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Cancer metabolism

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https://www.readbyqxmd.com/read/29458144/disruption-of-peroxisome-function-leads-to-metabolic-stress-mtor-inhibition-and-lethality-in-liver-cancer-cells
#1
Mengjiao Cai, Xiao Sun, Wenchao Wang, Zhusheng Lian, Ping Wu, Suxia Han, Huan Chen, Pumin Zhang
Peroxisome houses a large number of enzymes involved in lipid and phytochemical oxidation as well as synthesis of bile acid and other specialized lipids. Peroxisome resident enzymes are imported into the organelle via a conserved cargo transport system composed of many peroxins, protein factors essential for the biogenesis of peroxisome. Among the peroxins, PEX5 plays a transporter role, and PEX2, 10, and 12 are thought to form a complex that functions as an E3 ubiquitin ligase to help recycle PEX5 in an ubiquitin modification-dependent process...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458109/modulation-of-cyp1a1-metabolism-from-adverse-health-effects-to-chemoprevention-and-therapeutic-options
#2
Melina Mescher, Thomas Haarmann-Stemmann
The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29457831/low-t3-syndrome-as-a-predictor-of-poor-prognosis-in-chronic-lymphocytic-leukemia
#3
Rui Gao, Rui-Ze Chen, Yi Xia, Jin-Hua Liang, Li Wang, Hua-Yuan Zhu, Jia-Zhu Wu, Lei Fan, Jian-Yong Li, Tao Yang, Wei Xu
Low triiodothyronine (T3) state is associated with poor prognosis in critical acute and prolonged illness. However, the information on thyroid dysfunction and cancer is limited. The aim of our study was to evaluate the prognostic value of low T3 syndrome in chronic lymphocytic leukemia (CLL). Two hundred and fifty-eight patients with detailed thyroid hormone profile at CLL diagnosis were enrolled. Low T3 syndrome was defined by low free T3 (FT3) level accompanied by normal-to-low free tetraiodothyronine (FT4) and thyroid-stimulating hormone (TSH) levels...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29457496/prostate-cancer-risk-reduced-by-physical-activity-even-among-men-with-prolonged-sitting-time-a-study-from-vietnam
#4
Dong Van Hoang, Andy H Lee, Ngoc Minh Pham, Colin W Binns
Increasing prostate cancer incidence in the Asia-Pacific region may be related to a more sedentary lifestyle resulted from economic growth and rapid urbanization. The present case-control study of 640 men aged 64 to 75 years was conducted in Vietnam between 2013 and 2015 to ascertain the relationship between physical activity and prostate cancer risk, accounting for the duration of sitting time. Reduced prostate cancer risks were found for men engaging in medium (15.8-47.3 metabolic equivalent task [MET]-h/week) and high (>47...
February 1, 2018: Asia-Pacific Journal of Public Health
https://www.readbyqxmd.com/read/29456846/l-carnitine-supplementation-reduces-the-general-fatigue-of-cancer-patients-during-chemotherapy
#5
Hiroki Matsui, Takahiro Einama, Shunsuke Shichi, Ryo Kanazawa, Kazuaki Shibuya, Takashi Suzuki, Fumihiko Matsuzawa, Taku Hashimoto, Shigenori Homma, Junji Yamamoto, Akinobu Taketomi, Hironori Abe
L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC deficiency is associated with a feeling of weakness or general fatigue. Cancer patients receiving chemotherapy often develop LC deficiency, which is considered to be a factor contributing to general fatigue. The aim of the present study was to evaluate the efficacy of LC supplementation as a treatment for general fatigue in cancer patients during chemotherapy. A total of 11 cancer patients who were suffering from general fatigue during chemotherapy in our hospital between September 2014 and December 2015 were examined (6 cases involved adjuvant chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent disease)...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29456767/biochemical-characterization-of-two-clinically-relevant-human-fumarase-variants-defective-for-oligomerization
#6
REVIEW
Artemisa Bulku, Todd M Weaver, Melanie B Berkmen
Background: Fumarase, a significant enzyme of energy metabolism, catalyzes the reversible hydration of fumarate to L-malate. Mutations in the FH gene, encoding human fumarase, are associated with fumarate hydratase deficiency (FHD) and hereditary leiomyomatosis and renal cell cancer (HLRCC). Fumarase assembles into a homotetramer, with four active sites. Interestingly, residues from three of the four subunits within the homotetramer comprise each active site. Hence, any mutation affecting oligomerization is predicted to disrupt enzyme activity...
