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https://www.readbyqxmd.com/read/28442505/overexpressed-fatty-acid-synthase-in-gastrointestinal-stromal-tumors-targeting-a-progression-associated-metabolic-driver-enhances-the-antitumor-effect-of-imatinib
#1
Chien-Feng Li, Fu-Min Fang, Yeng-Yang Chen, Ting-Ting Liu, Ti-Chun Chan, Shih-Chen Yu, Li-Tzong Chen, Hsuan-Ying Huang
Purpose: In gastrointestinal stromal tumors (GISTs), lipid-metabolizing enzymes remain underexplored, including fatty acid synthase (FASN). <p>Experimental Design: Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by RNA interference or myristoylated-AKT transfection...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28429738/fatty-acid-synthase-cooperates-with-protrudin-to-facilitate-membrane-outgrowth-of-cellular-protrusions
#2
Chuanling Zhang, Jiaqi Lu, Huizhong Su, Jing Yang, Demin Zhou
Cellular protrusion formation capacity is a key feature of developing neurons and many eukaryotic cells. However, the mechanisms underlying membrane growth in protrusion formation are largely unclear. In this study, photo-reactive unnatural amino acid 3-(3-methyl-3H-diazirin-3-yl)-propamino-carbonyl-Nε-l-lysine was incorporated by a genetic code expansion strategy into protrudin, a protein localized in acidic endosomes and in the endoplasmic reticulum, that induces cellular protrusion and neurite formation...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28418352/-fatty-acid-synthase-in-the-diagnosis-of-prostate-neoplasms
#3
D O Allina, Yu Yu Andreeva, L E Zavalishina, L V Moskvina, G A Frank
The differential diagnosis of benign and malignant changes in the prostate presents still definite difficulties; the antibody panel existing for these purposes is imperfect. Fatty acid synthase (FASN) is an androgen-regulated enzyme required for de novo lipogenesis. A number of studies have noted increased expression of the gene encoding this protein in tumors and precancerous lesions of different locations. AIM: Тo estimate the diagnostic value of analyzing the expression of FASN in prostate neoplasias...
2017: Arkhiv Patologii
https://www.readbyqxmd.com/read/28407230/acyl-coa-synthetase-short-chain-family-member-2-acss2-is-regulated-by-srebp-1-and-plays-a-role-in-fatty-acid-synthesis-in-caprine-mammary-epithelial-cells
#4
Huifen Xu, Jun Luo, Gongzhen Ma, Xueying Zhang, Dawei Yao, Ming Li, Juan J Loor
Sterol regulatory element binding protein 1 (SREBP-1) is well-known as the master regulator of lipogenesis in rodents. Acyl-CoA synthetase short-chain family member 2 (ACSS2) plays a key role in lipogenesis by synthesizing acetyl-CoA from acetate for lipogenesis. ATP citrate lyase (ACLY) catalyzes the conversion of citrate and coenzyme A to acetyl-CoA, hence, it is also important for lipogenesis. Although ACSS2 function in cancer cells has been elucidated, its essentiality in ruminant mammary lipogenesis is unknown...
