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Amino Acid And Cancer Cells

Michihiko Aoyama, Minoru Tada, Ken-Ichiro Tatematsu, Noritaka Hashii, Hideki Sezutsu, Akiko Ishii-Watabe
Recombinant monoclonal antibodies (mAbs) have been used in various therapeutic applications including cancer therapy. Fc-mediated effector functions play a pivotal role in the tumor-killing activities of some tumor-targeting mAbs, and Fc-engineering technologies with glyco-engineering or amino acid substitutions at the antibody Fc region have been used to enhance cytotoxic activities including antibody-dependent cellular cytotoxicity (ADCC). We previously reported that the mAbs produced using transgenic silkworms showed stronger ADCC activity and lower complement-dependent cytotoxicity (CDC) activity than mAbs derived from Chinese hamster ovary (CHO) cells due to their unique N-glycan structure (lack of core-fucose and non-reducing terminal galactose)...
August 14, 2018: Biochemical and Biophysical Research Communications
Duc Duy Vo, Cécile Becquart, Thi Phuong Anh Tran, Audrey Di Giorgio, Fabien Darfeuille, Cathy Staedel, Maria Duca
MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that regulate gene expression at the post-transcriptional level. Accumulating evidence indicates that miRNAs are aberrantly expressed in a variety of human cancers, thus being oncogenic. The inhibition of oncogenic miRNAs (defined as the blocking of miRNAs' production or function) would find application in the therapy of different types of cancer in which these miRNAs are implicated. In this work, we describe the design and synthesis of new small-molecule RNA ligands with the aim of inhibiting Dicer-mediated processing of oncogenic miRNAs...
August 17, 2018: Organic & Biomolecular Chemistry
Arpita Ghosh, Natalya Degyatoreva, Casey Kukielski, Sandra Story, Sayantan Bhaduri, Krishnagopal Maiti, Smita Nahar, Arjun Ray, Dev P Arya, Souvik Maiti
Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose cell polarity and cell-cell adhesion and gain migratory and invasive properties to become mesenchymal cells that are very vital for development, wound healing and stem cell behavior and contribute pathologically to fibrosis and cancer progression. miR21, a potent regulator of the tumor suppressor gene PTEN, can be silenced to reverse EMT, thereby providing an attractive target for abrogating the malignant behavior of breast cancer...
July 1, 2018: MedChemComm
Liang Li, Lei Hu, Chunyanzhao Zhao, Sheng-Hua Zhang, Rong Wang, Yi Li, Rong-Guang Shao, Yongsu Zhen
Depending on increasing extracellular proteins utilization and altering metabolic programs, cancer cell could proliferate and survive unrestrictedly by ingesting human serum albumin (HSA) to serve as nutritional amino acids. Here, we hypothesize that the consumption of albumin by cancer cells could be utilized as an efficient approach to targeted drug delivery. Lidamycin (LDM), an antitumor antibiotic with extremely potent cytotoxicity to cultured cancer cells, consists of an apoprotein (LDP) and an active enediyne chromophore (AE)...
August 14, 2018: Bioconjugate Chemistry
Nishant S Gandhi, Sudhakar Godeshala, Dana-Lynn T Koomoa-Lange, Bhavani Miryala, Kaushal Rege, Mahavir B Chougule
PURPOSE: Lung cancer is one of the leading causes of deaths in the United States, but currently available therapies for lung cancer are associated with reduced efficacy and adverse side effects. Small interfering RNA (siRNA) can knock down the expression of specific genes and result in therapeutic efficacy in lung cancer. Recently, mTOR siRNA has been shown to induce apoptosis in NSCLC cell lines but its use is limited due to poor stability in biological conditions. METHODS: In this study, we modified an aminoglyocisde-derived cationic poly (amino-ether) by introducing a thiol group using Traut's reagent to generate a bio-reducible modified-poly (amino-ether) (mPAE)...
August 13, 2018: Pharmaceutical Research
Sungjin Kim, Anuj K Sharma, Olena K Vatamaniuk
The chronic exposure of humans to toxic metals such as cadmium from food and air causes dysfunction of vital organs, neurodegenerative conditions, and cancer. In this regard, members of the ABCB sub-family of the ATP-binding cassette (ABC) transporter superfamily, ABCB6/HMT-1, are acutely required for the detoxification of heavy metals and are present in genomes of many organisms including the nematode worm, Caenorhabditis elegans and humans. We showed previously that C. elegans ABCB6/HMT-1 detoxifies cadmium, copper, and arsenic, and is expressed in liver-like cells, the coelomocytes, head neurons and intestinal cells, which are the cell types that are affected by heavy metal poisoning in humans...
2018: Frontiers in Physiology
Travis B Salisbury, Subha Arthur
The progression of cancer is associated with increases in amino acid uptake by cancer cells. Upon their entry into cells through specific transporters, exogenous amino acids are used to synthesize proteins, nucleic acids and lipids and to generate ATP. The essential amino acid leucine is also important for maintaining cancer-associated signaling pathways. By upregulating amino acid transporters, cancer cells gain greater access to exogenous amino acids to support chronic proliferation, maintain metabolic pathways, and to enhance certain signal transduction pathways...
