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https://www.readbyqxmd.com/read/28651060/mechanism-underlying-methyl-eugenol-attenuation-of-intestinal-ischemia-reperfusion-injury
#1
Hanan Saleh, Haidan M El-Shorbagy
Intestinal Ischemia/Reperfusion injury (I/R) is associated with a high risk of mortality in the clinical situation. Many factors are involved in I/R including reactive oxygen species (ROS), cytokine release and apoptosis. We aimed to determine whether a pure methyl eugenol (ME) given before intestinal ischemia, protects against intestinal I/R and the possible mechanism involved in this protection. Rat received ME (100 mg/kg) for 30 days then underwent intestinal I/R with 30 min ischemia and 60 min reperfusion...
June 26, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28649248/a-combination-of-podophyllotoxin-and-rutin-alleviates-radiation-induced-pneumonitis-and-fibrosis-through-modulation-of-lung-inflammation-in-mice
#2
Savita Verma, Bhargab Kalita, Sania Bajaj, Hridayesh Prakash, Ajay Kumar Singh, Manju Lata Gupta
Pneumonitis and pulmonary fibrosis are predominant consequences of radiation exposure, whether planned or accidental. The present study, demonstrates radioprotective potential of a formulation, prepared by combining podophyllotoxin and rutin (G-003M), in mice exposed to 11 Gy thoracic gamma radiation (TGR). Treated mice were observed for survival and other symptomatic features. Formation of reactive oxygen species (ROS)/nitric oxide (NO) was measured in bronchoalveolar lavage cells. DNA damage and cell death were assessed in alveolar cells by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28649131/blocking-the-utilization-of-glucose-induces-the-switch-from-senescence-to-apoptosis-in-pseudolaric-acid-b-treated-human-lung-cancer-cells-in-vitro
#3
Guo-Dong Yao, Jing Yang, Xiu-Xiu Li, Xiao-Yu Song, Toshihiko Hayashi, Shin-Ichi Tashiro, Satoshi Onodera, Shao-Jiang Song, Takashi Ikejima
Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi Gordon, exerts anti-tumor effects in several cancer cell lines. Our previous study showed that PAB mainly induced senescence via p53-p21 activation rather than apoptosis in suppression of the growth of human lung cancer A549 cells (p53 wild-type). In p53-null human lung cancer H1299 cells, however, PAB caused apoptosis without senescence. In this study we investigated what mechanism was responsible for the switch from senescence to apoptosis in PAB-treated human lung cancer cell lines...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28646020/mcam-mediates-chemoresistance-in-small-cell-lung-cancer-via-the-pi3k-akt-sox2-signaling-pathway
#4
Satyendra C Tripathi, Johannes F Fahrmann, Muge Celiktas, Mitzi Aguilar, Kieren D Marini, Mohit Kumar Jolly, Hiroyuki Katayama, Hong Wang, Eunice N Murage, Jennifer B Dennison, D Neil Watkins, Herbert Levine, Edwin J Ostrin, Ayumu Taguchi, Samir M Hanash
Despite favorable responses to initial therapy, small cell lung cancer (SCLC) relapse occurs within a year and exhibits resistance to multiple drugs. Due to limited accessibility of patient tissues for research purposes, SCLC-patient derived xenografts (PDX) have provided the best opportunity to address this limitation. Here we sought to identify novel mechanisms involved in SCLC chemoresistance. Through in-depth proteomic profiling, we identified MCAM as a markedly upregulated surface receptor in chemoresistant SCLC cell lines and in chemoresistant PDX compared to matched treatment-naïve tumors...
