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https://www.readbyqxmd.com/read/28641473/co-targeting-intracellular-ph-and-essential-amino-acid-uptake-cooperates-to-induce-cell-death-of-t-all-ll-cells
#1
Véronique Imbert, Marielle Nebout, Didier Mary, Hitoshi Endou, Michael F Wempe, Claudiu T Supuran, Jean-Yves Winum, Jean-François Peyron
Cancer cells reprogram their metabolism to optimize their growth and proliferation in the host microenvironment. For this purpose, they enhance the uptake of extracellular nutrients and deal with the metabolic waste products through the overexpression of numerous membrane proteins including amino-acid transporters (LAT1) and acid-base regulating enzymes, such as carbonic anhydrases (CAs). Here we describe the anti-tumoral effects of a new class of CAXII inhibitors, the glycosyl coumarins on T-ALL/LL cells. These effects appeared to be mediated through inhibition of mTOR/Akt pathway and c-myc downregulation...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28611768/innate-immunity-and-breast-milk
#2
REVIEW
Nicole Theresa Cacho, Robert M Lawrence
Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611276/vitamin-k-and-its-analogs-potential-avenues-for-prostate-cancer-management
#3
REVIEW
Subramanyam Dasari, Syed M Ali, Guoxing Zheng, Aoshuang Chen, Venkata Satish Dontaraju, Maarten C Bosland, Andre Kajdacsy-Balla, Gnanasekar Munirathinam
Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28606221/dietary-inflammatory-index-before-diagnosis-and-survival-in-an-italian-cohort-of-women-with-breast-cancer
#4
Antonella Zucchetto, Diego Serraino, Nitin Shivappa, James R Hébert, Carmen Stocco, Antonella Puppo, Fabio Falcini, Chiara Panato, Luigino Dal Maso, Jerry Polesel
The dietary inflammatory indexTM (DII) has been shown to correlate with concentrations of several inflammatory markers and a variety of chronic disease endpoints, including cancers of various anatomic sites. We investigated whether the DII was associated with the risk for death among women with breast cancer (BrCa). This retrospective cohort study included 1453 women with BrCa, diagnosed between 1990 and 1994, and previously enrolled in a case-control study in northern Italy. With a median follow-up of 12·6 years, we observed 503 deaths, among which 398 were due to BrCa...
June 13, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28601430/imiquimod-induced-autophagy-is-regulated-by-er-stress-mediated-pkr-activation-in-cancer-cells
#5
Shu-Hao Chang, Shi-Wei Huang, Sin-Ting Wang, Kai-Cheng Chung, Chia-Wei Hsieh, Jun-Kai Kao, Yi-Ju Chen, Chun-Ying Wu, Jeng-Jer Shieh
BACKGROUND: Autophagy is a highly conserved cellular catabolic pathway for degradation and recycling of intracellular components in response to nutrient starvation or environmental stress. Endoplasmic reticulum (ER) homeostasis can be disturbed by physiological and pathological influences, resulting in accumulation of misfolded and unfolded proteins in the ER lumen, a condition referred to as ER stress. Imiquimod (IMQ), a Toll-like receptor (TLR) 7 ligand, possesses anti-tumor and anti-viral activities in vitro and in vivo...
May 2, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28590932/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#6
Tzu-Wei Lin, Ming-Teh Chen, Liang-Tin Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28580313/the-effect-of-inflammatory-status-on-butyrate-and-folate-uptake-by-tumoral-caco-2-and-non-tumoral-iec-6-intestinal-epithelial-cells
#7
Mafalda R Couto, Pedro Gonçalves, Telmo A Catarino, Fátima Martel
OBJECTIVE: Colorectal cancer (CRC) is the second leading cause of cancer death in occidental countries. Chronic inflammatory bowel disease (crohn's disease and ulcerative colitis) is associated with an increased risk for CRC development. The aim of this work was to investigate the relationship between inflammatory status and absorption of nutrients with a role in CRC pathogenesis. MATERIALS AND METHODS: In this experimental study, we evaluated the in vitro effect of tumour necrosis factor-alpha (TNF-α), interferon-γ (IF-γ), and acetylsalicylic acid on 14C-butyrate (14C- BT), 3H-folic acid (3H-FA) uptake, and on proliferation, viability and differentiation of Caco-2 and IEC-6 cells in culture...
2017: Cell Journal
https://www.readbyqxmd.com/read/28577085/endoplasmic-reticulum-stress-regulates-tumor-growth-and-anti-tumor-immunity-a-promising-opportunity-for-cancer-immunotherapy
#8
REVIEW
Eslam Mohamed, Yu Cao, Paulo C Rodriguez
The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes...