August 12, 2018: International Journal of Molecular Sciences
Brendan T Finicle, Vaishali Jayashankar, Aimee L Edinger
While cancer cell proliferation depends on access to extracellular nutrients, inadequate tumour perfusion means that glucose, amino acids and lipids are often in short supply. To overcome this obstacle to growth, cancer cells utilize multiple scavenging strategies, obtaining macromolecules from the microenvironment and breaking them down in the lysosome to produce substrates for ATP generation and anabolism. Recent studies have revealed four scavenging pathways that support cancer cell proliferation in low-nutrient environments: scavenging of extracellular matrix proteins via integrins, receptor-mediated albumin uptake and catabolism, macropinocytic consumption of multiple components of the tumour microenvironment and the engulfment and degradation of entire live cells via entosis...
August 10, 2018: Nature Reviews. Cancer
Hoon Choi, Ting Liu, Hui Qiao, Ann-Marie Chacko, Shang-Hsiu Hu, San-Yuan Chen, Rong Zhou, I-Wei Chen
Sub-50 nm nanoparticles feature long circulation and deep tumor penetration. However, at high volume fractions needed for intravenous injection, safe, highly biocompatible phospholipids cannot form such nanoparticles due to the fluidity of phospholipid shells. Here we overcome this challenge using a nano-surfactant, a sterilized 18-amino-acid biomimetic of the amphipathic helical motif abundant in HDL-apolipoproteins. As it induces a nanoscale phase (glass) transition in the phospholipid monolayer, the peptide stabilizes 5-7 nm phospholipid micelles that do not fuse at high concentrations but aggregate into stable micellesomes exhibiting size-dependent penetration into tumors...
July 30, 2018: Biomaterials
Fanwen Wang, Caoying Xu, Renhao Peng, Bin Li, Xutong Shen, Heng Zheng, Xingzhen Lao
Thymosin α1 (Tα1), a hormone containing 28 amino acids, has been approved in several cancer therapies, but the lack of tumor-targeting hinders its full use in tumor treatment. We designed a new peptide by connecting Tα1 and RGDR, generating a product, Tα1-RGDR, where RGDR is located in the C-end with both tumor-homing and cell internalizing properties (C-end rule peptides, a consensus R/KXXR/K motif). This work aimed to study the antitumor and immunological activities of Tα1-RGDR, and its differences compared with the wild-type Tα1...
August 7, 2018: Biochimie
Normann Steiner, Udo Müller, Roman Hajek, Sabina Sevcikova, Bojana Borjan, Karin Jöhrer, Georg Göbel, Andreas Pircher, Eberhard Gunsilius
INTRODUCTION: Multiple myeloma (MM), a malignant plasma cell disorder, is still an incurable disease. Thus, the identification of novel therapeutic targets is of utmost importance. Here, we evaluated the peripheral blood-based metabolic profile of patients with MM. MATERIAL & METHODS: Peripheral blood plasma levels of 188 endogenous metabolites, including amino acids, biogenic amines, acylcarnitines, glycerophospholipids, sphingomyelins, and hexoses were determined in patients with plasma cell dyscrasias: monoclonal gammopathy of undetermined significance, a precursor stage of MM (MGUS, n = 15), newly diagnosed MM, (NDMM, n = 32), relapsed/refractory MM (RRMM, n = 19) and in 25 healthy controls by mass spectrometry...
2018: PloS One
Anna Drabik
Protein glycosylation, as one of the most common and complex posttranslational modifications, plays an important role in many biological processes. Along with the intensive progress in mass spectrometry techniques and development of glycan search tools and databases, glycoproteomics has become a popular subject of studies. The possibility of simultaneous identification of amino acid sequence, glycosylation sites, and glycan composition enabled the monitoring of changes in glycosylation patterns in various pathological states...
August 10, 2018: Proteomics. Clinical Applications
Chen Wang, Ping Wu, Lei Yao, Jinghua Xue, Liangxiong Xu, Hanxiang Li, Wangqiu Deng, Xiaoyi Wei
Four new peptaibiotics, acremotins A-D (1-4) featuring three α,α-dialkylated amino acid-imino acid motifs and an unreduced C-terminal residue, along with the known peptaibiotic XR586 (5) were isolated from the solid cultures of the soil-derived fungus Acremonium persicinum SC0105. Their primary structures were characterized by detailed analysis of the HRESIMS/MS fragmentation pattern combined with comprehensive interpretation of the 1D and 2D NMR spectroscopic data. The absolute configurations of amino acid residues were determined by the advanced Marfey's method...
