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Cancer metabolism

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https://www.readbyqxmd.com/read/29668082/altered-stress-hormone-response-following-acute-exercise-during-prostate-cancer-treatment
#1
Erik D Hanson, Samy Sakkal, William S Evans, John A Violet, Claudio L Battaglini, Glenn K McConell, Alan Hayes
Exercise training reduces the side effects of cancer treatments, however, the stress hormone response to acute exercise during prostate cancer (PCa) treatment is unclear. PURPOSE: To examine the effects of acute exercise on circulating cortisol, epinephrine (Epi), and norepinephrine (NE) concentrations during PCa treatment with and without androgen deprivation therapy (ADT). METHODS: Men with PCa (n=11), with PCa on ADT (n=11) and non-cancer controls (n=8) had blood samples for stress hormones collected before and immediately (0h), 2h, and 24h after 45 minutes of intermittent cycling at 60% of peak wattage...
April 18, 2018: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/29667768/quinazoline-based-hydroxamic-acids-design-synthesis-and-evaluation-of-histone-deacetylase-inhibitory-effects-and-cytotoxicity
#2
Doan Thanh Hieu, Duong Tien Anh, Hai Pham-The, Le-Thi-Thu Huong, Eun Jae Park, Jeong Eun Choi, Jong Soon Kang, Sang-Bae Han, Phan Thi Phuong Dung, Nguyen-Hai Nam
In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a-i, 6a-i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g. 4g, 4c, 4g-i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat)...
April 18, 2018: Chemistry & Biodiversity
https://www.readbyqxmd.com/read/29667586/drug-drug-interactions-with-aprepitant-in-antiemetic-prophylaxis-for-chemotherapy
#3
R Schoffelen, A G Lankheet, C M L van Herpen, J J M van der Hoeven, I M E Desar, C Kramers
In the current guidelines to prevent hemotherapyinduced nausea and vomiting, multiple antiemetic drugs are administered simultaneously. In patients who receive highly emetogenic chemotherapy, aprepitant, an NK1-receptor antagonist, is combined with ondansetron and dexamethasone. Aprepitant can influence the pharmacokinetics of other drugs, as it is an inhibitor and inducer of CYP3A4. Some anticancer drugs and other co-medication frequently used in cancer patients are CYP3A4 or CYP29C substrates. We give an overview of the metabolism and current data on clinically relevant drug-drug interactions with aprepitant during chemotherapy...
April 2018: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/29667556/ultrasound-promoted-green-synthesis-docking-study-of-indole-spliced-thiadiazole-%C3%AE-amino-phosphonates-as-anticancer-agents-and-anti-tyrosinase-agents
#4
Anna Pratima G Nikalje, Pramod Gawhane, Shailee Tiwari, Jaiprakash Sangshetti, Manoj Damale
In this work, a new series of diethyl ((1H-indole-3-yl)((5-phenyl-1,3,4-thiadiazole-2- yl)amino)methyl)phosphonate derivatives 6(a-j) were designed and synthesized in Ultrasound by green protocol using Kabachnik-Fields reaction. The structures of the synthesized compounds were confirmed by spectral analysis such as elemental analyses, IR, 1H NMR, 13C NMR, 31P NMR and mass spectra. The synthesized compounds 6(a-j) were appraised for their in vitro anticancer activity against human cancer cell lines such as SK-MEL-2 (melanoma), IMR-32 (Neuroblastoma), HT-29(Colon) and also on normal murine embryonic fibroblast NIH/3T3 by Sulforhodamine B (SRB) assay, using Adriamycin as a standard drug...
April 17, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29667084/investigation-of-the-aryl-hydrocarbon-receptor-and-the-intrinsic-tumoral-component-of-the-kynurenine-pathway-of-tryptophan-metabolism-in-primary-brain-tumors
#5
Anthony R Guastella, Sharon K Michelhaugh, Neil V Klinger, Hassan A Fadel, Sam Kiousis, Rouba Ali-Fehmi, William J Kupsky, Csaba Juhász, Sandeep Mittal
INTRODUCTION: There is mounting evidence supporting the role of tryptophan metabolism via the kynurenine pathway (KP) in the pathogenesis of primary brain tumors. Under normal physiological conditions, the KP is the major catabolic pathway for the essential amino acid tryptophan. However, in cancer cells, the KP becomes dysregulated, depletes local tryptophan, and contributes to an immunosuppressive tumor microenvironment. METHODS: We examined the protein expression levels (in 73 gliomas and 48 meningiomas) of the KP rate-limiting enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and tryptophan 2,3-dioxygenase (TDO2), as well as, the aryl hydrocarbon receptor (AhR), a carcinogenic transcription factor activated by KP metabolites...
