Looking for azaserine? Find out information about azaserine. C4H7O4N3 An antibiotic produced by a species of Streptomyces or by synthesis; used in treatment of acute leukemia Explanation of azaserine
Carboxymethylating agents are potential sources of endogenous DNA damage that have been proposed as possible contributors to gastrointestinal carcinogenesis. The cytotoxicity of the model DNA carboxymethylating agent azaserine was investigated in human cells. Expression of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) did not affect sensitivity to the drug in two related Raji Burkitts lymphoma cell lines. DNA mismatch repair-defective variants of Raji cells which display increased tolerance to DNA methylation damage were not selectively resistant to azaserine. Complementary results were obtained with a second carboxymethylating agent, potassium diazoacetate. In contrast, lymphoblastoid cell lines representative of each of the xeroderma pigmentosum complementation groups, including the variant, were all significantly more sensitive to azaserine than nucleotide excision repair-proficient cells. The hypersensitivity of XP cells was not due to systematic differences in the ...
Chemoprevention by retinoids of the progression of carcinomas induced in rats by azaserine was evaluated. Wistar/Lewis rats were given 15 weekly injections of azaserine, 10 mg/kg, while fed a chow diet; after the completion of carcinogen treatment, they were fed a chow diet supplemented with four different retinoids at the level of 0.5 to 2 mmol/kg diet for 1 year. The incidence of neoplasms was determined by autopsy and histological study. The incidence of pancreatic carcinoma among a male positive control group (azaserine treated, but not retinoid treated) was 42%. The incidence of pancreatic carcinoma among male rats treated with retinoids was: N-2-hydroxyethylretinamide, 6%; N-4-propionyloxyphenylretinamide, 17%; and retinylidene dimedone, 12%. The incidence in rats fed these three retinoids was significantly (p , 0.05) below the control group incidence. Thus, these three retinoids appeared to be effective in inhibiting the progression of pancreatic carcinomas in the azaserine-induced model. ...
The cardioprotective capacity and the influence on myocardial O-GlcNAc levels of plasma dialysate from eight healthy volunteers and eight type 2 diabetic patients drawn before and after subjection to an rIPC stimulus were tested on human isolated atrial trabeculae subjected to ischaemia/reperfusion injury. Dialysate from healthy volunteers exposed to rIPC improved post-ischaemic haemodynamic recovery (40 ± 6 vs. 16 ± 2%; P , 0.01) and increased myocardial O-GlcNAc levels. Similar observations were made with dialysate from diabetic patients before exposure to rIPC (43 ± 3 vs. 16 ± 2%; P , 0.001) but no additional cardioprotection or further increase in O-GlcNAc levels was achieved by perfusion with dialysate after exposure to rIPC (44 ± 4 and 42 ± 5 vs. 43 ± 3%; P = 0.7). The glutamine:fructose-6-phosphate amidotransferase (GFAT) inhibitor azaserine abolished the cardioprotective effects and the increment in myocardial O-GlcNAc levels afforded by plasma from diabetic patients and healthy ...
Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood. We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of
Researchers at the Johns Hopkins Kimmel Cancer Center have developed and tested a vaccine that triggered the growth of immune cell nodules within pancreatic tumors, essentially reprogramming these intractable cancers and potentially making them vulnerable to immune-based therapies.
So now there are 21 proteogenic amino acids…right?. Actually, there are 22 of them discovered till now. The last one is named Pyrrolysine, but it makes proteins only in prokaryotes (methanogenic archaea and bacteria).. So is there any other amino acids that are not "PROTEOGENIC"?. The proteogenic pool of amino acid is only a small part of the whole amino acid pool. There are many times more amino acids that dont produce proteins. Usually, the amino acids that dont have any associated genetic code wont produce proteins (they cant take part in translation), and so are non-proteogenic.. This is quite logical. Any organic molecule having at least one of each amine and carboxyl group can be called an amino acid and we have only limited number of genetic codes.. Examples of non-proteogenic amino acids are - ornithine, citrulline etc. in hepatic metabolism. The argininosuccinic acid in the urea cycle, S-adenosylmethionine, azaserine in streptomycin, synthetically produced (at least commercially) ...
