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L-Arginine Cancer

Hsiao P J Voon, Maheshi Udugama, Wendi Lin, Linda Hii, Ruby H P Law, David L Steer, Partha P Das, Jeffrey R Mann, Lee H Wong
An array of oncogenic histone point mutations have been identified across a number of different cancer studies. It has been suggested that some of these mutant histones can exert their effects by inhibiting epigenetic writers. Here, we report that the H3.3 G34R (glycine to arginine) substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induced chromatin alterations that were comparable to a KDM4 A/B/C triple-knockout...
August 7, 2018: Nature Communications
Ping Ye, Haitao Yin, Xuelian Gu, Yuanyuan Ye, Qingxiao Zhao, Zhaohua Chang, Baosan Han, Xiaoxiang Chen, Peifeng Liu
AIM: Current cryoablation therapy easily induces a high tumor recurrence, it is therefore necessary to develop an effective method to enhance its antitumor efficacy. MATERIALS & METHODS: We solve the aforementioned problem by introducing doxorubicin (DOX) loading methoxy polyethylene glycol-polylactic-co-glycolic acid-poly-L-lysine-cyclic arginine-glycine-aspartic acid peptide nanoparticles (DOX nanoparticles) in the process of cryoablation. RESULTS: The combination of cryoablation and DOX nanoparticles greatly decreases the recurrence rate of breast cancer, which is owing to the specific targeting therapy of DOX nanoparticles for residuary breast cancer cells after cryoablation...
August 3, 2018: Nanomedicine
Sanaa Ben Djemaa, Stephanie David, Katel Hervé-Aubert, Annarita Falanga, Stefania Galdiero, Emilie Allard-Vannier, Igor Chourpa, Emilie Munnier
The development of an efficient small interfering RNA (siRNA) delivery system has held scientists interest since the discovery of the RNA interference mechanism (RNAi). This strategy gives hope for the treatment of many severe diseases. Herein, we developed hybrid nanovectors able to deliver siRNA to triple negative breast cancer cells. The nanovectors are based on PEGylated superparamagnetic iron oxide nanoparticles (SPION) functionalized with gH625 peptide, chitosan and poly-L-arginine. Every component has a key role and specific function: SPION is the core scaffolding the nanovector; PEG participates in the colloidal stability and the immune stealthiness; gH625 peptide promotes the nanovector internalization into cancer cells; cationic polymers provide the siRNA protection and favor siRNA endosomal escape and delivery to cytosol...
July 28, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Seiji Fujigaki, Shin Nishiumi, Takashi Kobayashi, Makoto Suzuki, Takao Iemoto, Takashi Kojima, Yoshinori Ito, Hiroyuki Daiko, Ken Kato, Hirokazu Shouji, Kazufumi Honda, Takeshi Azuma, Masaru Yoshida
AIM: To identify the serum metabolomics signature that is correlated with the chemoradiosensitivity of esophageal squamous cell carcinoma (ESCC). MATERIALS & METHODS: Untargeted and targeted metabolomics analysis of serum samples from 26 ESCC patients, which were collected before the neoadjuvant chemoradiotherapy, was performed. RESULTS: On receiving the results of untargeted metabolomics analysis, we performed the targeted metabolomics analysis of the six metabolites (arabitol, betaine, glycine, L-serine, L-arginine and L-aspartate)...
August 2018: Biomarkers in Medicine
Md Sajid Ghufran, Priyanka Soni, Santosh R Kanade
Aflatoxins are fungal metabolites classified into four major groups such as B1 , B2 , G1 , and G2 . These natural aflatoxins are designated as group I carcinogen by the International Agency for Research on Cancer. Among these, the aflatoxin B1 is more potent. Protein arginine methyltransferase 5, an epigenetic modulator, emerged as an oncoprotein, is overexpressed in diverse forms of cancers. The present study aims to explore the AFB1 -mediated overexpression of PRMT5. The AFB1 at nanomolar concentrations increased the cell viability, as well as the expression of PRMT5 and its binding partner methylosome protein 50 level significantly in L-132 and HaCaT cells...
July 6, 2018: Cell Biology and Toxicology
Manoj Nepal, Chi Ma, Guoxiang Xie, Wei Jia, Peiwen Fei
Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA...