April 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28400509/oncogene-kras-activates-fatty-acid-synthase-resulting-in-specific-erk-and-lipid-signatures-associated-with-lung-adenocarcinoma
#5
Arvin M Gouw, Livia S Eberlin, Katherine Margulis, Delaney K Sullivan, Georgia G Toal, Ling Tong, Richard N Zare, Dean W Felsher
KRAS gene mutation causes lung adenocarcinoma. KRAS activation has been associated with altered glucose and glutamine metabolism. Here, we show that KRAS activates lipogenesis, and this activation results in distinct proteomic and lipid signatures. By gene expression analysis, KRAS is shown to be associated with a lipogenesis gene signature and specific induction of fatty acid synthase (FASN). Through desorption electrospray ionization MS imaging (DESI-MSI), specific changes in lipogenesis and specific lipids are identified...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28387458/anti-tumorigenic-potential-of-a-novel-orlistat-aicar-combination-in-prostate-cancer-cells
#6
Clayton Wright, Anand Krishnan V Iyer, Vivek Kaushik, Neelam Azad
Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men worldwide. Fatty acid synthase (FASN) is reported to be overexpressed in several cancers including PCa, and this has led to clinical cancer treatments that utilize various FASN inhibitors such as the anti-obesity drug, Orlistat. However, pharmacological limitations have impeded the progress in cancer treatments expected thus far with FASN inhibition. In this study, we investigated a novel therapeutic combination to enhance the toxic potential of Orlistat in three different PCa cell-lines (DU145, PC3, and LNCaP)...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28386750/fatty-acid-synthase-regulates-the-chemosensitivity-of-breast-cancer-cells-to-cisplatin-induced-apoptosis
#7
Shadia Al-Bahlani, Hanaa Al-Lawati, Moza Al-Adawi, Nadia Al-Abri, Buthaina Al-Dhahli, Kawther Al-Adawi
Fatty acid synthase (FASN) is a key enzyme in fat biosynthesis that is over-expressed in advanced breast cancer stages. Cisplatin (CDDP) is a platinum-based drug used in the treatment of certain types of this disease. Although it was shown that FASN inhibition induced apoptosis by enhancing the cytotoxicity of certain drugs in breast cancer, its role in regulating the chemosensitivity of different types of breast cancer cells to CDDP-induced apoptosis is not established yet. Therefore, two different breast cancer cell lines; triple negative breast cancer (TNBC; MDA-MB-231) and triple positive breast cancer (TPBC; BT-474) cells were used to examine such role...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28386316/energy-intake-correlates-with-the-levels-of-fatty-acid-synthase-and-insulin-like-growth-factor-1-in-male-and-female-c57bl-6-mice
#8
Anup S Ramdhave, Shreesh Ojha, Mukesh Nandave
Emerging evidence suggests that, dysregulation of fatty acid synthase (FASN) and insulin-like growth factor-1 (IGF-1) could play a vital role in pathology of various diseases. Our aim was to determine the changes in FASN and IGF-1 levels concomitant to long term feeding of HFD in either sex. Male and female mice were fed either HFD or LFD for a period of 16 weeks. During this period, physiological, biochemical, and histological parameters were evaluated. Mice fed with HFD showed a significant gain in body weight, body mass index, energy intake, and abdominal circumference...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385599/intramyocellular-lipid-content-and-lipogenic-gene-expression-responses-following-a-single-bout-of-resistance-type-exercise-differ-between-young-and-older-men
#9
Kostas Tsintzas, Francis B Stephens, Tim Snijders, Benjamin T Wall, Scott Cooper, Joanne Mallinson, Lex B Verdijk, Luc J C van Loon
The aim of this study was to examine the temporal relationship between intramyocellular lipid (IMCL) content and the expression of genes associated with IMCL turnover, fat metabolism, and inflammation during recovery from an acute bout of resistance type exercise in old versus young men. Seven healthy young (23±2years, 77.2±2.9kg) and seven healthy older (72±1years, 79.3±4.9kg) males performed a single bout of resistance exercise involving 6 sets of 10 repetitions of leg press and 6 sets of 10 repetitions of leg extension at 75% one-repetition maximum (1-RM)...
April 3, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28380195/duodenal-jejunal-bypass-normalizes-pancreatic-islet-proliferation-rate-and-function-but-not-hepatic-steatosis-in-hypothalamic-obese-rats
#10
K R Cantelli, G M Soares, R A Ribeiro, S L Balbo, C Lubaczeuski, A C Boschero, A C F Araújo, M L Bonfleur
Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL)...