TY - JOUR. T1 - Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis. T2 - Journal of Translational Medicine. AU - Grizzi, Fabio. AU - Fiorino, Sirio. AU - Qehajaj, Dorina. AU - Fornelli, Adele. AU - Russo, Carlo. AU - De Biase, Dario. AU - Masetti, Michele. AU - Mastrangelo, Laura. AU - Zanello, Matteo. AU - Lombardi, Raffaele. AU - Domanico, Andrea. AU - Accogli, Esterita. AU - Tura, Andrea. AU - Mirandola, Leonardo. AU - Chiriva-Internati, Maurizio. AU - Bresalier, Robert S.. AU - Jovine, Elio. AU - Leandri, Paolo. AU - Di Tommaso, Luca. N1 - Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.. PY - 2019/2/28. Y1 - 2019/2/28. N2 - Background: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a ...
Glutamine--fructose-6-phosphate transaminase 1 (GFAT1) catalyzes the formation of glucosamine 6-phosphate. It is the first and rate-limiting enzyme of the hexosamine pathway, in which fructose-6-phosphate is converted to N-acetylglucosamine-6-phosphate. The end-products of the hexosamine pathway are UDP-N-acetylglucosamine (UDP-GlcNAc) and other nucleotide hexosamines. Activation of the hexosamine pathway leads to insulin resistance, largely from deterioration of pancreatic beta-cell function through the induction of oxidative stress. GFAT1 is also known as glutamine:fructose 6 phosphate amidotransferase 1, hexosephosphate aminotransferase 1, D-fructose-6-phosphate amidotransferase 1, GFA, GFAT, GFPT, MSLG, CMSTA1, GFAT1m, and GFPT1L.. ...
Glutamine--fructose-6-phosphate transaminase 1 (GFAT1) catalyzes the formation of glucosamine 6-phosphate. It is the first and rate-limiting enzyme of the hexosamine pathway, in which fructose-6-phosphate is converted to N-acetylglucosamine-6-phosphate. The end-products of the hexosamine pathway are UDP-N-acetylglucosamine (UDP-GlcNAc) and other nucleotide hexosamines. Activation of the hexosamine pathway leads to insulin resistance, largely from deterioration of pancreatic beta-cell function through the induction of oxidative stress. GFAT1 is also known as glutamine:fructose 6 phosphate amidotransferase 1, hexosephosphate aminotransferase 1, D-fructose-6-phosphate amidotransferase 1, GFA, GFAT, GFPT, MSLG, CMSTA1, GFAT1m, and GFPT1L.. ...
Using immunohistochemistry, Northern blotting and a semi-quantitative PCR technique, epidermal growth factor (EGF), transforming growth factor-α (TGF-α) and epidermal growth factor receptor (EGFR) expression were studied in the pancreas of N-nitrosobis(2-oxopropyl)-amine (BOP)-treated hamsters. After initiation pancreatic carcinogenesis was modulated by a high fat diet or by injections with the cholecystokinin analogue caerulein. Autopsies were performed 6 and 12 months after the last injection with BOP. Immunohistochemistry revealed a weak expression of TGF-α innormal acinar cells and a stronger expression in ductular and centro-acinar cells. Over-expression of TGFα was observed in advanced putative preneoplastic lesions (classified as borderline lesions) and in ductular adenocarcinomas. EGFR immunoreactivity was present only in ductular adenocarcinomas. EGF peptide expression was observed both in acinar and ductular normal and tumorous cells and the level of expression did not change ...
From claims to limit its intake or cut it out altogether, its not uncommon for fat to be misrepresented. So when it comes to types whats the difference?
Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly immunosuppressive and heterogenous neoplasm. Despite improved knowledge regarding the genetic background of the tumor and better understanding of the tumor microenvironment, immune checkpoint inhibitor therapy (targeting CTLA4, PD1, PDL1) has not been very successful against PDAC. The robust desmoplastic stroma, along with an extensive extracellular matrix (ECM) that is rich in hyaluronan, plays an integral role in this immune evasion. Hexosamine biosynthesis pathway (HBP), a shunt pathway of glycolysis, is a metabolic node in cancer cells that can promote survival pathways on one hand and influence the hyaluronan synthesis in the ECM on the other. The rate-limiting enzyme of the pathway, glutamine-fructose amidotransferase (GFAT1), uses glutamine and fructose 6-phosphate to eventually synthesize UDP-GlcNAc. In the current manuscript, we targeted this glutamine-utilizing enzyme by a small molecule glutamine analog ...
