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https://www.readbyqxmd.com/read/28212276/preventive-effects-of-pentoxifylline-on-the-development-of-colonic-premalignant-lesions-in-obese-and-diabetic-mice
#1
Kazufumi Fukuta, Yohei Shirakami, Akinori Maruta, Koki Obara, Soichi Iritani, Nobuhiko Nakamura, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu
Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212191/endothelial-cell-metabolism-an-update-anno-2017
#2
Laure-Anne Teuwen, Nihed Draoui, Charlotte Dubois, Peter Carmeliet
PURPOSE OF REVIEW: Endothelial cell metabolism has recently emerged as an important coregulator of angiogenesis and is therefore a promising new target in various angiogenesis-associated illnesses, like cancer. In this review, we discuss recent insights in endothelial cell metabolism in both physiological and pathological conditions and discuss possible translational implications. RECENT FINDINGS: Two metabolic pathways that determine the performance of endothelial cells are glycolysis and fatty acid oxidation (FAO)...
February 15, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28212122/a-research-of-soft-tissue-lipoma-genesis-factor-with-immunohistochemical-analysis
#3
Jun Beom Lee, Hwan Jun Choi, Eun Taik Son, Jun Hyuk Kim
INTRODUCTION: Lipoma is the most familiar soft-tissue tumor. But the etiology of lipoma remains imprecise. Sex steroid hormones such as estrogen have effects on muscle and adipose tissue development. There is now significant evidence that sex steroids are involved in the site specificities of adipose tissue metabolism. This association of adipose tissue metabolism between sex steroid hormones suggests a possible role for sex steroids in the pathogenesis of lipoma. METHODS: To investigate this concept, the authors evaluated the expression of the estrogen receptor (ER) and the progesterone receptor (PR) in soft tissue lipoma in this study...
February 16, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28211980/constitutional-bone-impairment-in-noonan-syndrome
#4
Giuseppina Baldassarre, Alessandro Mussa, Diana Carli, Cristina Molinatto, Giovanni Battista Ferrero
Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211872/rictor-mtorc2-deficiency-enhances-keratinocyte-stress-tolerance-via-mitohormesis
#5
Beatrice Tassone, Stefania Saoncella, Francesco Neri, Ugo Ala, Davide Brusa, Mark A Magnuson, Paolo Provero, Salvatore Oliviero, Chiara Riganti, Enzo Calautti
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28211464/molecular-basis-of-abhd5-lipolysis-activation
#6
Matthew A Sanders, Huamei Zhang, Ljiljana Mladenovic, Yan Yuan Tseng, James G Granneman
Alpha-beta hydrolase domain-containing 5 (ABHD5), the defective gene in human Chanarin-Dorfman syndrome, is a highly conserved regulator of adipose triglyceride lipase (ATGL)-mediated lipolysis that plays important roles in metabolism, tumor progression, viral replication, and skin barrier formation. The structural determinants of ABHD5 lipolysis activation, however, are unknown. We performed comparative evolutionary analysis and structural modeling of ABHD5 and ABHD4, a functionally distinct paralog that diverged from ABHD5 ~500 million years ago, to identify determinants of ABHD5 lipolysis activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211215/zkscan1-gene-and-its-related-circular-rna-circzkscan1-both-inhibit-hepatocellular-carcinoma-cell-growth-migration-and-invasion-but-through-different-signaling-pathways
#7
Zhicheng Yao, Jingyan Luo, Kunpeng Hu, Jizong Lin, He Huang, Qiangliang Wang, Peng Zhang, Zhiyong Xiong, Zejian Huang, Chonghua He, Bo Liu, Yang Yang
There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development, but the regulation and function of human circRNAs remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circZKSCAN1 was significantly lower (P<0.05) in the HCC samples compared with that in matched adjacent non-tumorous tissues by reverse transcription PCR (RT-PCR)...
