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https://www.readbyqxmd.com/read/28724258/lldt-288-a-novel-triptolide-analogue-exhibits-potent-antitumor-activity-in-vitro-and-in-vivo
#1
Hongtao Xu, Xiaoting Fan, Guanjun Zhang, Xiaoyu Liu, Zhihong Li, Yuanchao Li, Biao Jiang
(14S)-14β-(1-(2-morpholinoethyl)-1H-indazol-5-ylamino)mthylepitriptolide (LLDT-288) was a novel C14β-heterocycle aminomethyl substituent triptolide analogue, which showed comparable cytotoxicity to triptolide. Here we demonstrated that LLDT-288 displayed broad-spectrum, potent antitumor activity, effectively against drug-resistance cancer cells, and induced apoptosis in vitro, but exerted low toxicity. Moreover, it exhibited a remarkable microsomal stability, and showed no inhibitory effects on different cytochrome P450 isoforms...
July 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28723673/energy-metabolism-in-glioblastoma-stem-cells-ppar%C3%AE-a-metabolic-adaptor-to-intratumoral-microenvironment
#2
Alessia Fidoamore, Loredana Cristiano, Chiara Laezza, Renato Galzio, Elisabetta Benedetti, Benedetta Cinque, Andrea Antonosante, Michele d'Angelo, Vanessa Castelli, Maria Grazia Cifone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini
Glioblastoma (GB), the most-common cancer in the adult brain, despite surgery and radio/ chemotherapy, is to date almost incurable. Many hypoxic tumors, including GB, show metabolic reprogramming to sustain uncontrolled proliferation, hypoxic conditions and angiogenesis. Peroxisome Proliferator-activated Receptors (PPAR), particularly the α isotype, have been involved in the control of energetic metabolism. Herein, we characterized patient-derived GB neurospheres focusing on their energetic metabolism and PPARα expression...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723644/fir-haplodeficiency-promotes-splicing-to-pyruvate-kinase-m2-in-mice-thymic-lymphoma-tissues-revealed-by-six-plex-tandem-mass-tag-quantitative-proteomic-analysis
#3
Asako Kimura, Kouichi Kitamura, Guzhanuer Ailiken, Mamoru Satoh, Toshinari Minamoto, Nobuko Tanaka, Fumio Nomura, Kazuyuki Matsushita
The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723573/proteomic-and-metabolomic-characterization-of-a-mammalian-cellular-transition-from-quiescence-to-proliferation
#4
Ho-Joon Lee, Mark P Jedrychowski, Arunachalam Vinayagam, Ning Wu, Ng Shyh-Chang, Yanhui Hu, Chua Min-Wen, Jodene K Moore, John M Asara, Costas A Lyssiotis, Norbert Perrimon, Steven P Gygi, Lewis C Cantley, Marc W Kirschner
There exist similarities and differences in metabolism and physiology between normal proliferative cells and tumor cells. Once a cell enters the cell cycle, metabolic machinery is engaged to facilitate various processes. The kinetics and regulation of these metabolic changes have not been properly evaluated. To correlate the orchestration of these processes with the cell cycle, we analyzed the transition from quiescence to proliferation of a non-malignant murine pro-B lymphocyte cell line in response to IL-3...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723563/a-positive-feedback-loop-between-sestrin2-and-mtorc2-is-required-for-the-survival-of-glutamine-depleted-lung-cancer-cells
#5
Jun-Kyu Byun, Yeon-Kyung Choi, Ji-Hyun Kim, Ji Yun Jeong, Hui-Jeon Jeon, Mi-Kyung Kim, Ilseon Hwang, Shin-Yup Lee, You Mie Lee, In-Kyu Lee, Keun-Gyu Park
Proper regulation of mTORC1 and mTORC2 upon nutrient starvation is critical for cancer cell survival. Upregulation of Sestrin2 in response to glutamine deprivation rescues cell death by suppressing mTORC1. However, the contribution of mTORC2 to Sestrin2-mediated mTORC1 suppression remains unclear. Here, we report that both Sestrin2 and mTORC2 are upregulated in glutamine-depleted lung cancer cells. Moreover, glutamine depletion caused Sestrin2 to associate with mTORC2, which was required for the increase in Sestrin2 protein stability and the reduction in mTORC1 activity...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723517/practice-patterns-compared-with-evidence-based-strategies-for-the-management-of-androgen-deprivation-therapy-induced-side-effects-in-prostate-cancer-patients-results-of-a-european-web-based-survey
#6
Renée Bultijnck, Cristian Surcel, Guillaume Ploussard, Alberto Briganti, Pieter De Visschere, Jurgen Fütterer, Pirus Ghadjar, Gianluca Giannarini, Hendrik Isbarn, Christophe Massard, Prasanna Sooriakumaran, Massimo Valerio, Roderick van den Bergh, Piet Ost
