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L-Arginine Cancer

Akram Assali, Omid Akhavan, Fatemeh Mottaghitalab, Mohsen Adeli, Rassoul Dinarvand, Shayan Razzazan, Ehsan Arefian, Masoud Soleimani, Fatemeh Atyabi
Introduction: MicroRNA-101 (miR-101) is an intense cancer suppressor with special algorithm to target a wide range of pathways and genes which indicates the ability to regulate apoptosis, cellular stress, metastasis, autophagy, and tumor growth. Silencing of some genes such as Stathmin1 with miR-101 can be interpreted as apoptotic accelerator and autophagy suppressor. It is hypothesized that hybrid microRNA (miRNA) delivery structures based on cationized graphene oxide (GO) could take superiority of targeting and photothermal therapy to suppress the cancer cells...
2018: International Journal of Nanomedicine
Kui Deng, Peng Han, Wei Song, Zhuozhong Wang, Fan Zhang, Hongyu Xie, Weiwei Zhao, Huan Xu, Yuqing Cai, Zhiwei Rong, Xiwen Yu, Bin-Bin Cui, Kang Li
BACKGROUND: Many studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear. METHODS: In this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis...
October 5, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Vineet Sadarangani, Safikur Rahman, Apurba Kumar Sau
Recent studies have highlighted the therapeutic importance of bimetallic human arginase-I against hyperargininemia and L-arginine auxotrophic cancers. The longer retention of catalytic activity of the Co2+ -enzyme than that of the Mn2+ in human serum is associated with its enhanced therapeutic potential. To understand the basis of this and also to explore the role of a bimetallic center as well as the role of individual metal ions in the stability, we performed a detailed biochemical and biophysical investigation...
November 2018: Biochimica et biophysica acta. Proteins and proteomics
Tadashi Yamamuro, Kana Inoue, Yasuki Nagai, Daisuke Azuma, Aya Yamamoto, Kantaro Hara, Masaharu Kohara, Takashi Iwata, Shinichi Nakatsuka, Eiichi Morii, Tsunehiko Yamamoto
Ectopic ACTH syndrome (EAS) is a potentially fatal endocrine disease that results from a variety of neuroendocrine tumors (NETs), such as small cell lung cancer (SCLC) and bronchial typical carcinoid. Typical carcinoid is usually slow growing, not associated with plasma progastrin releasing peptide (ProGRP) elevation. Here, we report a 47-year-old female smoker with progressive typical carcinoid and plasma ProGRP elevation. Several types of Cushingoid features were found on physical examination. In addition, laboratory examination showed elevated plasma ACTH and serum cortisol levels...
September 20, 2018: Endocrine Journal
Waliul Islam, Jun Fang, Takahisa Imamura, Tomáš Etrych, Vladimir Subr, Karel Ulbrich, Hiroshi Maeda
Enhanced permeability and retention (EPR) effect-based nanomedicine is a promising strategy for successful anticancer therapy. The EPR effect is based on tumor blood flow. Because advanced large tumors, as frequently seen in clinical settings, are heterogeneous, with regions of defective vasculature and blood flow, achieving the desired tumor drug delivery is difficult. Here, we utilized the EPR effect to increase drug delivery. To augment the EPR effect for improved therapeutic effects of nanomedicine, we exploited vascular mediators-the nitric oxide (NO) generators nitroglycerin (NG), hydroxyurea, and L-arginine...
September 19, 2018: Molecular Cancer Therapeutics
Pinghua Ling, Caihua Qian, Feng Gao, Jianping Lei
An enzyme-immobilized metal-organic framework (MOF) nanosheet system was developed as a tandem catalyst, which converted glucose into gluconic acid and H2O2, and sequentially the latter could be used to catalyze the oxidation of l-arginine to generate nitric oxide in the presence of porphyrinic MOFs as artificial enzymes under physiological pH, showing great potential in cancer depleting glucose for starving-like/gas therapy.