June 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28643510/characterization-of-the-saffron-derivative-crocetin-as-an-inhibitor-of-human-lactate-dehydrogenase-5-in-the-antiglycolytic-approach-against-cancer
#5
Carlotta Granchi, Serena Fortunato, Serena Meini, Flavio Rizzolio, Isabella Caligiuri, Tiziano Tuccinardi, Hyang Yeon Lee, Paul J Hergenrother, Filippo Minutolo
Inhibition of lactate dehydrogenase (LDH) represents an innovative approach to tackle cancer because this peculiar glycolytic metabolism is characteristic of most invasive tumor cells. An investigation into the biological properties of saffron extracts led to the discover of their LDH-inhibition properties. In particular, the most important saffron components, crocetin, was found to inhibit LDH (IC50 = 54.9 ± 4.7 µM). This carotenoid was independently produced by chemical synthesis, and its LDH-inhibition properties manifested via its antiproliferative activity against two glycolytic cancer cell lines (A549 and HeLa, IC50 = 114...
June 23, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28639409/anti-pd-1-antibodies-in-metastatic-uveal-melanoma-a-treatment-option
#6
Carolin Bender, Alexander Enk, Ralf Gutzmer, Jessica C Hassel
Uveal melanomas (UMs) are a rare form of cancer with clinical and pathological characteristics distinct from cutaneous melanomas. Ipilimumab has shown efficacy and safety in the treatment of metastatic UM. This provides a rationale for treatment with other immune checkpoint inhibitors. This is a retrospective review of 15 patients with metastatic UM treated between June 2014 and February 2016, who received treatment with the anti-PD-1 Abs pembrolizumab or nivolumab. Patients were treated at two German university hospitals...
June 21, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28638795/potential-prognostic-biomarkers-in-pancreatic-juice-of-resectable-pancreatic-ductal-adenocarcinoma
#7
REVIEW
Shefali Agrawal
Despite potentially curative surgery pancreatic cancer has a dismal prognosis. Serum cancer antigen 19-9 (CA 19-9) correlates with tumor burden, resectability and survival in patients with pancreatic ductal adenocarcinoma. Identification of novel biomarkers may facilitate early diagnosis of pancreatic cancer and improve survival. Pancreatic juice is a rich source of cancer-specific proteins rendering it a promising tool for identifying biomarkers. Recent proteomic and microRNA expression analyses have identified several biomarkers of potential diagnostic and prognostic value...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28630053/glucose-catabolism-in-liver-tumors-induced-by-c-myc-can-be-sustained-by-various-pkm1-pkm2-ratios-and-pyruvate-kinase-activities
#8
Andrés Méndez-Lucas, Xiaolei Li, Junjie Hu, Li Che, Xinhua Song, Jiaoyuan Jia, Jingxiao Wang, Chencheng Xie, Paul C Driscoll, Darjus F Tschaharganeh, Diego F Calvisi, Mariia Yuneva, Xin Chen
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL...
June 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28629818/corydalis-hendersonii-hemsl-protects-against-myocardial-injury-by-attenuating-inflammation-and-fibrosis-via-nf-%C3%AE%C2%BAb-and-jak2-stat3-signaling-pathways
#9
Ruifeng Bai, Xu Yin, Xiao Feng, Yuan Cao, Yan Wu, Zhixiang Zhu, Chun Li, Pengfei Tu, Xingyun Chai
ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis hendersonii Hemsl. (CH) with heat clearing and detoxifying effects are well described in Tibetan folk medicine. It has been used for centuries in China largely for the treatment of high altitude polycythemia, a pathophysiological condition referred to "plethora" in Tibetan medicine, hypertension, hepatitis, edema, gastritis, and other infectious diseases. AIM OF THE STUDY: To investigate the cardioprotective effects of Corydalis hendersonii extract in an ICR mouse model of myocardial ischemic injury...