April 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29666895/suppression-of-glutathione-s-transferases-potentiates-the-cytotoxic-effect-of-phenethyl-isothiocyanate-in-cholangiocarcinoma-cells
#6
Ornanong Tusskorn, Tueanjai Khunluck, Auemduan Prawan, Laddawan Senggunprai, Upa Kukongviriyapan, Veerapol Kukongviriyapan
Phenethyl isothiocyanate (PEITC) is a potential cancer prevention agent that is found in cruciferous vegetables. Previous studies have shown that the effect of PEITC-induced cell death declines rapidly after administration. The metabolic fate of PEITC is modulated by glutathione S-transferases (GST). In this study, we investigated whether GST activity modulates PEITC-induced cytotoxicity on cholangiocarcinoma (CCA) cells. The sensitivity of KKU-M214 and KKU-100 cells to PEITC was associated with GST activity...
April 17, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29666838/a-brief-history-of-intracrine-androgen-metabolism-by-castration-recurrent-prostate-cancer
#7
REVIEW
James L Mohler
This mini-review describes the evolution of the concept of intracrine androgen metabolism by prostate cancer during androgen deprivation therapy. Persistence of androgen receptor protein in the face of castrate circulating levels of testosterone could not be explained fully by hypersensitization or mutation of the androgen receptor. The hypothesis that castration-recurrent prostate cancer produced its own testosterone was proven using radioimmunoassay and mass spectrometry methods adopted for use in prostate tissue...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29666732/renal-tubular-acidosis-an-adverse-effect-of-pd-1-inhibitor-immunotherapy
#8
Sandy El Bitar, Chanudi Weerasinghe, Elie El-Charabaty, Marcel Odaimi
Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29666465/molecular-epidemiology-of-lung-cancer-in-iran-implications-for-drug-development-and-cancer-prevention
#9
REVIEW
Zahra Fathi, Nicholas L Syn, Jian-Guo Zhou, Raheleh Roudi
Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017...
April 18, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29666172/genetic-editing-of-colonic-organoids-provides-a-molecularly-distinct-and-orthotopic-preclinical-model-of-serrated-carcinogenesis
#10
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
https://www.readbyqxmd.com/read/29665787/valproic-acid-sensitizes-metformin-resistant-human-renal-cell-carcinoma-cells-by-upregulating-h3-acetylation-and-emt-reversal
#11
Muyun Wei, Shaowei Mao, Guoliang Lu, Liang Li, Xiaopeng Lan, Zhongxian Huang, Yougen Chen, Miaoqing Zhao, Yueran Zhao, Qinghua Xia
BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear...
April 17, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29665526/novel-hydrazide-hydrazone-and-amide-substituted-coumarin-derivatives-synthesis-cytotoxicity-screening-microarray-radiolabeling-and-in-vivo-pharmacokinetic-studies
#12
Tamer Nasr, Samir Bondock, Hassan M Rashed, Walid Fayad, Mahmoud Youns, Tamer M Sakr
The current work presents the synthesis and biological evaluation of new series of coumarin hydrazide-hydrazone derivatives that showed in vitro broad spectrum antitumor activities against resistant pancreatic carcinoma (Panc-1), hepatocellular carcinoma (HepG2) and leukemia (CCRF) cell lines using doxorubicin as reference standard. Bromocoumarin hydrazide-hydrazone derivative (BCHHD) 11b showed excellent anticancer activity against all tested cancer cell lines. Enzyme assays showed that BCHHD 11b induced apoptosis due to activation of caspases 3/7...
April 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29665433/replication-protein-a-the-laxative-that-keeps-dna-regular-the-importance-of-rpa-phosphorylation-in-maintaining-genome-stability
#13
REVIEW
Brendan M Byrne, Gregory G Oakley
The eukaryotic ssDNA-binding protein, Replication protein A (RPA), was first discovered almost three decades ago. Since then, much progress has been made to elucidate the critical roles for RPA in DNA metabolic pathways that help promote genomic stability. The canonical RPA heterotrimer (RPA1-3) is an essential coordinator of DNA metabolism that interacts with ssDNA and numerous protein partners to coordinate its roles in DNA replication, repair, recombination and telomere maintenance. An alternative form of RPA, termed aRPA, is formed by a complex of RPA4 with RPA1 and RPA3...
April 14, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29665421/uhplc-q-tof-ms-ms-based-screening-and-identification-of-the-metabolites-in-vivo-after-oral-administration-of-betulin
#14
Wendan Zhang, Honghong Jiang, Miaomiao Jin, Qiao Wang, Qian Sun, Yingfeng Du, Liang Cao, Huijun Xu
Betulin is an active natural pentacyclic triterpene ingredient with valuable anti-cancer and anti-HIV efficacies. In the present study, an efficient approach was developed to screening and identification of metabolites and to assess the metabolic profiles of betulin in vivo using UHPLC-Q-TOF-MS/MS system based on multiple mass defect filter data acquisition (MMDF) and multiple data processing techniques. Based on the proposed method, 56 phase I and 6 phase II metabolites were detected in rats after oral administration of betulin...
