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Amino Acid And Cancer Cells

Yanyan Xia, Yuanying Zhang, Mengjiao Shen, Hongpan Xu, Zhiyang Li, Nongyue He
Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis-Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non-viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings...
October 19, 2018: Cell Proliferation
Rituraj Pal, Michela Palmieri, Arindam Chaudhury, Tiemo Jürgen Klisch, Alberto di Ronza, Joel R Neilson, George G Rodney, Marco Sardiello
The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell survival and autophagy, and its activity is regulated by amino acid availability. Rag GTPase-GATOR1 interactions inhibit mTORC1 in the absence of amino acids, and GATOR1 release and activation of RagA/B promotes mTORC1 activity in the presence of amino acids. However, the factors that play a role in Rag-GATOR1 interaction are still poorly characterized. Here, we show that the tyrosine kinase Src is crucial for amino acid-mediated activation of mTORC1...
October 19, 2018: Nature Communications
Kensuke Yotsumoto, Kenta Ishii, Miho Kokubo, Sakiko Yasuoka
Polymeric micelles, which form through the self-assembly of poly(ethylene glycol)-poly(amino acid) block copolymers, are systemic nanocarriers in targeted cancer therapy. These micelles can encapsulate therapeutic compounds, such as lipophilic substances, charged compounds, and metal complexes, that have characteristics of increased solubility, sustained release, and improved tissue distribution. However, few studies have been conducted on the local distribution of polymeric micelles. Thus, we evaluated the skin penetration pattern of hydrophobic drugs in polymeric micelles...
October 16, 2018: International Journal of Pharmaceutics
Rodolfo Servín-Blanco, Rosa Mariana Chávaro-Ortiz, Rubén Zamora-Alvarado, Fernando Martínez-Cortes, Goar Gevorkian, Karen Manoutcharian
Although various immune checkpoint inhibitors (ICIs), used for the treatment of advanced cancer, showed remarkably durable tumor regression in a subset of patients, there are important limitations in a large group of non-responders, and the generation of novel immunogens capable of inducing protective cellular immune responses is a priority in cancer immunotherapy field. During the last decades, several types of vaccine immunogens have been used in numerous preclinical studies and clinical trials. However, although immunity to tumor Ags can be elicited by most vaccines tested, their clinical efficacy remains modest...
October 16, 2018: Immunology Letters
Takefumi Komiya, Chao H Huang
Recent application of immunotherapy in clinical oncology revolutionized our management of advanced human cancers. Check point inhibitors targeting CTLA4 and PD-1/PD-L1 axis are immunotherapeutic agents currently available to treat a variety of cancers. However, a novel therapeutic approach is needed to further improve patient outcome with these agents. Indoleamine 2,3-dioxygenase 1 (IDO1) is a rate-limiting enzyme in the metabolism of essential amino acid tryptophan in the peripheral tissue. IDO1 is overexpressed in human cancer cells and suppresses effector T cell function and promotes regulatory T cells (Tregs)...
2018: Frontiers in Oncology
Elke M Muntjewerff, Gina Dunkel, Mara J T Nicolasen, Sushil K Mahata, Geert van den Bogaart
It is increasingly clear that inflammatory diseases and cancers are influenced by cleavage products of the pro-hormone chromogranin A (CgA), such as the 21-amino acids long catestatin (CST). The goal of this review is to provide an overview of the anti-inflammatory effects of CST and its mechanism of action. We discuss evidence proving that CST and its precursor CgA are crucial for maintaining metabolic and immune homeostasis. CST could reduce inflammation in various mouse models for diabetes, colitis and atherosclerosis...
2018: Frontiers in Immunology
Madhusmita Rout, Sajitha Lulu S
Discerning the relationship between molecules involved in diseases based on their underlying biological mechanisms is one of the greatest challenges in therapeutic development today. Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, which adversely affects both mothers and offspring during and after pregnancy. We have constructed two datasets of (GDM associated genes from affected mother and placenta to systematically analyze and evaluate their interactions like gene-gene, gene-protein, gene-microRNA (miRNA), gene-transcription factors, and gene-associated diseases to enhance our current knowledge, which may lead to further advancements in disease diagnosis, prognosis, and treatment...
October 18, 2018: Journal of Cellular Biochemistry
Tateaki Naito, Shuichi Mitsunaga, Satoru Miura, Noriatsu Tatematsu, Toshimi Inano, Takako Mouri, Tetsuya Tsuji, Takashi Higashiguchi, Akio Inui, Taro Okayama, Teiko Yamaguchi, Ayumu Morikawa, Naoharu Mori, Toshiaki Takahashi, Florian Strasser, Katsuhiro Omae, Keita Mori, Koichi Takayama
BACKGROUND: Combinations of exercise and nutritional interventions might improve the functional prognosis for cachectic cancer patients. However, high attrition and poor compliance with interventions limit their efficacy. We aimed to test the feasibility of the early induction of new multimodal interventions specific for elderly patients with advanced cancer Nutrition and Exercise Treatment for Advanced Cancer (NEXTAC) programme. METHODS: This was a multicentre prospective single-arm study...