June 2, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28543172/nanoparticles-as-new-tools-for-inhibition-of-cancer-angiogenesis
#9
REVIEW
Nasser Hashemi Goradel, Farshid Ghiyami-Hour, Samira Jahangiri, Babak Negahdari, Amirhossein Sahebkar, Aria Masoudifar, Hamed Mirzaei
Angiogenesis is known as one of the hallmarks of cancer. Multiple lines evidence indicated that vascular endothelium growth factor (VEGF) is a key player in the progression of angiogenesis and exerts its functions via interaction with tyrosine kinase receptors (TKRs). These receptors could trigger a variety of cascades that lead to the supply of oxygen and nutrients to tumor cells and survival of these cells. With respect to pivotal role of angiogenesis in the tumor growth and survival, finding new therapeutic approaches via targeting angiogenesis could open a new horizon in cancer therapy...
May 25, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28539838/andrographolide-inhibits-angiogenesis-by-inhibiting-the-mir-21-5p-timp3-signaling-pathway
#10
Jianwei Dai, Yuyin Lin, Youfa Duan, Zixuan Li, Dalei Zhou, Wensheng Chen, Lijing Wang, Qian-Qian Zhang
Angiogenesis provides nutrients and oxygen to promote tumor growth and affords a channel that facilitates tumor cell entry into the circulation. Andrographolide (Andro) possess anti-tumor activity; however, its direct effect on angiogenesis still needs to be clarified. In this study, our experiments revealed that Andro significantly inhibited vascular growth in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumor angiogenesis was also suppressed by Andro. Additionally, we found that cell proliferation, migration and tube formation of vascular endothelial cells was inhibited by Andro treatment in vitro...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28538141/cancer-cell-and-macrophage-cross-talk-in-the-tumor-microenvironment
#11
REVIEW
Nathalie Dehne, Javier Mora, Dmitry Namgaladze, Andreas Weigert, Bernhard Brüne
Tumors are composed of tumor cells, nonmalignant cells, and the vascular system. Among them is intense communication via cell-cell contact-dependent mechanisms and/or soluble messengers. In the tumor microenvironment cells often face a certain degree of oxygen and nutrient deprivation. Hypoxic stress alters the metabolism of tumor cells but also of macrophages, as one dominating immune cell population in most solid tumors, with subsequent changes in the microenvironment. This alters the phenotype and metabolism of macrophages, to induce a tumor-promoting reprogramming...
May 21, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28528980/phospholipase-c-%C3%AE-1-negatively-regulates-autophagy-in-colorectal-cancer-cells
#12
Makoto Shimozawa, Sakiho Anzai, Reiko Satow, Kiyoko Fukami
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Kirsten rat sarcoma viral oncogene homolog (KRAS) is frequently mutated in CRC, and KRAS mutations promote cell motility, growth, and survival. We previously revealed that the expression of phospholipase C (PLC) δ1, one of the most basal PLCs, is down-regulated in colon adenocarcinoma, and that the KRAS signaling pathway suppresses PLCδ1 expression. Although recent studies revealed that KRAS mutations activate autophagy in cancer cells, a relation between PLCδ1 and autophagy remains unclear...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28503088/restoring-trail-induced-apoptosis-using-naturopathy-hercules-joins-hand-with-nature-to-triumph-over-lernaean-hydra
#13
REVIEW
Ammad Ahmad Farooqi, Cosmo Damiano Gadaleta, Girolamo Ranieri, Sundas Fayyaz, Ilaria Marech
Cancer is a multifaceted disease. Our deepened knowledge about genetic and biological mechanisms of cancer cells presents an opportunity to explore the inter-individual differences in the body's ability to metabolize and respond to different nutrients. It is becoming progressively more understandable that the deregulation of several signaling pathways and the alterations in apoptotic response are some of the major determinants that underpin carcinogenesis. Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL)-mediated signaling has gained a remarkable appreciation because of its ability to selectively induce apoptosis in cancer cells leaving normal cells intact...
February 2017: Current Genomics
https://www.readbyqxmd.com/read/28492544/halofuginone-dually-regulates-autophagic-flux-through-nutrient-sensing-pathways-in-colorectal-cancer
#14
Guo-Qing Chen, Rui-Hong Gong, Da-Jian Yang, Ge Zhang, Ai-Ping Lu, Siu-Cheong Yan, Shu-Hai Lin, Zhao-Xiang Bian
Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28489075/lipoprotein-biomimetic-nanostructure-enables-efficient-targeting-delivery-of-sirna-to-ras-activated-glioblastoma-cells-via-macropinocytosis
#15
Jia-Lin Huang, Gan Jiang, Qing-Xiang Song, Xiao Gu, Meng Hu, Xiao-Lin Wang, Hua-Hua Song, Le-Pei Chen, Ying-Ying Lin, Di Jiang, Jun Chen, Jun-Feng Feng, Yong-Ming Qiu, Ji-Yao Jiang, Xin-Guo Jiang, Hong-Zhuan Chen, Xiao-Ling Gao
Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma...