March 30, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28375178/are-mirna-103-mirna-107-and-mirna-122-involved-in-the-prevention-of-liver-steatosis-induced-by-resveratrol
#11
Ana Gracia, Alfredo Fernández-Quintela, Jonatan Miranda, Itziar Eseberri, Marcela González, María P Portillo
The aim of the present study was to determine whether the reduction in liver fat previously observed in our laboratory in a cohort of rats which had been fed an obesogenic diet was mediated by changes in the expression of microRNA (miRNA)-103-3p, miRNA-107-3p and miRNA-122-5p, which represent 70% of total miRNAs in the liver, as well as in their target genes. The expression of the three analysed miRNAs was reduced in rats treated with resveratrol. A reduction in sterol-regulatory element binding protein 1 (SREBP1) and an increase in carnitine palmitoyltransferase 1a (CPT1a) were observed in resveratrol-treated rats...
April 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28342983/lipid-quantification-by-raman-microspectroscopy-as-a-potential-biomarker-in-prostate-cancer
#12
Jordan O'Malley, Rahul Kumar, Andrey N Kuzmin, Artem Pliss, Neelu Yadav, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Paras N Prasad, Dhyan Chandra
Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort...
March 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28339092/macc1-decreases-the-chemosensitivity-of-gastric-cancer-cells-to-oxaliplatin-by-regulating-fasn-expression
#13
Jiangman Duan, Lishan Chen, Minyu Zhou, Jingwen Zhang, Li Sun, Na Huang, Jianping Bin, Yulin Liao, Wangjun Liao
The effect of chemotherapeutic agents is limited as a result of drug resistance, which demands prompt solutions provided by clinical studies. To date, the underlying mechanisms of chemotherapy resistance are relatively unknown. Metastasis-associated in colon cancer 1 (MACC1) is an oncogene associated with the progression and prognosis of gastric cancer (GC). Bioinformatic analysis revealed that MACC1 is positively associated with fatty acid synthase (FASN), a major enzyme of lipogenesis, and drives chemoresistance to oxaliplatin in GC...
March 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28298542/lipid-emulsion-added-to-a-liquid-high-carbohydrate-diet-and-voluntary-running-exercise-reduce-lipogenesis-and-ameliorate-early-stage-hepatic-steatosis-in-mice
#14
Kuan-Hsun Huang, Lei Hao, Philip B Smith, Connie J Rogers, Andrew D Patterson, A Catharine Ross
Background: The use of parenteral nutrition formulas is often associated with the development of hepatic steatosis. We have shown previously that the addition of a lipid emulsion (LE) rich in n-6 (ω-6) fatty acids (FAs) ameliorated triglyceride (TG) accumulation in the livers of nonobese mice fed a high-carbohydrate diet (HCD) for 5 wk. However, it remains unclear how rapidly this condition develops and whether it can be prevented by LE with or without a running wheel for voluntary exercise (Exe).Objective: We investigated in an 8-d study whether mice develop steatosis and whether the administration of LE with or without Exe reduces the concentration of total FAs and prevents an increase in the expression of genes in the liver associated with lipogenesis...
March 15, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28292742/fatty-acid-synthesis-intermediates-represent-novel-noninvasive-biomarkers-of-prostate-cancer-chemoprevention-by-phenethyl-isothiocyanate
#15
Krishna B Singh, Shivendra V Singh
Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model...
March 14, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28284693/the-effects-of-cell-death-inducing-dna-fragmentation-factor-%C3%AE-like-effector-c-cidec-on-milk-lipid-synthesis-in-mammary-glands-of-dairy-cows
#16
Yang Yang, Ye Lin, Xiaoyu Duan, He Lv, Weinan Xing, Qingzhang Li, Xuejun Gao, Xiaoming Hou
Adequate lipid synthesis by the mammary gland during lactation is essential for the survival of mammalian offspring. Cell death-inducing DNA fragmentation factor-α-like effector C (CIDEC) is a lipid droplet-associated protein and functions to promote lipid accumulation and inhibit lipolysis in mice and human adipocytes. However, the function of CIDEC in regulation of milk lipid synthesis in dairy cow mammary gland remains largely unknown. In this study, 6 multiparous Holstein cows (parity = 3) in early lactation were allocated to high-fat milk (milk yield 33...