October 18, 2018: Journal of Cachexia, Sarcopenia and Muscle
Hitomi Sudo, Atsushi B Tsuji, Aya Sugyo, Maki Okada, Koichi Kato, Ming-Rong Zhang, Tsuneo Saga, Tatsuya Higashi
The non‑natural amino acid positron emission tomography tracers, 2‑amino[3‑11C]isobutyric acid ([3‑11C]AIB) and 2‑amino[11C]methyl‑isobutyric acid ([11C]MeAIB), are metabolically stable in vivo and accumulate in tumors. [3‑11C]AIB is transported into cells mainly via the amino acid transport system A and partially via systems L and ASC, whereas [11C]MeAIB is transported into cells specifically via system A. How transport via the different systems affects the tumor uptake of these tracers, however, is unclear...
October 16, 2018: International Journal of Oncology
Sushil K Kashaw, Shivangi Agarwal, Mitali Mishra, Samaresh Sau, Arun Iyer
INTRODUCTION: Caspase-3 plays a leading role in apoptosis and on activation, it cleaves many protein substrates in cells and causes cell death. Since many chemotherapeutics are known to induce apoptosis in cancer cells, promotion or activation of apoptosis via targeting apoptosis regulators has been suggested as a promising strategy for anticancer drug discovery. In this paper, we studied the interaction of 1,2,4-Oxadiazoles derivatives with anticancer drug target enzymes (PDB ID 3SRC)...
October 15, 2018: Current Computer-aided Drug Design
Phongphat Obounchoey, Lueacha Tabtimmai, Praphasri Suphakun, Kannika Thongkhao, Chatchakorn Eurtivong, Matthew Paul Gleeson, Kiattawee Choowongkomon
The epidermal growth factor receptor (EGFR) was found to be overexpressed in several cancers, especially in lung cancers. Finding new effective drug against EGFR is the key to cancer treatment. In this study, the GOLD docking algorithm was used to virtually screen for novel human EGFR inhibitors from the NCI database. Thirty-four hit compounds were tested for EGFR-tyrosine kinase (TK) inhibition. Two potent compounds, 1-amino-4-(4-[4-amino-2-sulfophenyl]anilino)-9,10-dioxoanthracene-2-sulfonic acid (NSC125910), and nogalamycin N-oxide (NSC116555) were identified with IC50 values against EGFR-TK comparable to gefitinib; 16...
October 15, 2018: Journal of Cellular Biochemistry
Shan Jiang, Ting Lin, Qingji Xie, Lijing Wang
The RAD51 (DNA repair protein RAD51) recombinases are essential for homologous recombination, DNA repair, and genome stability. Overexpression of RAD51 proteins has been observed in many cancer cells, such as thyroid carcinoma, breast cancer, pancreatic cancer, and others. In Metazoa, there are multiple members of RAD51 (RAD51, RAD51B, RAD51C, RAD51D, DMC1) (DNA meiotic recombinase 1), XRCC2 (X-ray repair cross-complementing 2), and XRCC3. In this study, we used a protein sequence similarity network (SSN) to analyze the evolutionary relationship within this protein family...
2018: Frontiers in Genetics
Elitsa A Ananieva, Joshua N Bostic, Ashley A Torres, Hannah R Glanz, Sean M McNitt, Michelle K Brenner, Michael P Boyer, Adele K Addington, Susan M Hutson
BACKGROUND: The mitochondrial branched-chain aminotransferase (BCATm) is a recently discovered cancer marker with a poorly defined role in tumour progression. METHODS: To understand how a loss of function of BCATm affects cancer, the global knockout mouse BCATmKO was challenged with EL-4 lymphoma under different diet compositions with varying amounts of branched-chain amino acids (BCAAs). Next, the growth and metabolism of EL-4 cells were studied in the presence of different leucine concentrations in the growth medium...
October 15, 2018: British Journal of Cancer
Milena Čolović, Etienne Rousseau, Zhengxing Zhang, Joseph Lau, Chengcheng Zhang, Hsiou-Ting Kuo, Hua Yang, Paul Schaffer, François Bénard, Kuo-Shyan Lin
In this study, we synthesized 18 F-ASu-BF3 , a close boramino acid analog of 5-[18 F]fluoro-aminosuberic acid (18 F-ASu), via 18 F-19 F isotope exchange reaction and evaluated its potential for imaging with positron emission tomography (PET). 18 F-ASu-BF3 was stable in mouse plasma and taken up into PC3 prostate cancer cells via the system xC - amino acid transporter. The continuous use of isoflurane for anesthesia during dynamic imaging acquisition slowed down the excretion of 18 F-ASu-BF3 and enabled visualization of PC3 tumor xenografts in mice...