June 21, 2018: Aging
Srinidi Mohan, Seema Patel, Ian Greenstein, Cathy Ng, Kelly Frazier, Giang Nguyen, Lisa Harding, David Barlow
We had shown Nw -hydroxy-L-arginine (NOHA) as a promising blood-based biomarker for estrogen-receptor-negative (ER - ) breast cancer (BC) that differentiates ER - BC based on grade and molecular phenotype. In this in vitro study, we assessed the metabolic relevance for ER- BC-specific NOHA modulation and correlated them with NOHA regulatory responses. This study aids future NOHA clinical utility in ER- BC diagnosis and therapy management and would prove useful for potential drug discovery and development process...
June 20, 2018: Amino Acids
A Loras, M Trassierra, D Sanjuan-Herráez, M C Martínez-Bisbal, J V Castell, G Quintás, J L Ruiz-Cerdá
Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period...
June 15, 2018: Scientific Reports
Yoko Katsuno, Jian Qin, Juan A Oses-Prieto, Hongjun Wang, Olan Jackson-Weaver, Tingwei Zhang, Samy Lamouille, Jian Wu, A L L Burlingame, Jian Xu, Rik Derynck
The epithelial-to-mesenchymal transdifferentiation (EMT) is crucial for tissue differentiation in development, and drives essential steps in cancer and fibrosis. EMT is accompanied by reprogramming of gene expression, and has been associated with the epithelial stem cell state in normal and carcinoma cells. The cytokine TGF-β drives this program in cooperation with other signaling pathways and through TGF-β-activated Smad3 as major effector. TGF-β-induced Smad3 activation is inhibited by Smad7 and to a lesser extent by Smad6, and Smad6 and Smad7 both inhibit Smad1 and Smad5 activation in response to the TGF-β-related bone morphogenetic proteins (BMPs)...
June 15, 2018: Journal of Biological Chemistry
Akram Assali, Omid Akhavan, Mohsen Adeli, Shayan Razzazan, Rassoul Dinarvand, Saeid Zanganeh, Masoud Soleimani, Meshkat Dinarvand, Fatemeh Atyabi
Recent insights into the nanomedicine have revealed that nanoplatforms enhance the efficacy of carrier in therapeutic applications. Here, multifunctional nanoplatforms were utilized in miRNA-101 delivery and NIR thermal therapy to induce apoptosis in breast cancer cells. Au nanorods (NRs) or nanospheres (NSs) covered with graphene oxide (GO) were prepared and functionalized with polyethylene glycol as a stabilizer and poly-L-arginine (P-L-Arg) as a targeting agent. In nanoplatforms, coupling Au@GO prepared stable structures with higher NIR reactivity...
August 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Oliver Schilling, Martin L Biniossek, Bettina Mayer, Brigitta Elsässer, Hans Brandstetter, Peter Goettig, Ulf-Håkan Stenman, Hannu Koistinen
In humans, three different trypsin-isoenzymes have been described. Of these, trypsin-3 appears to be functionally different from the others. In order to systematically study the specificity of the trypsin-isoenzymes, we utilized proteome-derived peptide libraries and quantitative proteomics. We found similar specificity profiles dominated by the well-characterized preference for cleavage after lysine and arginine. Especially, trypsin-1 slightly favored lysine over arginine in this position, while trypsin-3 did not discriminate between them...
June 20, 2018: Biological Chemistry
C Ma, H Tsai, W Su, L Sun, Y Shih, J Wang
Background: Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. Materials and Methods: This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery...
July 2018: Journal of Postgraduate Medicine
Alexandra A P Mansur, Sandhra M Carvalho, Zélia I P Lobato, Maria de Fátima Leite, Armando da Silva Cunha, Herman S Mansur
Polymer-drug conjugation is an attractive approach for target delivering insoluble and highly toxic drugs to tumor sites to overcome the side-effects caused by cancer chemotherapy. In this study we designed and synthesized novel polymer-drug-peptide conjugates for improved specificity on targeting cancer cells. Chemically modified polysaccharide, carboxymethylcellulose (CMC), was conjugated with doxorubicin (DOX) anticancer drug by amide bonds and dually biofunctionalized with integrin-target receptor tripeptide (RGD) and l-arginine (R) as cell-penetrating amino acid for synergistic targeting and enhancing internalization by cancer cells...
June 20, 2018: Bioconjugate Chemistry
Bergljót Magnadóttir, Polly Hayes, Berglind Gísladóttir, Birkir Þór Bragason, Mariya Hristova, Anthony P Nicholas, Sigríður Guðmundsdóttir, Sigrun Lange
Pentraxins are fluid phase pattern recognition molecules that form an important part of the innate immune defence and are conserved between fish and human. In Atlantic cod (Gadus morhua L.), two pentraxin-like proteins have been described, CRP-I and CRP-II. Here we show for the first time that these two CRP forms are post-translationally deiminated (an irreversible conversion of arginine to citrulline) and differ with respect to tissue specific localisation in cod ontogeny from 3 to 84 days post hatching. While both forms are expressed in liver, albeit at temporally differing levels, CRP-I shows a strong association with nervous tissue while CRP-II is strongly associated to mucosal tissues of gut and skin...