May 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28486399/assessment-of-heparanase-mediated-angiogenesis-using-microvascular-endothelial-cells-identification-of-%C3%AE-carrageenan-derivative-as-a-potent-anti-angiogenic-agent
#16
Nicolas Poupard, Pamela Badarou, Fabienne Fasani, Hugo Groult, Nicolas Bridiau, Frédéric Sannier, Stéphanie Bordenave-Juchereau, Claudine Kieda, Jean-Marie Piot, Catherine Grillon, Ingrid Fruitier-Arnaudin, Thierry Maugard
Heparanase is overexpressed by tumor cells and degrades the extracellular matrix proteoglycans through cleavage of heparan sulfates (HS), allowing pro-angiogenic factor release and thus playing a key role in tumor angiogenesis and metastasis. Here we propose new HS analogs as potent heparanase inhibitors: Heparin as a positive control, Dextran Sulfate, λ-Carrageenan, and modified forms of them obtained by depolymerization associated to glycol splitting (RD-GS). After heparanase activity assessment, 11 kDa RD-GS-λ-Carrageenan emerged as the most effective heparanase inhibitor with an IC50 of 7...
May 9, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28480405/potential-administration-of-lipoic-acid-and-coenzyme-q-against-adipogensis-target-for-weight-reduction
#17
Maryam A Al-Ghamdi, Hani Choudhry, Huda A Al-Doghather, Etimad H Huwait, Taha A Kumosani, Said S Moselhy
BACKGROUND: Body overweight and obesity were considered as a risk factor for many systemic diseases as diabetic hypertension, cardiovascular diseases, and some cancers. The lipoic acid and Co Q are considered as coenzymes needed for enhancement metabolic rate. The goal of this study is to evaluate the anti-obese effect of lipoic acid alone or combined with Co-Q in rats. MATERIALS AND METHODS: Ninety male albino rats (100-150g) were used in this study, divided into six groups (15 each)...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28461484/protein-mediated-viral-latency-is-a-novel-mechanism-for-merkel-cell-polyomavirus-persistence
#18
Hyun Jin Kwun, Yuan Chang, Patrick S Moore
Viral latency, in which a virus genome does not replicate independently of the host cell genome and produces no infectious particles, is required for long-term virus persistence. There is no known latency mechanism for chronic small DNA virus infections. Merkel cell polyomavirus (MCV) causes an aggressive skin cancer after prolonged infection and requires an active large T (LT) phosphoprotein helicase to replicate. We show that evolutionarily conserved MCV LT phosphorylation sites are constitutively recognized by cellular Fbw7, βTrCP, and Skp2 Skp-F-box-cullin (SCF) E3 ubiquitin ligases, which degrade and suppress steady-state LT protein levels...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28452959/anti-inflammatory-mechanism-involved-in-pomegranate-mediated-prevention-of-breast-cancer-the-role-of-nf-%C3%AE%C2%BAb-and-nrf2-signaling-pathways
#19
Animesh Mandal, Deepak Bhatia, Anupam Bishayee
Pomegranate (Punica granatum L.), a nutrient-rich unique fruit, has been used for centuries for the prevention and treatment of various inflammation-driven diseases. Based on our previous study, a characterized pomegranate emulsion (PE) exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms. The objective of the present work is to investigate the anti-inflammatory mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2)...
April 28, 2017: Nutrients
https://www.readbyqxmd.com/read/28445144/stroma-derived-hgf-drives-metabolic-adaptation-of-colorectal-cancer-to-angiogenesis-inhibitors
#20
Alessia Mira, Virginia Morello, Maria Virtudes Céspedes, Timothy Perera, Paolo M Comoglio, Ramon Mangues, Paolo Michieli
The role of paracrine Hepatocyte Growth Factor (HGF) in the resistance to angiogenesis inhibitors (AIs) is hidden in xenograft models because mouse HGF fails to fully activate human MET. To uncover it, we compared the efficacy of AIs in wild-type and human HGF knock-in SCID mice bearing orthotopic human colorectal tumors. Species-specific HGF/MET signaling dramatically impaired the response to anti-angiogenic agents and boosted metastatic dissemination. In cell-based assays mimicking the consequences of anti-angiogenic therapy, colorectal cancer cells were completely resistant to hypoxia but extremely sensitive to nutrient deprivation...
June 13, 2017: Oncotarget
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