2018: Open Biochemistry Journal
https://www.readbyqxmd.com/read/29456764/integrative-analysis-of-the-epigenetic-basis-of-muscle-invasive-urothelial-carcinoma
#7
Thomas Sanford, Maxwell V Meng, Reema Railkar, Piyush K Agarwal, Sima P Porten
Background: Elucidation of epigenetic alterations in bladder cancer will lead to further understanding of the biology of the disease and hopefully improved therapies. Our aim was to perform an integrative epigenetic analysis of invasive urothelial carcinoma of the bladder to identify the epigenetic abnormalities involved in the development and progression of this cancer. Methods: Pre-processed methylation data and RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and processed using the R package TCGA-Assembler...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29455665/pten-ptenp1-regulating-the-regulator-of-rtk-dependent-pi3k-akt-signalling-new-targets-for-cancer-therapy
#8
REVIEW
Nahal Haddadi, Yiguang Lin, Glena Travis, Ann M Simpson, Eileen M McGowan, Najah T Nassif
Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455660/the-relevance-of-tyrosine-kinase-inhibitors-for-global-metabolic-pathways-in-cancer
#9
REVIEW
Michaela Poliaková, Daniel M Aebersold, Yitzhak Zimmer, Michaela Medová
Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyrosine kinases (TKs) involved in proliferation, metastasis and growth count for several years to promising anti-cancer approaches. In this respect, small molecule inhibitors are the most widely used clinically relevant means for targeted therapy, with a rising number of approvals for TKs inhibitors...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455648/mechanisms-of-receptor-tyrosine-kinase-activation-in-cancer
#10
REVIEW
Zhenfang Du, Christine M Lovly
Receptor tyrosine kinases (RTKs) play an important role in a variety of cellular processes including growth, motility, differentiation, and metabolism. As such, dysregulation of RTK signaling leads to an assortment of human diseases, most notably, cancers. Recent large-scale genomic studies have revealed the presence of various alterations in the genes encoding RTKs such as EGFR, HER2/ErbB2, and MET, amongst many others. Abnormal RTK activation in human cancers is mediated by four principal mechanisms: gain-of-function mutations, genomic amplification, chromosomal rearrangements, and / or autocrine activation...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455645/pyruvate-kinase-m2-fuels-multiple-aspects-of-cancer-cells-from-cellular-metabolism-transcriptional-regulation-to-extracellular-signaling
#11
REVIEW
Ming-Chuan Hsu, Wen-Chun Hung
Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455637/molecular-dynamics-of-interaction-of-sesamin-and-related-compounds-with-the-cancer-marker-%C3%AE-catenin-an-in-silico-study
#12
Bindu Madhuri Cavuturu, Vishwambar Vishnu Bhandare, Amutha Ramaswamy, Neelakantan Arumugam
By virtue of their regulatory role in the biological process, certain protein-protein complexes form potential targets for designing and discovery of drugs. Alteration set in the controlled formation of such complexes results in dysregulation of several metabolic processes, leading to diseased condition. β-catenin/Tcf4 complex is one such protein-protein complex found altered in colorectal epithelial cells resulting in activation of target genes leading to cancer. Recently certain lignans from seeds of the oil crop sesame were found inhibiting initiation and progression of this type of cancer...
February 18, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29455338/extracellular-atp-is-differentially-metabolized-on-papillary-thyroid-carcinoma-cells-surface-in-comparison-to-normal-cells
#13
Ana Paula Santin Bertoni, Rafael Paschoal de Campos, Marisa Tsao, Elizandra Braganhol, Tania Weber Furlanetto, Márcia Rosângela Wink
The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells...