June 16, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28624789/pediatric-and-adult-glioblastoma-radiosensitization-induced-by-pi3k-mtor-inhibition-causes-early-metabolic-alterations-detected-by-nuclear-magnetic-resonance-spectroscopy
#10
Alice Agliano, Geetha Balarajah, Daniela M Ciobota, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Martin O Leach, Nada M S Al-Saffar
Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. In this study, we show that NVP-BEZ235, a dual PI3K/mTOR inhibitor, potentiates the effects of irradiation in both adult and pediatric glioblastoma cell lines, resulting in early metabolic changes detected by nuclear magnetic resonance (NMR) spectroscopy. NVP-BEZ235 radiosensitises cells to X ray exposure, inducing cell death through the inhibition of CDC25A and the activation of p21cip1(CDKN1A)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624177/autophagy-can-alleviate-severe-burn-induced-damage-to-the-intestinal-tract-in-mice
#11
Duanyang Zhang, Wei Qiu, Peng Wang, Pan Zhang, Fang Zhang, PeiP Wang, Yong Sun
BACKGROUND: The present study was designed to examine the effect of autophagy and apoptosis on intestinal injury in mice after severe burns. METHODS: Kunming mice were subjected to third degree burns over 30% of the total body surface area. Damage to the intestine was assessed by examining changes in intestinal mucosal morphology, enzyme-linked immunosorbent assay of serum d-lactate, diamine oxidase, lipopolysaccharide, interleukin-6, and tumor necrosis factor α (marker of intestinal damage), hematoxylin and eosin staining, and Western blotting under 4 experimental conditions: control group, burn only (burn group), burn and administration of rapamycin to stimulate intestinal autophagy (rapamycin group), or burn and administration of 3-methyladenine to inhibit intestinal autophagy (3-methyladenine group)...
June 14, 2017: Surgery
https://www.readbyqxmd.com/read/28622713/mir-142-5p-promotes-development-of-colorectal-cancer-through-targeting-sdhb-and-facilitating-generation-of-aerobic-glycolysis
#12
Shaojun Liu, Zhiming Xiao, Feiyan Ai, Fen Liu, Xiong Chen, Ke Cao, Weiguo Ren, Xuemei Zhang, Peng Shu, Decai Zhang
Aberrant expression of miRNAs contributes to the development of human malignancies. A recent study revealed that miR-142-5p is increased in the serum of colorectal cancer (CRC) patients compared to health people. Using starBase v2.0, we found that succinate dehydrogenase-B (SDHB) is a potential target of miR-142-5p, while SDHB is negatively correlated to cancer development through regulating energetic metabolism. Based on these information, this study further examined the expression profiles of miR-142-5p and SDHB in CRC tissues and cell lines using PCR and Western blotting...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28620312/thermodynamics-in-gliomas-interactions-between-the-canonical-wnt-beta-catenin-pathway-and-ppar-gamma
#13
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28619042/metabolic-targeting-of-hif-dependent-glycolysis-reduces-lactate-increases-oxygen-consumption-and-enhances-response-to-high-dose-single-fraction-radiotherapy-in-hypoxic-solid-tumors
#14
Eric Leung, Rob A Cairns, Naz Chaudary, Ravi N Vellanki, Tuula Kalliomaki, Eduardo H Moriyama, Hilda Mujcic, Brian C Wilson, Bradly G Wouters, Richard Hill, Michael Milosevic
BACKGROUND: A high rate of glycolysis leading to elevated lactate content has been linked to poor clinical outcomes in patients with head and neck and cervical cancer treated with radiotherapy. Although the biological explanation for this relationship between lactate and treatment response remains unclear, there is a continued interest in evaluating strategies of targeting metabolism to enhance the effectiveness of radiotherapy. The goal of this study was to investigate the effect of metabolic-targeting through HIF-1α inhibition and the associated changes in glycolysis, oxygen consumption and response on the efficacy of high-dose single-fraction radiotherapy (HD-SFRT)...