May 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28268248/dietary-glycemic-and-insulin-scores-and-colorectal-cancer-survival-by-tumor-molecular-biomarkers
#17
NaNa Keum, Chen Yuan, Reiko Nishihara, Emilie Zoltick, Tsuyoshi Hamada, Alejandro Martinez Fernandez, Xuehong Zhang, Akiko Hanyuda, Li Liu, Keisuke Kosumi, Jonathan A Nowak, Iny Jhun, T Rinda Soong, Teppei Morikawa, Fred K Tabung, Zhi Rong Qian, Charles S Fuchs, Jeffrey A Meyerhardt, Andrew T Chan, Kimmie Ng, Shuji Ogino, Edward L Giovannucci, Kana Wu
Accumulating evidence suggests that post-diagnostic insulin levels may influence colorectal cancer (CRC) survival. Yet, no previous study has examined CRC survival in relation to a post-diagnostic diet rich in foods that increase post-prandial insulin levels. We hypothesized that glycemic and insulin scores (index or load; derived from food frequency questionnaire data) may be associated with survival from specific CRC subtypes sensitive to the insulin signaling pathway. We prospectively followed 1,160 CRC patients from the Nurses' Health Study (1980-2012) and Health Professionals Follow-Up Study (1986-2012), resulting in 266 CRC deaths in 10,235 person-years...
March 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28260110/inhibitory-effect-of-emodin-on-fatty-acid-synthase-colon-cancer-proliferation-and-apoptosis
#18
Kyung Ha Lee, Myung Sun Lee, Eun Young Cha, Ji Young Sul, Jin Sun Lee, Jin Su Kim, Jun Beom Park, Ji Yeon Kim
Fatty acid synthase (FASN) is a key anabolic enzyme for de novo fatty acid synthesis, which is important in the development of colon carcinoma. The high expression of FASN is considered a promising molecular target for colon cancer therapy. Emodin, a naturally occurring anthraquinone, exhibits an anticancer effect in various types of human cancer, including colon cancer; however, the molecular mechanisms remain to be fully elucidated. Cell viability was evaluated using a Cell Counting Kit‑8 assay. The apoptosis rate of cells was quantified via flow cytometry following Annexin V/propidium iodide staining...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28240737/fatty-acid-synthase-regulates-estrogen-receptor-%C3%AE-signaling-in-breast-cancer-cells
#19
J A Menendez, R Lupu
Fatty acid synthase (FASN), the key enzyme for endogenous synthesis of fatty acids, is overexpressed and hyperactivated in a biologically aggressive subset of sex steroid-related tumors, including breast carcinomas. Using pharmacological and genetic approaches, we assessed the molecular relationship between FASN signaling and estrogen receptor alpha (ERα) signaling in breast cancer. The small compound C75, a synthetic slow-binding inhibitor of FASN activity, induced a dramatic augmentation of estradiol (E2)-stimulated, ERα-driven transcription...
February 27, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28237595/effect-of-short-term-feed-restriction-on-temporal-changes-in-milk-components-and-mammary-lipogenic-gene-expression-in-mid-lactation-holstein-dairy-cows
#20
A M Abdelatty, M E Iwaniuk, M Garcia, K M Moyes, B B Teter, P Delmonte, A K G Kadegowda, M A Tony, F F Mohamad, R A Erdman
Investigations of the temporal changes in mammary gene expression that occur during sudden diet change have been limited by the use of mammary tissue as the source of RNA because of the invasive nature of mammary biopsy procedures. However, the cytosolic crescent, present in 1% of the largest milk fat globules, contains mammary epithelial cell RNA that has become trapped between the inner and outer milk fat globule membranes during final formation and secretion of milk fat into the lumen of the mammary alveoli...
May 2017: Journal of Dairy Science
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