October 2018: Developmental and Comparative Immunology
Bin Zhang, Bang-Ce Ye
5-Aminolevulinic acid (ALA) is a non-protein amino acid with a significant potential for cancer treatment and plant stress resistance. Microbial fermentation has gradually replaced the traditional chemical-based method for ALA production, thus increasing the need for high-ALA-producing strains. In this study, we engineered the glutamate producing strain, Corynebacterium glutamicum S9114, for ALA production. To efficiently convert l-glutamate to ALA, hemA and hemL from Salmonella typhimurium and Escherichia coli were tandemly overexpressed...
May 2018: 3 Biotech
Yang Won Min, Eun-Ju Ko, Ji-Yeon Lee, Poong-Lyul Rhee
To explore the pathogenic mechanism of diabetic gastropathy, we investigated differences in response to electrical field stimulation (EFS) of gastric muscles from diabetic and non-diabetic (control) patients. Gastric specimens were obtained from 34 patients and 45 controls who underwent gastrectomy for early gastric cancer. Using organ bath techniques, we examined peak and nadir values of contraction under EFS. To examine responses to purinergic and nitrergic inhibition without cholinergic innervation, atropine, MRS2500, and N-nitro-L-arginine (L-NNA) were added sequentially to the organ bath...
May 8, 2018: Scientific Reports
Bethany Cheree Prudner, Fangdi Sun, Jeffrey Charles Kremer, Jinbin Xu, Chaofeng Huang, Kiran Kumar Solingapuram Sai, Zachary Morgan, Hayden Leeds, Jonathan McConathy, Brian Andrew Van Tine
Rational : In a subset of cancers, arginine auxotrophy occurs due to the loss of expression of argininosuccinate synthetase 1 (ASS1). This loss of ASS1 expression makes cancers sensitive to arginine starvation that is induced by PEGylated arginine deiminase (ADI-PEG20). Although ADI-PEG20 treatment is effective, it does have important limitations. Arginine starvation is only beneficial in patients with cancers that are ASS1-deficient. Also, these tumors may metabolically reprogram to express ASS1, transforming them from an auxotrophic phenotype to a prototrophic phenotype and thus rendering ADI-PEG20 ineffective...
2018: Theranostics
Jingjie Li, Lihuan Guan, Huizhen Zhang, Yue Gao, Jiahong Sun, Xiao Gong, Dongshun Li, Pan Chen, Xiaoyan Liang, Min Huang, Huichang Bi
BACKGROUND: The sensitivity and specificity of non-invasive diagnostic methods for endometriosis, especially at early stages, are not optimal. The clinical diagnostic indicator cancer antigen 125 (CA125) performs poorly in the diagnosis of minimal endometriosis, with a sensitivity of 24%. Therefore, it is urgent to explore novel diagnostic biomarkers. We evaluated the metabolomic profile variation of the eutopic endometrium between minimal-mild endometriosis patients and healthy women by ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)...
April 30, 2018: Reproductive Biology and Endocrinology: RB&E
Dalton L Schiessel, Vickie E Baracos
Cancer-associated malnutrition is driven by reduced dietary intake and by underlying metabolic changes (such as inflammation, anabolic resistance, proteolysis, lipolysis and futile cycling) induced by the tumour and activated immune cells. Cytotoxic and targeted chemotherapies also elicit proteolysis and lipolysis at the tissue level. In this review, we summarise specific mediators and chemotherapy effects that provoke excess proteolysis in muscle and excess lipolysis in adipose tissue. A nutritionally relevant question is whether and to what degree these catabolic changes can be reversed by nutritional therapy...
April 30, 2018: Proceedings of the Nutrition Society
Natesh Singh, Gerhard F Ecker
The large neutral amino acid transporter 1 (LAT1, or SLC7A5) is a sodium- and pH-independent transporter, which supplies essential amino acids (e.g., leucine, phenylalanine) to cells. It plays an important role at the Blood⁻Brain Barrier (BBB) where it facilitates the transport of thyroid hormones, pharmaceuticals (e.g., l-DOPA, gabapentin), and metabolites into the brain. Moreover, its expression is highly upregulated in various types of human cancer that are characterized by an intense demand for amino acids for growth and proliferation...
April 24, 2018: International Journal of Molecular Sciences
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