August 8, 2018: Journal of Antibiotics
S M Gilbert, C J Oliphant, S Hassan, A L Peille, P Bronsert, S Falzoni, F Di Virgilio, S McNulty, R Lara
The ATP-gated receptor P2X7 is expressed in multiple malignant tumours including neuroblastoma, melanoma, prostate, lung and breast. P2X7 has a significant role in mediating diverse cell responses, which upon dysregulation are associated with tumour initiation and development. The rapid, ATP-mediated activation of P2X7 induces a fast-inward cation current in cells. However, prolonged ATP-mediated activation of P2X7 leads to formation of a pore that increases membrane permeability and eventually causes cell death...
August 7, 2018: Oncogene
Joey De Backer, Jamoliddin Razzokov, Dietmar Hammerschmid, Carl Mensch, Zainab Hafideddine, Naresh Kumar, Geert van Raemdonck, Maksudbek Yusupov, Sabine Van Doorslaer, Christian Johannessen, Frank Sobott, Annemie Bogaerts, Sylvia Dewilde
Many current anti-cancer therapies rely on increasing the intracellular reactive oxygen and nitrogen species (RONS) contents with the aim to induce irreparable damage, which subsequently results in tumor cell death. A novel tool in cancer therapy is the use of cold atmospheric plasma (CAP), which has been found to be very effective in the treatment of many different cancer cell types in vitro as well as in vivo, mainly through the vast generation of RONS. One of the key determinants of the cell's fate will be the interaction of RONS, generated by CAP, with important proteins, i...
July 24, 2018: Redox Biology
Saloua Kahla, Samia Hammami, Lotfi Kochbati, Mohamed Badis Chanoufi, Ridha Oueslati
Specific genetic mutations in human papillomavirus type 16 (HPV16) DNA are considered important in cervical lesion progression. This study analyzes to what extent radiotherapy treatment contributes to viral DNA mutation in cervical cell carcinomas, and the biological significance of these mutations. Serial tumor tissue, including 44 cervical cancer samples, collected before and after radiotherapy, and 52 biopsies with benign cervices, were tested and analyzed for the presence of HPV16, and for the integrity of the E2 gene...
August 3, 2018: Infection, Genetics and Evolution
Angelika Bröer, Stephen Fairweather, Stefan Bröer
The glutamine transporter ASCT2 (SLC1A5) is actively investigated as an oncological target, but the field lacks efficient ASCT2 inhibitors. A new group of ASCT2 inhibitors, 2-amino-4-bis(aryloxybenzyl)aminobutanoic acids (AABA), were developed recently and shown to suppress tumor growth in preclinical in vivo models. To test its specificity, we deleted ASCT2 in two human cancer cell lines. Surprisingly, growth of parental and ASCT2-knockout cells was equally sensitive to AABA compounds. AABA compounds inhibited glutamine transport in cells lacking ASCT2, but not in parental cells...
2018: Frontiers in Pharmacology
Ming Huang, Tianyu F Qi, Lin Li, Gao Zhang, Yinsheng Wang
Small GTPases of the Ras superfamily are master regulators of intracellular trafficking and constitute essential signaling components in all eukaryotes. Aberrant small GTPase signaling is associated with a wide spectrum of human diseases including cancer. Here we developed a high-throughput, multiple-reaction monitoring-based workflow coupled with stable isotope labeling by amino acids in cell culture, for targeted quantification of approximately 100 small GTPases in cultured human cells. Using this method, we investigated the differential expression of small GTPases in three pairs of primary and metastatic melanoma cell lines...
August 2, 2018: Cancer Research
Mohammed B Alshammari, Mohammed H Geesi, El Hassane Anouar, Rashad Al-Salahi, Abdulrahman I Alharthi, Yasser Elnakady, Mohamed Marzouk
Twenty-two 2-thiophen-naphtho(benzo)oxazinone derivatives are prepared using 3-amino-2-naphthoic and 5-nitroanthranilic acids as building blocks. The target compounds (1-22) were evaluated quantitatively for their cytotoxic effects in vitro against three cancer cell lines, including the lung A549, the hepatocyte HepG2, and the breast MCF-7 carcinoma cells. Compounds 1, 12, 14, and 21 were found to exhibit remarkable cytotoxicity against the tested cancer cell lines. Compound 21 has shown the highest activity against A549 and MCF-7 (IC50 : 9...
September 2018: Cell Biochemistry and Biophysics
Akito Nakamura, Tadahiro Nambu, Shunsuke Ebara, Yuka Hasegawa, Kosei Toyoshima, Yasuko Tsuchiya, Daisuke Tomita, Jun Fujimoto, Osamu Kurasawa, Chisato Takahara, Ayumi Ando, Ryuichi Nishigaki, Yoshinori Satomi, Akito Hata, Takahito Hara
General control nonderepressible 2 (GCN2) plays a major role in the cellular response to amino acid limitation. Although maintenance of amino acid homeostasis is critical for tumor growth, the contribution of GCN2 to cancer cell survival and proliferation is poorly understood. In this study, we generated GCN2 inhibitors and demonstrated that inhibition of GCN2 sensitizes cancer cells with low basal-level expression of asparagine synthetase (ASNS) to the antileukemic agent l-asparaginase (ASNase) in vitro and in vivo...
August 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
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