October 2, 2018: Chemical Communications: Chem Comm
Mia Aaboe Jørgensen, Morten Orebo Holmström, Evelina Martinenaite, Caroline Hasselbalch Riley, Hans Carl Hasselbalch, Mads Hald Andersen
Compelling evidence supports the existence of a profound immune dysregulation in patients with chronic myeloproliferative neoplasms (MPN). Increased Arginase-1 expression has been described in MPN patients and in solid cancers. This increase contributes to an immunosuppressive tumor microenvironment in MPN patients because of L-arginine depletion by Arginase-1-expressing regulatory cells and cancer cells, which subsequently limits the activation of circulating effector cells. In the present study, we demonstrate that Arginase-1-derived peptides are recognized by T cells among peripheral mononuclear blood cells from MPN patients...
2018: Oncoimmunology
Merav D Shmueli, Limor Levy-Kanfo, Esraa Haj, Alan R Schoenfeld, Ehud Gazit, Daniel Segal
The von Hippel-Lindau (VHL) syndrome is a rare inherited cancer, caused by mutations in the VHL gene, many of which render the VHL protein (pVHL) unstable. pVHL is a tumor-suppressor protein implicated in a variety of cellular processes, most notably in response to changes in oxygen availability, due to its role as part of an E3-ligase complex which targets the hypoxia-inducible factor (HIF) for degradation. Previously we reported, using in silico and in vitro analyses, that common oncogenic VHL mutations render pVHL less stable than the wild-type protein, distort its core domain and as a result reduce the ability of the protein to bind its target HIF-1α...
September 7, 2018: Oncogene
Pierre-Jacques Hamard, Gabriel E Santiago, Fan Liu, Daniel L Karl, Concepcion Martinez, Na Man, Adnan K Mookhtiar, Stephanie Duffort, Sarah Greenblatt, Ramiro E Verdun, Stephen D Nimer
Protein arginine methyltransferase 5 (PRMT5) is overexpressed in many cancer types and is a promising therapeutic target for several of them, including leukemia and lymphoma. However, we and others have reported that PRMT5 is essential for normal physiology. This dependence may become dose limiting in a therapeutic setting, warranting the search for combinatorial approaches. Here, we report that PRMT5 depletion or inhibition impairs homologous recombination (HR) DNA repair, leading to DNA-damage accumulation, p53 activation, cell-cycle arrest, and cell death...
September 4, 2018: Cell Reports
Ziye Dong, Dan Yu, Qingye Liu, Zhenya Ding, Veronica J Lyons, Robert K Bright, Dimitri Pappas, Xinli Liu, Wei Li
Self-floating hollow glass microspheres (HGMS) modified with tumor-specific antibodies have been developed for the capture of circulating tumor cells (CTCs), and have demonstrated effective cell isolation and good viability of isolated cancer cells. However, the capture efficiency decreases dramatically if the spiked cell concentration is low, possibly due to insufficient interactions between cancer cells and the HGMS surface. In order to apply HGMS-based CTC isolation to clinically relevant samples, it is desirable to create nanostructures on the surface of HGMS to enhance cell-surface interactions...
September 13, 2018: Nanoscale
Jingjing Yao, Zhenhua Du, Zibo Li, Shuhui Zhang, Yukun Lin, Haiyun Li, Lin Zhou, Yuehua Wang, Guixi Yan, Xianchuang Wu, Yongjian Duan, Gangjun Du
6-Gingerol (6-G) is the main bioactive component in Ginger (Zingiber officinale Roscoe). The aim of this study was to explore the contribution of macrophage polarization in 6-G-associated anti-cancer effects. In a urethane-induced lung carcinogenic model, lung carcinogenesis was positively correlated with macrophage (F4/80+) infiltration in lung interstitial in the control group. Furthermore, higher numbers of arginase+/F4/80+ M2 cells than iNOS+/F4/80+ M1 cells were observed in interstitial macrophages. Moreover, macrophage depletion by liposome-encapsulated clodronate (LEC) could significantly prevent lung carcinogenesis, whereas pexidartinib promoted lung carcinogenesis...
September 19, 2018: Food & Function
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 1, 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...
October 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 Oses-Prieto, Hongjun Wang, Olan Jackson-Weaver, Tingwei Zhang, Samy Lamouille, Jian Wu, Alma 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 transforming growth factor β (TGF-β) drives this program in cooperation with other signaling pathways and through TGF-β-activated SMAD3 as the 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)...
August 24, 2018: Journal of Biological Chemistry
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