June 8, 2018: Bioorganic & Medicinal Chemistry Letters
Sungwoo Hong, Zhenghuan Fang, Hoi-Yun Jung, Jin-Ha Yoon, Soon-Sun Hong, Han-Joo Maeng
To investigate the amino acid transporter-based prodrug anticancer strategy further, several amino acid-conjugated amide gemcitabine prodrugs were synthesized to target amino acid transporters in pancreatic cancer cells. The structures of the synthesized amino acid-conjugated prodrugs were confirmed by ¹H-NMR and LC-MS. The pancreatic cancer cells, AsPC1, BxPC-3, PANC-1 and MIAPaCa-2, appeared to overexpress the amino acid transporter LAT-1 by conventional RT-PCR. Among the six amino acid derivatives of gemcitabine, threonine derivative of gemcitabine (Gem-Thr) was more effective than free gemcitabine in the pancreatic cancer cells, BxPC-3 and MIAPaCa-2, respectively, in terms of anti-cancer effects...
October 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Tiina Rasila, Olga Saavalainen, Hesham Attalla, Petri Lankila, Caj Haglund, Erkki Hölttä, Leif C Andersson
Our group originally found and cloned cDNA for a 98 kDa type 1 transmembrane glycoprotein of unknown function. Due to its abundant expression in astrocytes it was called the protein astroprincin (APCN). Two thirds of the evolutionarily conserved protein is intracytoplasmic whereas the extracellular domain carries two N-glycosidic side chains. APCN is physiologically expressed in placental trophoblasts, skeletal and hearth muscle, and kidney and pancreas. Overexpression of APCN (cDNA) in various cell lines induced sprouting of slender projections whereas knockdown of APCN expression by siRNA caused disappearance of actin stress fibres...
October 9, 2018: American Journal of Pathology
Zbigniew J Grzywna, Przemyslaw Borys
Using the results from previous modeling of the ball and chain inactivation of the potassium channels we try to model the inactivation of the NaV 1.5 sodium channels in adult and neonatal form. The (fast) inactivation of sodium channels differs from the inactivation of the potassium channels by the use of a inactivating hinge rather than a ball on a chain. The adult and neonatal variants of the channel differ mostly in a charged amino acid residue located on the extracellular side. We show that a drift caused by this residue is sufficient to describe the differences in inactivation between the two forms of the NaV 1...
October 8, 2018: Bio Systems
Huimei Zheng, Yafei Zhang, Yuchen Chen, Pengfei Guo, Xuexiang Wang, Xin Yuan, Wanzhong Ge, Ru Yang, Qingfeng Yan, Xiaohang Yang, Yongmei Xi
CD133 (AC133/prominin-1) has been identified as a stem cell marker and a putative cancer stem cell marker in many solid tumors. Its biologic function and molecular mechanisms remain largely elusive. Here, we show that a fly mutant for prominin-like, a homolog of mammalian CD133, shows a larger body size and excess weight accompanied with higher fat deposits as compared with the wild type. The expression levels of prominin-like are mediated by ecdysone signaling where its protein levels increase dramatically in the fat body during metamorphosis...
October 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Shan Tang, Na Zhang, Yue Zhou, Wilian A Cortopassi, Matthew P Jacobson, Li-Jiao Zhao, Ru-Gang Zhong
Protein kinase CK2 is considered as an emerging target in cancer therapy, and recent efforts have been made to develop its ATP-competitive inhibitors, but achieving selectivity with respect to related kinases remains challenging because of the highly conserved ATP-binding pocket of kinases. Non-ATP competitive inhibitors might solve this challenge; one such strategy is to identify compounds that target the CK2α/CK2β interface as CK2 holoenzyme antagonists. Here we improved the binding affinity to CK2α and cell-based anti-cancer activity of a CK2β-derived cyclic peptide (Pc) by combining structure-based computational design with experimental evaluation...
October 11, 2018: Molecular Informatics
Rudrax N S Priolkar, Sunil Shingade, Mahesh Palkar, Shivalingrao Mamle Desai
BACKGROUND: According to WHO, in 2017, about 90.5 million of people suffer from cancer and about 8.8 million deaths occurred due to disease. Although the chemotherapeutic agents have decreased the mortality among the cancer patients but high toxicity and non-specific targets are still major drawbacks. Many researchers have identified linomide, a 4-hydroxy-2-quinolone derivative, as a lead molecule for the development of anticancer agents. With this background we thought of the following objective...
October 8, 2018: Current Drug Discovery Technologies
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