February 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28211128/staged-intraperitoneal-brachytherapy-and-hyperthermic-intraperitoneal-chemotherapy-in-an-adolescent-novel-anesthetic-challenges-for-pediatric-anesthetists
#8
Andrew D Weatherall, Tristan R Bennett, Mark Lovell, Winnie Fung, Jonathan de Lima
Newer techniques that have found a place in cancer management in adults are offered far less commonly in pediatric patients. We present a case of a patient with recurrent Wilms' tumor managed with a novel combination of cytoreductive surgery, intraperitoneal brachytherapy, and subsequent hyperthermic intraperitoneal chemotherapy. Each stage presents challenges that the pediatric anesthetist is unlikely to have faced before. Such cases require flexibility and thorough planning to manage the combination of major surgery, remote anesthesia with brachytherapy and hyperthermic chemotherapy with its potential for metabolic derangement, significant fluid shifts, analgesic care, and potential exposure of staff to cytotoxic agents...
February 17, 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28210996/quantitative-evaluation-of-oxygen-metabolism-in-the-intratumoral-hypoxia-18-f-fluoromisonidazole-and-15-o-labelled-gases-inhalation-pet
#9
Tadashi Watabe, Yasukazu Kanai, Hayato Ikeda, Genki Horitsugi, Keiko Matsunaga, Hiroki Kato, Kayako Isohashi, Kohji Abe, Eku Shimosegawa, Jun Hatazawa
BACKGROUND: Intratumoral hypoxia is one of the resistant factors in radiotherapy and chemotherapy for cancer. Although it is detected by (18)F-fluoromisonidazole (FMISO) PET, the relationship between intratumoral hypoxia and oxygen metabolism has not been studied. The purpose of this study was to evaluate the intratumoral perfusion and oxygen metabolism in hypoxic regions using the rat xenograft model. Ten male Fischer rats with C6 glioma (body weight = 220 ± 15 g) were investigated with (18)F-FMISO PET and steady-state inhalation method of (15)O-labelled gases PET...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28210259/resolution-of-cancer-promoting-inflammation-a-new-approach-for-anticancer-therapy
#10
REVIEW
Qi Zhang, Bo Zhu, Yongsheng Li
Inflammation is a protective response that eliminates harmful stimuli and restores tissue homeostasis, whereas the failure to resolve inflammation leads to the development of malignancies. Immune cells in the tumor inflammatory microenvironment endow cancer cells with their specific hallmarks, including mutations, metabolic reprograming, angiogenesis, invasion, and metastasis. Targeting the inflammatory microenvironment with anti-inflammatory drugs (e.g., aspirin) or by enhancing antitumor immunity (e.g., chimeric antigen receptor T cell therapy) has been extensively investigated and has achieved promising results in many cancers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28210221/pharmacogenomic-characterization-and-isobologram-analysis-of-the-combination-of-ascorbic-acid-and-curcumin-two-main-metabolites-of-curcuma-longa-in-cancer-cells
#11
Edna Ooko, Onat Kadioglu, Henry J Greten, Thomas Efferth
Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the Curcuma species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in C. longa. This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#12
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28209347/high-resolution-mass-spectrometry-based-method-applicable-for-a-wide-range-of-3-hydroxy-3-methyl-glutaryl-coenzyme-a-reductase-inhibitors-in-blood-serum-including-intermediates-and-products-of-the-cholesterol-biosynthetic-pathway
#13
Vít Kosek, Milena Stránská, Marie Fenclová, Tomáš Ruml, Libor Vítek, Jana Hajšlová
Statins belong to the major class of hypolipidemic drugs. They act as competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in the cholesterol biosynthetic pathway. This inhibition not only leads to the depletion of cholesterol and its fatty acid esters, but also to the depletion of the intermediates of this metabolic pathway (mainly pyrophosphates), which can play an important role in tumor proliferation. The aim of the current study was to establish a versatile multi-analyte method capable of quantitative determination of various currently-used statins, together with free cholesterol (FC), cholesterol esters (CEs), and some key intermediates of the mevalonate pathway occurring in human serum...
January 31, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28209178/tumor-initiating-cells-a-critical-review-of-isolation-approaches-and-new-challenges-in-targeting-strategies
#14
REVIEW
Komal Qureshi-Baig, Pit Ullmann, Serge Haan, Elisabeth Letellier
Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation and identification remain largely disputed and incompletely established. In this review, we discuss the latest developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC)...