BACKGROUND: Evidence-based recommendations are available for the management of androgen deprivation therapy (ADT)-induced side effects; however, there are no data on the implementation of the recommendations into daily practice patterns. OBJECTIVE: To compare practice patterns in the management of ADT-induced side effects with evidence-based strategies. DESIGN, SETTING, AND PARTICIPANTS: A European Web-based survey was conducted from January 16, 2015, to June 24, 2015...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#7
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28723125/pharmacokinetics-on-a-chip-using-label-free-sers-technique-for-programmable-dual-drug-analysis
#8
Jiayuan Fei, Lei Wu, Yizhi Zhang, Shenfei Zong, Zhuyuan Wang, Yiping Cui
Synergistic effects of dual or multiple drugs have attracted great attention in medical fields, especially in cancer therapies. We provide a programmable microfluidic platform for pharmacokinetic detection of multiple drugs in multiple cells. The well-designed microfluidic platform includes two 2 × 3 microarrays of cell chambers, two gradient generators, and several pneumatic valves. Through the combined use of valves and gradient generators, each chamber can be controlled to infuse different kinds of living cells and drugs with specific concentrations as needed...
June 23, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722707/nutrition-inflammation-and-cancer
#9
REVIEW
Laurence Zitvogel, Federico Pietrocola, Guido Kroemer
Quantitative and qualitative aspects of nutrition have a profound effect on leukocytes and thereby affect proinflammatory carcinogenic effects or anticancer immune responses. As a result, nutrition affects the incidence, natural progression and therapeutic response of malignant diseases, both in humans and in preclinical animal models. Here we discuss the molecular mechanisms through which alimentary cues modulate metabolic, microbial and neuroendocrine circuitries and thus affect the probability of developing premalignant lesions that progress to clinically manifested disease and the response to therapeutic intervention...
July 19, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28722495/sucrose-non-fermenting-related-kinase-expression-in-ovarian-cancer-and-correlation-with-clinical-features
#10
Elizabeth E Hopp, Stephanie M Cossette, Suresh N Kumar, Daniel Eastwood, Ramani Ramchandran, Erin Bishop
Sucrose non-fermenting related kinase (SNRK) is a serine/threonine kinase known to regulate cellular metabolism and adipocyte inflammation. Since alterations in adipocyte metabolism play a role in ovarian cancer metastasis, we investigated the expression of SNRK in benign and malignant human ovarian tissue using immunohistochemistry and qPCR. The number of SNRK positive (+) nuclei is increased in malignant tissue compared to benign tissue (21.03% versus 14.90%, p < .0431). The most strongly stained malignant SNRK+ nuclei were stage 1 compared to stage 2-4 disease...
July 19, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28722424/metabolic-study-of-cancer-cells-using-a-ph-sensitive-hydrogel-nanofiber-light-addressable-potentiometric-sensor
#11
Parmiss Mojir Shaibani, Hashem Etayash, Selvaraj Naicker, Kamaljit Kaur, Thomas Thundat
We report a simple, fast, and cost-effective approach that measures cancer cell metabolism and their response to anticancer drugs in real time. Using a Light Addressable Potentiometric Sensor integrated with pH sensitive hydrogel nanofibers (NF-LAPS), we detect localized changes in pH of the media as cancer cells consume glucose and release lactate. NF-LAPS shows a sensitivity response of 74 mV/pH for cancer cells. Cancer cells (MDA MB231) showed a response of ∼0.4 unit change in pH compared to virtually no change observed for normal cells (MCF10A)...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722313/cellular-glycosylation-senses-metabolic-changes-and-modulates-cell-plasticity-during-emt
#12
REVIEW
P Carvalho-Cruz, F Alisson-Silva, A R Todeschini, W B Dias
Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E-cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin and N-cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward Hexosamine Biosynthesis Pathway (HBP) which fuels aberrant glycosylation patterns that are extensively observed in cancer cells...
