skowronek, Kai Sven Erdmann
A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia...
October 21, 2016: Scientific Reports
Nitin R Gaikwad, Sudhir J Gupta, Amol R Samarth, Tushar H Sankalecha
Synchronous appearance of the primary gastrointestinal malignancies is rare. Coexistence of primary pancreatic and hepatocellular carcinoma as synchronous malignancy is even rarer. We report a case of such combination in a 50 year old female who presented with bleeding per rectum and while evaluating we found simultaneous appearance of primary malignancies of pancreas, liver and solitary colonic metastasis from the pancreas in the background of chronic calcific pancreatitis. To the best of our knowledge this combination of synchronous pancreatic and hepatocellular carcinoma and colonic metastasis from the pancreas is unique...
October 2016: Journal of the Association of Physicians of India
A Kautzky-Willer, S Thurner, P Klimek
AIM: There is firm evidence of a relation between type 2 diabetes (T2DM) and increased risks of cancer at various sites, but it is still unclear how different antihyperglycaemic therapies modify site-specific cancer risks. The aim of this study was to provide a complete characterization of all possible associations between individual T2DM therapies, statin use and site-specific cancers in the Austrian population. METHODS: Medical claims data of 1 847 051 patients with hospital stays during 2006-2007 were used to estimate age- and sex-dependent co-occurrences of site-specific cancer diagnoses and treatment with specific glucose-lowering drugs and statins...
October 21, 2016: Journal of Internal Medicine
Valentina Rosato, Alessandra Tavani, Esther Gracia-Lavedan, Elisabet Guinó, Gemma Castaño-Vinyals, Cristina M Villanueva, Manolis Kogevinas, Jerry Polesel, Diego Serraino, Federica E Pisa, Fabio Barbone, Victor Moreno, Carlo La Vecchia, Cristina Bosetti
BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of colorectal cancer, although the time-risk relationship is unclear, and there is limited information on the role of antidiabetic medications. AIM: We examined the association between type 2 diabetes, antidiabetic medications, and the risk of colorectal cancer, considering also duration of exposures. METHODS: We analyzed data derived from two companion case-control studies conducted in Italy and Spain between 2007 and 2013 on 1,147 histologically confirmed colorectal cancer cases and 1,594 corresponding controls...
2016: Frontiers in Oncology
Francesca Salamanna, Veronica Borsari, Silvia Brogini, Gianluca Giavaresi, Annapaola Parrilli, Simona Cepollaro, Matteo Cadossi, Lucia Martini, Antonio Mazzotti, Milena Fini
One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively...
October 19, 2016: Oncotarget
Hisato Kawakami, Shengbing Huang, Krishnendu Pal, Shamit K Dutta, Debabrata Mukhopadhyay, Frank A Sinicrope
Oncogenic BRAFV600E mutations activate MAP kinase signaling and are associated with treatment resistance and poor prognosis in patients with colorectal cancer (CRC). In BRAFV600E mutant CRCs, treatment failure may be related to BRAFV600E -mediated apoptosis resistance that occurs by an as yet undefined mechanism. We found that BRAFV600E can upregulate anti-apoptotic MCL-1 in a gene dose-dependent manner using CRC cell lines isogenic for BRAF. BRAFV600E -induced MCL-1 upregulation was confirmed by ectopic BRAFV600E expression that activated MEK/ERK signaling to phosphorylate (MCL-1Thr163) and stabilize MCL-1...
October 7, 2016: Molecular Cancer Therapeutics
Xiangyin Liu, Shengnan Liu, Xinyu Liu, Yunli Shi, Jinna Yang, Zhenhua Huang, Hongxia Zhao, Qingzhi Gao
Two novel fluorescent bioprobes, namely, 6N-Gly-Cy3 and 6N-Gly-Cy5, were designed and synthesized for real-time glucose transport imaging as well as potentially useful tracer for galactokinase metabolism. The structure of the bioprobes was fully characterized by (1)H NMR, (13)C NMR, IR, and HRMS. The fluorescence properties, glucose transporter (GLUT) specificity, and the quenching and safety profiles were studied. The cellular uptake of both bioprobes was competitively diminished by d-glucose, 2-deoxy-d-glucose and GLUT specific inhibitor in a dose-dependent manner in human colon cancer cells (HT29)...
October 17, 2016: Biochemical and Biophysical Research Communications
Prunella Blinman, Linda Mileshkin, Pearly Khaw, Geraldine Goss, Carol Johnson, Anne Capp, Susan Brooks, Gerard Wain, Ilka Kolodziej, Anne-Sophie Veillard, Rachel O'Connell, Carien L Creutzberg, Martin R Stockler
BACKGROUND: To determine the minimum survival benefits that patients, and their clinicians, judged sufficient to make adjuvant chemotherapy (ACT) worthwhile, in addition to pelvic radiotherapy, for women with high risk and advanced stage endometrial cancer. METHODS: Eighty-three participants in the PORTEC-3 trial completed a time trade-off questionnaire before and after adjuvant therapy; 44 of their clinicians completed it once only. The questionnaire used four hypothetical scenarios including baseline survival times without ACT of 5 and 8 years, and baseline survival rates at 5 years without ACT of 50 and 65%...
October 20, 2016: British Journal of Cancer
Yu-Chuan Huang, Chung-Ta Lee, Jenq-Chang Lee, Yao-Wen Liu, Ying-Jen Chen, Joseph T Tseng, Jui-Wen Kang, Bor-Shyang Sheu, Bo-Wen Lin, Liang-Yi Hung
MicorRNA-137 is silenced in human colorectal cancer tissues and colon polyps. Our study showed that the decreased expression of miR-137 is significantly different in various types of polyp which maintain different potentials to lead to CRC development. The expression of miR-137 gradually decreases during the process of colorectal carcinogenesis. Receiver operating characteristic curve (ROC) analysis indicates that the loss of miR-137 expression in colon polyps can serve as a biomarker to predict the predisposition of colorectal carcinogenesis...
October 18, 2016: Oncotarget
Urszula K Komarnicka, Radosław Starosta, Agnieszka Kyzioł, Michał Płotek, Małgorzata Puchalska, Małgorzata Jeżowska-Bojczuk
In this paper we present lomefloxacin's (HLm, 2nd generation fluoroquinolone antibiotic agent) organic and inorganic derivatives: aminomethyl(diphenyl)phosphine (PLm), its oxide as well as new copper(I) iodide or copper(I) thiocyanate complexes with PLm and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as the auxiliary ligands. The synthesized compounds were fully characterised by NMR, UV-Vis and luminescence spectroscopies. Selected structures were analysed by theoretical DFT (density functional theory) methods...
September 30, 2016: Journal of Inorganic Biochemistry
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