February 17, 2018: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/29454887/metabolomic-analysis-uncovered-an-association-of-serum-phospholipid-levels-with-estrogen-induced-mammary-tumors-in-female-aci-seg-rats
#14
Yoshinori Okamoto, Akira Aoki, Koji Ueda, Hideto Jinno
Estrogen is reported to be involved in mammary tumorigenesis. To unveil metabolic signatures for estrogen-induced mammary tumorigenesis, we carried out serum metabolomic analysis in an estrogen-induced mammary tumor model, female August Copenhagen-Irish/Segaloff (ACI/Seg) rats, using liquid chromatography-mass spectrometry. In contrast to the control group, all rats with an implanted 17β-estradiol (E2) pellet developed mammary tumors during this experiment. E2 treatment significantly suppressed body weight gain...
February 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29454647/dynamic-plasticity-of-macrophage-functions-in-diseased-liver
#15
Thomas Ritz, Oliver Krenkel, Frank Tacke
Liver macrophages attract increasing interest due to their crucial roles in homeostasis and hepatic diseases. Recent findings in mice and man suggest a remarkable phenotypic and functional diversity of liver macrophages. Kupffer cells, the subset of tissue resident macrophages with sentinel functions in liver, mainly arise from embryogenic precursors, whereas in injury, liver tissue is engrafted by monocyte-derived macrophages. Both principal macrophage populations respond to local or systemic signals and have substantial effects on reduction as well as aggravation of hepatic diseases...
December 20, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29454575/targeting-complement-mediated-immunoregulation-for-cancer-immunotherapy
#16
REVIEW
Martin Kolev, Maciej M Markiewski
Complement was initially discovered as an assembly of plasma proteins "complementing" the cytolytic activity of antibodies. However, our current knowledge places this complex system of several plasma proteins, receptors, and regulators in the center of innate immunity as a bridge between the initial innate responses and adaptive immune reactions. Consequently, complement appears to be pivotal for elimination of pathogens, not only as an early response defense, but by directing the subsequent adaptive immune response...
February 14, 2018: Seminars in Immunology
https://www.readbyqxmd.com/read/29454261/frequency-of-somatic-tp53-mutations-in-combination-with-known-pathogenic-mutations-in-colon-adenocarcinoma-non-small-cell-lung-carcinoma-and-gliomas-as-identified-by-next-generation-sequencing
#17
Zahra Shajani-Yi, Francine B de Abreu, Jason D Peterson, Gregory J Tsongalis
The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective...
February 13, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29453983/aldolase-a-overexpression-is-associated-with-poor-prognosis-and-promotes-tumor-progression-by-the-epithelial-mesenchymal-transition-in-colon-cancer
#18
Feng Ye, Yixing Chen, Lu Xia, Jiabian Lian, Shuyu Yang
There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453779/mitochondrial-cytochrome-p450-cyp-1b1-is-responsible-for-melatonin-induced-apoptosis-in-neural-cancer-cells
#19
Zhenlong Yu, Xiangge Tian, Yuling Peng, Zheng Sun, Chao Wang, Ning Tang, Bin Li, Yuqing Jian, Wei Wang, Xiaokui Huo, Xiaochi Ma
Melatonin is an endogenous indoleamine with a wide range of biological functions in the various organisms from bacteria to mammals. Evidence indicates that melatonin facilitates apoptosis in cancer cells and enhances the anti-tumor activity of chemotherapy in animals and clinical studies. However, the melatonin metabolism and the key metabolic targets in cancer cells still remain unknown. In this study, U118 and SH-SY5Y tumor cell lines were used to investigate the metabolic pathways of melatonin in cancer cells...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29453600/argininosuccinate-synthetase-1-ass1-loss-in-high-grade-neuroendocrine-carcinomas-of-the-urinary-bladder-implications-for-targeted-therapy-with-adi-peg-20
#20
Sounak Gupta, Divya Sahu, John S Bomalaski, Igor Frank, Stephen A Boorjian, Prabin Thapa, John C Cheville, Donna E Hansel
High-grade neuroendocrine carcinomas (HGNECs) of the urinary bladder encompass small cell (SCNEC) and large cell neuroendocrine carcinomas (LCNEC). Currently, recommended initial management is with systemic chemotherapy, followed by consolidative therapy with either radical cystectomy or radiotherapy in patients with localized disease. Nevertheless, survival in this setting remains poor. We therefore evaluated the potential to modify arginine metabolism as an alternative, targeted therapy approach in these carcinomas...
February 16, 2018: Endocrine Pathology
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