Double bonds may be in either a cis or a trans isomer, depending on the geometry of the double bond. In the cis isomer, hydrogen atoms are on the same side of the double bond; whereas in the trans isomer, they are on opposite sides of the double bond (see trans fat). Saturated fats are useful in processed foods because saturated fats are less vulnerable to rancidity and usually more solid at room temperature than unsaturated fats. Unsaturated chains have a lower melting point, hence these molecules increase the fluidity of cell membranes. Although both monounsaturated and polyunsaturated fats can replace saturated fat in the diet, trans unsaturated fats should not. Replacing saturated fats with unsaturated fats helps lower levels of total cholesterol and LDL cholesterol in the blood.[1] Trans unsaturated fats are an exception because the double bond stereochemistry predisposes the carbon chains to assume a linear conformation, which conforms to rigid packing as in plaque formation. The geometry ...
Glukosamin pertama kali diidentifikasi oleh Dr. Georg Ledderhose pada tahun 1876, tetapi struktur stereokimia tidak sepenuhnya diketahui sampai ditemukan oleh Walter Haworth pada tahun 1939.[1] D-Glukosamin dibuat secara alami dalam bentuk glukosamin-6-fosfat, dan merupakan prekursor biokimia dari semua gula yang mengandung nitrogen.[2] Specifically, glucosamine-6-phosphate is synthesized from fructose-6-phosphate and glutamine[3] as the first step of the hexosamine biosynthesis pathway.[4] Produk akhir dari lintasan ini adalah UDP-N-asetilglukosamin (UDP-GlcNAc), yang kemudian digunakan untuk membentuk glikosaminoglikan, proteoglikan, dan glikolipid. Pembentukan glukosamin-6-fosfat merupakan tahap awal untuk menyintesis produk ini. Glukosamin merupakan komponen penting dalam meregulasi produksi senyawa tersebut. Walaupun demikian, bagaimana lintasan biosintesis heksoamin diregulasi dan bagaimana hal ini dapat berpengaruh terhadap penyakit manusia masih belum terlalu jelas [5] ...
Last time I wrote about saturated fat, typically considered a bad egg in the fats family. In that respect, unsaturated fat is treated as the golden child. The American Heart Association recommends getting most dietary fat from sources of unsaturated fats, rather than saturated or trans-fats. The Mayo Clinic more or less recommends the same. So,…
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We report that the relative β-cell volume in humans with both IFG and type 2 diabetes is decreased.. A limitation of the present studies is use of the relative β-cell volume as a surrogate of β-cell mass. This approach will be in error to the extent that there were differences in the overall mean pancreatic weight among groups. However, available data suggest that the pancreatic weight is similar (21,22) or decreased in patients with diabetes (9,27). If pancreatic weight is decreased in type 2 diabetes, then use of the insulin-positive area as a percentage of total exocrine area should introduce, if anything, a conservative error and underestimate any decrease in β-cell mass in type 2 diabetes. Earlier reports that the β-cell mass is decreased in type 2 diabetes may have included cases of type 1 diabetes (17,18). However, more recent reports in which clinical information was better characterized conclude that β-cell mass is decreased in type 2 diabetes (9,22,24), whereas others report no ...
Answers from doctors on biological compounds saturated vs unsaturated fats. First: Both these types of fat have been shown to reduce bad LDL cholesterol and increase good HDL cholesterol. Like any fat, they contain calories, so any extra fat should replace existing calories from saturated fat or carbohydrates.
Fats come in many forms and affect your health in different ways. Learn about fatty acids, saturated and unsaturated fats and the chemistry of fats.