July 19, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28722177/metformin-induced-alterations-in-nucleotide-metabolism-cause-5-fluorouracil-resistance-but-gemcitabine-susceptibility-in-oesophageal-squamous-cell-carcinoma
#13
Charissa Mynhardt, Leonard Howard Damelin, Rupal Jivan, Jade Peres, Sharon Prince, Robin Bruce Veale, Demetra Mavri-Damelin
5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than 5-fold and 6-fold respectively, as assessed by MTT assay...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28721154/obesity-and-inflammation-the-linking-mechanism-and-the-complications
#14
Mohammed S Ellulu, Ismail Patimah, Huzwah Khaza'ai, Asmah Rahmat, Yehia Abed
Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28721126/the-thyroid-gland-in-postmenopausal-women-physiology-and-diseases
#15
REVIEW
Małgorzata Gietka-Czernel
The incidence of most thyroid diseases: hypothyroidism, nodular goitre, and cancer is highest among postmenopausal and elderly women. The diagnosis of thyroid dysfunction in this group of patients is difficult because the symptoms can be nonspecific or common with menopausal and ageing complaints. In the interpretation of thyroid function tests the physiological changes in secretion and metabolism of thyrotropin (TSH) and thyroid hormones must be considered, as well as the influence of comorbidities. Unrecognised thyroid dysfunction leads to increased: cardiovascular risk, bone fractures, cognitive impairment, depression, and mortality...
June 2017: Przeglad Menopauzalny, Menopause Review
https://www.readbyqxmd.com/read/28720669/muc1-mediated-metabolic-alterations-regulate-response-to-radiotherapy-in-pancreatic-cancer
#16
Venugopal Gunda, Joshua J Souchek, Jaime Abrego, Surendra K Shukla, Gennifer D Goode, Enza Vernucci, Aneesha Dasgupta, Nina CHaika, Ryan J King, Sicong Li, Shuo Wang, Fang Yu, Tadayoshi Bessho, Chi Lin, Pankaj K Singh
Purpose: MUC1, an oncogene overexpressed in multiple solid tumors including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models. <p>Experimental design: We used MUC1 knockdown and overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response and metabolomic evaluations...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720668/efficient-mitochondrial-glutamine-targeting-prevails-over-glioblastoma-metabolic-plasticity
#17
Kristell Oizel, Cynthia Chauvin, Lisa Oliver, Catherine Gratas, Fanny Geraldo, Ulrich Jarry, Emmanuel Scotet, Marion Rabe, Marie-Clotilde Alves-Guerra, Raluca Teusan, Fabien Gautier, Delphine Loussouarn, Vincent Compan, Jean-Claude Martinou, François M Vallette, Claire Pecqueur
Purpose Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer, however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof-of concept for personalized metabolic targeting of GBM. <p> Experimental Design We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays and mitochondrial respirometry...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#18
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720593/vitamin-a-endocrine-tissues-and-hormones-interplay-and-interactions
#19
Julie Brossaud, Veronique Pallet, Jean-Benoit Corcuff
Vitamin A (retinol) is a micronutrient critical for cell proliferation and differentiation. In adults, vitamin A and metabolites such as retinoic acid (RA) play major roles in vision, immune and brain functions, and tissue remodelling and metabolism. This review presents the physiological interactions of retinoids and endocrine tissues and hormonal systems. Two endocrine systems have been particularly studied. In the pituitary, retinoids targets the corticotrophs with a possible therapeutic use in corticotropinomas...
July 18, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28720332/synthesis-and-biological-evaluation-of-fluoro-substituted-3-4-dihydroquinazoline-derivatives-for-cytotoxic-and-analgesic-effects
#20
Jin Han Kim, Hui Rak Jeong, Da Woon Jung, Hong Bin Yoon, Sun Young Kim, Hyoung Ja Kim, Kyung-Tae Lee, Vinicius M Gadotti, Junting Huang, Fang-Xiong Zhang, Gerald W Zamponi, Jae Yeol Lee
As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Cav3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound 8h (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Cav3.2 currents (>90% inhibition) at 10μM concentration and exhibited cytotoxic effect (IC50=5.9μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S...
July 8, 2017: Bioorganic & Medicinal Chemistry
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