April 14, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29665239/fbxw7-regulates-a-mitochondrial-transcription-program-by-modulating-mitf
#15
Franco Abbate, Brateil Badal, Karen Mendelson, Iraz Toprak Aydin, Madhavika N Serasinghe, Ramiz Iqbal, Jarvier Mohammed, Alexander Solovyov, Benjamin D Greenbaum, Jerry E Chipuk, Julide Tok Celebi
FBXW7 is well characterized as a tumor suppressor in many human cancers including melanoma; however, the mechanisms of tumor suppressive function have not been fully elucidated. We leveraged two distinct RNA sequencing datasets: human melanoma cell lines (n=10) with control versus silenced FBXW7 and a cohort of human melanoma tumor samples (n=51) in order to define the transcriptomic fingerprint regulated by FBXW7. Here, we report that loss of FBXW7 enhances a mitochondrial gene transcriptional program that is dependent on MITF in human melanoma and confers poor patient outcomes...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29665143/identification-of-potential-tumor-educated-platelets-rna-biomarkers-in-non-small-cell-lung-cancer-by-integrated-bioinformatical-analysis
#16
Linlin Xue, Li Xie, Xingguo Song, Xianrang Song
BACKGROUND: Platelets have emerged as key players in tumorigenesis and tumor progression. Tumor-educated platelet (TEP) RNA profile has the potential to diagnose non-small-cell lung cancer (NSCLC). The objective of this study was to identify potential TEP RNA biomarkers for the diagnosis of NSCLC and to explore the mechanisms in alternations of TEP RNA profile. METHODS: The RNA-seq datasets GSE68086 and GSE89843 were downloaded from Gene Expression Omnibus DataSets (GEO DataSets)...
April 17, 2018: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/29664675/knockout-of-glucose-transporter-glut6-has-minimal-effects-on-whole-body-metabolic-physiology-in-mice
#17
Frances L Byrne, Ellen M Olzomer, Robert Brink, Kyle L Hoehn
Glucose transporter 6 (GLUT6) is a member of the facilitative glucose transporter family. GLUT6 is up-regulated in several cancers, but is not widely expressed in normal tissues. Previous studies have shown that GLUT6 knockdown kills endometrial cancer cells that express elevated levels of the protein. However, whether GLUT6 represents a viable anti-cancer drug target is unclear because the role of GLUT6 in normal metabolic physiology is unknown. Herein we generated GLUT6 knockout mice to determine how loss of GLUT6 affected whole body glucose homeostasis and metabolic physiology...
April 17, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29664606/radiometal-dependent-biological-profile-of-the-radiolabeled-grpr-antagonist-sb3-in-cancer-theranostics-metabolic-and-biodistribution-patterns-defined-by-neprilysin
#18
Emmanouil Lymperis, Aikaterini Kaloudi, Werner Sallegger, Ingrid L Bakker, Eric P Krenning, Marion DeJong, Theodosia Maina, Berthold Artur Nock
Recent advances in oncology involve the use of diagnostic/therapeutic radionuclide-carrier pairs that target cancer cells, offering exciting opportunities for personalized patient treatment. Theranostic gastrin-releasing peptide receptor (GRPR)-directed radiopeptides have been proposed for the management of GRPR-expressing prostate and breast cancers. We have recently introduced the PET tracer 68Ga-SB3 (SB3, DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), a receptor-radioantagonist that enables the visualization of GRPR-positive lesions in human...
April 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29664569/fatty-acid-metabolism-in-cd8-t-cell-memory-challenging-current-concepts
#19
REVIEW
Brenda Raud, Peter J McGuire, Russell G Jones, Tim Sparwasser, Luciana Berod
CD8+ T cells are key members of the adaptive immune response against infections and cancer. As we discuss in this review, these cells can present diverse metabolic requirements, which have been intensely studied during the past few years. Our current understanding suggests that aerobic glycolysis is a hallmark of activated CD8+ T cells, while naive and memory (Tmem ) cells often rely on oxidative phosphorylation, and thus mitochondrial metabolism is a crucial determinant of CD8+ Tmem cell development. Moreover, it has been proposed that CD8+ Tmem cells have a specific requirement for the oxidation of long-chain fatty acids (LC-FAO), a process modulated in lymphocytes by the enzyme CPT1A...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29663896/molecular-interaction-and-computational-analytical-studies-of-pinocembrin-for-its-antiangiogenic-potential-targeting-vegfr-2-a-persuader-of-metastasis
#20
Neha Sharma, Mala Sharma, Eram Shakeel, Qazi M Sajid Jamal, Mohammad A Kamal, Usman Sayeed, Mohammad K A Khan, Mohammad H Siddiqui, Jamal M Arif, Salman Akhtar
BACKGROUND: Designing a novel antagonist against VEGFR-2 is being applied currently to inhibit cancer growth and metastasis. Because of the unexpected side effects incurred by the contemporary anticancer medications, the focus has been laid towards identifying natural compounds that might carry the potential to inhibit tumor progression. VEGR-2 remains an important target for anticancer drug development as it is the master regulator of vascular growth. OBJECTIVE: The study focuses on virtual screening of compounds from plants of Asteraceae family that bears antiangiogenic potential and thus, inhibiting VEGFR-2 using a computational approach...
April 16, 2018: Medicinal Chemistry
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