The alteration of glucose metabolism, through increased uptake of glucose and glutamine addiction, is essential to cancer cell growth and invasion. Increased flux of glucose through the Hexosamine Biosynthetic Pathway (HBP) drives increased cellular O-GlcNAcylation (hyper-O-GlcNAcylation) and contributes to cancer progression by regulating key oncogenes. However, the association between hyper-O-GlcNAcylation and activation of these oncogenes remains poorly characterized. Here, we implement a qualitative modeling framework to analyze the role of the Biological Regulatory Network in HBP activation and its potential effects on key oncogenes. Experimental observations are encoded in a temporal language format and model checking is applied to infer the model parameters and qualitative model construction. Using this model, we discover step-wise genetic alterations that promote cancer development and invasion due to an increase in glycolytic flux, and reveal critical trajectories involved in cancer progression
The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have revealed that mutations in genes encoding different enzymes of the hexosamine biosynthetic pathway result in reduction of UDP-GlcNAc to different extents, with a consequent disruption of distinct glycosylation pathways and developmental processes. A maternal and zygotic loss-of-function screen has identified mutations in nesthocker (nst), which encodes an enzyme in the hexosamine biosynthetic pathway. Embryos lacking maternal and zygotic nst gene products show defective O-GlcNAcylation of a fibroblast growth factor receptor (FGFR)-specific adaptor protein, which impairs FGFR-dependent migration of mesodermal and tracheal cells.. ...
Unsaturated fats have been shown to improve health when used in place of other fats. There are two types of unsaturated fats, polyunsaturated and monounsaturated, both of which are liquid at room temperature. Two types of polyunsaturated fat, omega-3 and omega-6 fatty acids, cannot be produced by the human body, but play an essential role in brain development, skin and hair growth, bone health, maintaining a healthy reproductive system and even in regulating our metabolism. Plus, both types promote coronary health by lowering "bad" LDL cholesterol and raising "good" HDL cholesterol.. Dietary fats are an essential part of the human diet. Not only do they help us feel satisfied, they help the body use proteins and carbohydrates more efficiently. Fat also aids in the digestion of vitamins A, D, E and K. But as we know, not all fats are created equal. To increase your intake of unsaturated fats, try replacing other fatty foods with these 5 items:. 1. Olive Oil ...
Depending on the cellular context, transforming growth factor β (TGFβ) has been observed to exert protumorigenic functions, such as inducing an epithelial-mesenchymal transition (EMT), or inhibit tumorigenesis by activating apoptosis. The proapoptotic functions of TGFβ have been linked with the transcription factor SMAD4, which acts downstream of TGFβ and is frequently deleted in pancreatic ductal carcinoma (PDAC). To elucidate the mechanism by which TGFβ promotes apoptosis, David and colleagues used a Kras-mutant/Smad4-deleted PDAC murine model and found that reintroduction of SMAD4 sensitized cells to TGFβ treatment and promoted changes in cell morphology and loss of E-cadherin consistent with EMT. Moreover, SNAIL was shown to be upregulated following TGFβ treatment, and genetic depletion of SNAIL inhibited TGFβ-induced EMT, apoptosis, and accelerated pancreatic carcinogenesis in SMAD4-wild-type cells, raising the unexpected possibility that EMT precedes apoptosis and is required for ...
Proceddings of the Society of Experimental Biology and Medicine 1989 May;191(1):47-54 The effects of additional but nontoxic amounts of vitamin A on susceptibility to salmonella infection was studied by comparing rates of bacterial clearance and phagocytosis. Forty-eight male Lewis rats were divided into a treatment group receiving a total of 6000 units of vitamin A palmitate weekly for 5 weeks and a control group was given an equal volume of saline. After completion of the treatment regimen, one-half from each group were infected intraperitoneally with 10(5) Salmonella typhimurium; the other half received intraperitoneal injection of saline. At this time no differences in weight gain were noted and all animals were sacrificed within 2 weeks. At 72 hr after bacterial challenge, all saline-treated control animals displayed bacteremia. Cultures of liver and splenic homogenates were positive in 89 and 100% of infected control animals vs 0 and 44% for treated animals during the first week of ...
RESULTS: We defined three distinctive phases-termed inflammation, regeneration and refinement-following induction of moderate acute pancreatitis in wild-type mice. These corresponded to different waves of proliferation of mesenchymal, progenitor-like and acinar cells. Pancreas regeneration required a coordinated transition of proliferation between progenitor-like and acinar cells. In mice harbouring an oncogenic Kras mutation and challenged with pancreatitis, there was an extended inflammatory phase and a parallel, continuous proliferation of mesenchymal, progenitor-like and acinar cells. Analysis of high-resolution transcriptional data from wild-type animals revealed that organ regeneration relied on a complex interaction of a gene network that normally governs acinar cell homeostasis, exocrine specification and intercellular signalling. In mice with oncogenic Kras, a specific carcinogenic signature was found, which was preserved in full-blown mouse pancreas cancer ...