February 16, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28208838/the-effect-of-metformin-and-gant61-combinations-on-the-radiosensitivity-of-prostate-cancer-cells
#15
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Ruth J Muschel, Karin Haustermans
The anti-diabetes drug metformin has been shown to have anti-neoplastic effects in several tumor models through its effects on energy metabolism and protein synthesis. Recent studies show that metformin also targets Hedgehog (Hh) signaling, a developmental pathway re-activated in several tumor types, including prostate cancer (PCa). Furthermore, we and others have shown that Hh signaling is an important target for radiosensitization. Here, we evaluated the combination of metformin and the Hh inhibitor GANT61 (GLI-ANTagonist 61) with or without ionizing radiation in three PCa cell lines (PC3, DU145, 22Rv1)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208747/multinucleated-giant-cancer-cells-produced-in-response-to-ionizing-radiation-retain-viability-and-replicate-their-genome
#16
Razmik Mirzayans, Bonnie Andrais, April Scott, Ying W Wang, Piyush Kumar, David Murray
Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21(WAF1) (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208646/recognition-of-local-dna-structures-by-p53-protein
#17
Václav Brázda, Jan Coufal
p53 plays critical roles in regulating cell cycle, apoptosis, senescence and metabolism and is commonly mutated in human cancer. These roles are achieved by interaction with other proteins, but particularly by interaction with DNA. As a transcription factor, p53 is well known to bind consensus target sequences in linear B-DNA. Recent findings indicate that p53 binds with higher affinity to target sequences that form cruciform DNA structure. Moreover, p53 binds very tightly to non-B DNA structures and local DNA structures are increasingly recognized to influence the activity of wild-type and mutant p53...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28206987/id2-promotes-survival-of-glioblastoma-cells-during-metabolic-stress-by-regulating-mitochondrial-function
#18
Zhonghua Zhang, Gilbert J Rahme, Pranam D Chatterjee, Matthew C Havrda, Mark A Israel
Tumor cells proliferate in cellular environments characterized by a lack of optimal tissue organization resulting oftentimes in compromised cellular metabolism affecting nutrition, respiration, and energetics. The response of tumor cells to adverse environmental conditions is a key feature affecting their pathogenicity. We found that inhibitor of DNA binding 2 (ID2) expression levels significantly correlate with the ability of glioblastoma (GBM)-derived cell lines to survive glucose deprivation. ID2 suppressed mitochondrial oxidative respiration and mitochondrial ATP production by regulating the function of mitochondrial electron transport chain (mETC) complexes, resulting in reduced superoxide and reactive oxygen species (ROS) production from mitochondria...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28206968/intratumoral-lactate-metabolism-in-barrett-s-esophagus-and-adenocarcinoma
#19
Heikki Huhta, Olli Helminen, Sami Palomäki, Joonas H Kauppila, Juha Saarnio, Petri P Lehenkari, Tuomo J Karttunen
BACKGROUND: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. RESULTS: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205616/dependence-on-glycolysis-sensitizes-braf-mutated-melanomas-for-increased-response-to-targeted-braf-inhibition
#20
Keisha N Hardeman, Chengwei Peng, Bishal B Paudel, Christian T Meyer, Thong Luong, Darren R Tyson, Jamey D Young, Vito Quaranta, Joshua P Fessel
Dysregulated metabolism can broadly affect therapy resistance by influencing compensatory signaling and expanding proliferation. Given many BRAF-mutated melanoma patients experience disease progression with targeted BRAF inhibitors, we hypothesized therapeutic response is related to tumor metabolic phenotype, and that altering tumor metabolism could change therapeutic outcome. We demonstrated the proliferative kinetics of BRAF-mutated melanoma cells treated with the BRAF inhibitor PLX4720 fall along a spectrum of sensitivity, providing a model system to study the interplay of metabolism and drug sensitivity...
February 16, 2017: Scientific Reports
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