June 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28611673/reversing-egfr-mediated-immunoescape-by-targeted-monoclonal-antibody-therapy
#15
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Uncontrolled growth is a signature of carcinogenesis, in part mediated by overexpression or overstimulation of growth factor receptors. The epidermal growth factor receptor (EGFR) mediates activation of multiple oncogenic signaling pathways and escape from recognition by the host immune system. We discuss how EGFR signaling downregulates tumor antigen presentation, upregulates suppressive checkpoint receptor ligand programmed death ligand (PD-L1), induces secretion of inhibitory molecules such as transforming growth factor beta (TGFβ) and reprograms the metabolic pathways in cancer cells to upregulate aerobic glycolysis and lactate secretion that ultimately lead to impaired cellular immunity mediated by natural killer (NK) cell and cytotoxic T lymphocytes (CTL)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611296/does-the-1h-nmr-plasma-metabolome-reflect-the-host-tumor-interactions-in-human-breast-cancer
#16
Vincent Richard, Raphaël Conotte, David Mayne, Jean-Marie Colet
Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide. There is an obvious need for a better understanding of BC biology. Alterations in the serum metabolome of BC patients have been identified but their clinical significance remains elusive. We evaluated by 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy, filtered plasma metabolome of 50 early (EBC) and 15 metastatic BC (MBC) patients. Using Principal Component Analysis, Partial Least-Squares Discriminant Analysis and Hierarchical Clustering we show that plasma levels of glucose, lactate, pyruvate, alanine, leucine, isoleucine, glutamate, glutamine, valine, lysine, glycine, threonine, tyrosine, phenylalanine, acetate, acetoacetate, β-hydroxy-butyrate, urea, creatine and creatinine are modulated across patients clusters...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28610954/feedback-regulation-of-aldoa-activates-the-hif-1%C3%AE-mmp9-axis-to-promote-lung-cancer-progression
#17
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yi Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28609750/association-of-plasma-cd40l-with-acute-chest-syndrome-in-sickle-cell-anemia
#18
Vanessa Tonin Garrido, Laura Sonzogni, Siana Nkya Mtatiro, Fernando F Costa, Nicola Conran, Swee Lay Thein
Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We sought to evaluate the association of CD40L and inflammation with sickle-related clinical complications and laboratory variables in SCA patients. Soluble CD40L, thrombospondin (TSP)-1 and tumor necrosis factor (TNF)-α were determined in the platelet-poor plasma of healthy individuals and steady-state SCA patients by ELISA...
June 10, 2017: Cytokine
https://www.readbyqxmd.com/read/28604752/tumor-cell-derived-lactate-induces-taz-dependent-upregulation-of-pd-l1-through-gpr81-in-human-lung-cancer-cells
#19
J Feng, H Yang, Y Zhang, H Wei, Z Zhu, B Zhu, M Yang, W Cao, L Wang, Z Wu
The clinical success of immunotherapy that inhibits the negative immune regulatory pathway programmed cell death protein 1/PD-1 ligand (PD-1/PD-L1) has initiated a new era in the treatment of metastatic cancer. PD-L1 expression is upregulated in many solid tumors including lung cancer and functions predominantly in lactate-enriched tumor microenvironments. Here, we provided evidence for PD-L1 induction in response to lactate stimulation in lung cancer cells. Lactate-induced PD-L1 induction was mediated by its receptor GPR81...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28604662/upregulation-of-mitochondrial-nad-levels-impairs-the-clonogenicity-of-ssea1-glioblastoma-tumor-initiating-cells
#20
Myung Jin Son, Jae-Sung Ryu, Jae Yun Kim, Youjeong Kwon, Kyung-Sook Chung, Seon Ju Mun, Yee Sook Cho
Emerging evidence has emphasized the importance of cancer therapies targeting an abnormal metabolic state of tumor-initiating cells (TICs) in which they retain stem cell-like phenotypes and nicotinamide adenine dinucleotide (NAD(+)) metabolism. However, the functional role of NAD(+) metabolism in regulating the characteristics of TICs is not known. In this study, we provide evidence that the mitochondrial NAD(+) levels affect the characteristics of glioma-driven SSEA1(+) TICs, including clonogenic growth potential...
June 9, 2017: Experimental & Molecular Medicine
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