Molecular association of cancer cell metastasis with signaling pathways has been explicated so as to aid in the development of new prognostic models for better cancer therapies. However, those metastatic signaling pathways are barely explored to take account of the functions of enzymes involved in cellular metabolism. Particularly, the metabolic enzymes in de novo purine biosynthesis have been overlooked for their potential roles in cancer cell metastasis even though they have been successfully validated anti-cancer drug targets. Meanwhile, several lines of recent discoveries on de novo purine biosynthesis suggest that the spatiotemporal assembly of purine biosynthetic enzymes, the purinosome, is under controls of signaling pathways in cancer cells. The results of the inquiry reveal an unanticipated mechanism of action of 3-phosphoinositide-dependent protein kinase 1 (PDK1) signaling pathways in regulation of purine biosynthesis in an Akt-independent manner. Considering the biological action of ...
Fat" is a small world with a huge reputation. We are taught from a young age that fats are bad and we should stay away from them, but most people do not truly understand what a fat really is. Fat is the common name for the molecule triglyceride, which is an ester that comes from glycerol, a carbon chain with 3 hydroxyl substituents, and three fatty acids. The main two types of triglycerides are saturated and unsaturated fats, which differ in the bonding of the carbon chain in the molecule. The linear, saturated fats have all single carbon bonds and the maximum number of hydrogen bonds. This is unlike unsaturated fats, which have double bonds between some carbon atoms, creating a kink in the carbon chain. Although a double bond may not seem like a huge difference, on a molecular level it radically changes the properties of the molecule and the ways in which our bodies react to it. Within the realm of unsaturated fats, there are two geometric isomers that can exist. These are cis-fats and ...
Vitamin E Needs Increases with PUFA Consumption and Greater Unsaturation February 20, 2016 Posted in General.. Comments Off on Vitamin E Needs Increases with PUFA Consumption and Greater Unsaturation ...
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When is A Thyroid nodule with Hurthle cells not a neoplasm but part of a chronic thyroidits? Answer: When there are lymphocytes seen in the Hurthle cell nodule.. ...
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Pancreatic cancer is almost invariably associated with mutations in the KRAS gene, most commonly KRASG12D, that result in a dominant-active form of the KRAS GTPase. However, how KRAS mutations promote pancreatic carcinogenesis is not fully understood, and whether oncogenic KRAS is required for the maintenance of pancreatic cancer has not been established. To address these questions, we generated two mouse models of pancreatic tumorigenesis: mice transgenic for inducible KrasG12D, which allows for inducible, pancreas-specific, and reversible expression of the oncogenic KrasG12D, with or without inactivation of one allele of the tumor suppressor gene p53. Here, we report that, early in tumorigenesis, induction of oncogenic KrasG12D reversibly altered normal epithelial differentiation following tissue damage, leading to precancerous lesions. Inactivation of KrasG12D in established precursor lesions and during progression to cancer led to regression of the lesions, indicating that KrasG12D was ...
Majid Ali, M.D. OUTLINE I. Introduction II. Glycomics III. Complexities of Structure IV. Complexities of Function V. Cellular Glucose Oxidation VI. Carbohydrates and Generation of Reactive Oxygen Species VII. The Too-Much/Too-Little Sugar Dilemma VIII. Rapid Hyperglycemic-Hypoglycemic Shifts IX. Glucose Toxicity and Hexosamine Pathways X. Sugars and Prions XI. Sugars and the Inflammatory Response XII. Sugars,…
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Many plant foods are perfectly safe to eat raw, but soybeans arent among them. Some of the components found in raw soybeans can cause short term digestive problems, as well as possible long-term ...
Covering: up to the end of 2009 Detecting deficiency and excess of different metal ions is fundamental for every organism. Our understanding of how metals are detected by bacteria is exceptionally well advanced, and multiple families of cytoplasmic DNA-binding, metal-sensing transcriptional regul Metals in cells Focus on speakers from Biometals 2012
Doctors and nutritionists have long warned of the dangers of saturated and trans fats. But unsaturated fats are beneficial, particularly if eaten in place…