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oncologic metabolic emergencies

Camila L P Oliveira, Stephanie Mattingly, Ralf Schirrmacher, Michael B Sawyer, Eugene J Fine, Carla M Prado
The predominant use of glucose anaerobically by cancer cells (Warburg effect) may be the most important characteristic the majority of these cells have in common and, therefore, a potential metabolic pathway to be targeted during cancer treatment. Because this effect relates to fuel oxidation, dietary manipulation has been hypothesized as an important strategy during cancer treatment. As such, the concept of a ketogenic diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism) rather than a dietary approach...
March 30, 2017: Journal of the Academy of Nutrition and Dietetics
Michael D Nyquist, Bhagwat Prasad, Elahe A Mostaghel
Solute Carrier (SLC) transporters are a large superfamily of transmembrane carriers involved in the regulated transport of metabolites, nutrients, ions and drugs across cellular membranes. A subset of these solute carriers play a significant role in the cellular uptake of many cancer therapeutics, ranging from chemotherapeutics such as antimetabolites, topoisomerase inhibitors, platinum-based drugs and taxanes to targeted therapies such as tyrosine kinase inhibitors. SLC transporters are co-expressed in groups and patterns across normal tissues, suggesting they may comprise a coordinated regulatory circuit serving to mediate normal tissue functions...
March 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Elisa Orioli, Elena De Marchi, Anna Lisa Giuliani, Elena Adinolfi
P2X7 receptor is an ion channel activated by extracellular adenosine trisphosphate (eATP) that attracted increasing attention for its role in immune reactions, neurobiology and oncology. As receptor for an extracellular ligand, P2X7 activates a series of intracellular signalling pathways mainly via alterations of the ion permeability, but also through formation of a large unselective pore and direct interaction with other proteins. Here we wish to give an overview on the main biochemical paths initiated by P2X7 activation by revising recent and established literature on P2X7-triggered signalling cascades leading to cell death, inflammatory and immune response activation, proliferation and metabolism modulation...
March 3, 2017: Current Medicinal Chemistry
Balazs Balint, Csaba Weber, Francisco Cruzalegui, Mike Burbridge, Andras Kotschy
DYRK1A is an emerging biological target with implications in diverse therapeutic areas such as neurological disorders (Down syndrome in particular), metabolism, and oncology. Harmine, a natural product that selectively inhibits DYRK1A amongst kinases could serve as a tool compound to better understand the biological processes that arise from DYRK1A inhibition. On the other hand harmine is also a potent inhibitor of monoamine oxidase A (MAO-A). Using structure-based design we have synthesized a collection of harmine analogs with tunable selectivity towards these two enzymes...
March 6, 2017: ChemMedChem
M Gacci, G I Russo, C De Nunzio, A Sebastianelli, M Salvi, L Vignozzi, A Tubaro, G Morgia, S Serni
BACKGROUND: Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features. METHODS: A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4-5 according to the novel prostate cancer grading system)...
February 21, 2017: Prostate Cancer and Prostatic Diseases
Suzanne Ackloo, Peter J Brown, Susanne Müller
Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about 4 thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro...
January 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Alessandra Fierabracci, Marsha Pellegrino
p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development...
November 25, 2016: International Journal of Molecular Sciences
N V Maluchenko, H W Chang, M T Kozinova, M E Valieva, N S Gerasimova, A V Kitashov, M P Kirpichnikov, P G Georgiev, V M Studitsky
Conventional antitumor therapy is often complicated by the emergence of the so-called cancer stem cells (CSCs), which are characterized by low metabolic rates and high resistance to almost all existing therapies. Many problems of clinical oncology and a poor efficacy of current treatments in particular are ascribed to CSCs. Therefore, it is important to develop new compounds capable of eliminating both rapidly proliferating tumor cells and standard treatment-resistant CSCs. Curaxins have been demonstrated to manifest various types of antitumor activity...
July 2016: Molekuliarnaia Biologiia
Onofrio Antonio Catalano, William Roger Masch, Ciprian Catana, Umar Mahmood, Dushyant Vasudeo Sahani, Michael Stanley Gee, Leon Menezes, Andrea Soricelli, Marco Salvatore, Debra Gervais, Bruce Robert Rosen
Hybrid PET/MR scanners are innovative imaging devices that simultaneously or sequentially acquire and fuse anatomical and functional data from magnetic resonance (MR) with metabolic information from positron emission tomography (PET) (Delso et al. in J Nucl Med 52:1914-1922, 2011; Zaidi et al. in Phys Med Biol 56:3091-3106, 2011). Hybrid PET/MR scanners have the potential to greatly impact not only on medical research but also, and more importantly, on patient management. Although their clinical applications are still under investigation, the increased worldwide availability of PET/MR scanners, and the growing published literature are important determinants in their rising utilization for primarily clinical applications...
September 13, 2016: Abdominal Radiology
J C Faivre, J F Py, G Vogin, G Martinage, J Salleron, P Royer, N Grandgirard, D Pasquier, S Thureau
Analgesic external beam radiation therapy is a standard of care for patients with uncomplicated painful bone metastases and/or prevention of bone complications. In case of fracture risk, radiation therapy is performed after surgery in a consolidation of an analgesic purpose and stabilizing osteosynthesis. Radiotherapy is mandatory after vertebroplasty or kyphoplasty. Spinal cord compression - the only emergency in radiation therapy - is indicated postoperatively either exclusively for non surgical indication...
October 2016: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
Giulio Nicita, Alberto Martini, Maria T Filocamo, Calogero Saieva, Aldo Tosto, Niceta Stomaci, Barbara Bigazzi, Donata Villari
OBJECTIVES: To present our experience with a sigmoid orthotopic neobladder. METHODS: We retrospectively evaluated the functional and oncological outcomes of 160 patients who underwent orthotopic neobladder reconstruction using a detubularized 20-25-cm sigmoid segment at our institution. Each patient was evaluated every 3 months the first year, every 6 months for the next 4 years and annually thereafter. Urodynamic studies of all consenting patients were carried out after 6 months, and 2, 5 and 10 years...
December 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Ivayla Apostolova, Florian Wedel, Winfried Brenner
Molecular imaging employing PET/CT enables in vivo visualization, characterization, and measurement of biologic processes in tumors at a molecular and cellular level. Using specific metabolic tracers, information about the integrated function of multiple transporters and enzymes involved in tumor metabolic pathways can be depicted, and the tracers can be directly applied as biomarkers of tumor biology. In this review, we discuss the role of F-18-fluorodeoxyglucose (FDG) as an in vivo glycolytic marker which reflects alterations of glucose metabolism in cancer cells...
2016: Recent Results in Cancer Research
Andrea Viale, Giulio F Draetta
A major barrier to achieving durable remission and a definitive cure in oncology patients is the emergence of tumor resistance, a common outcome of different disease types, and independent from the therapeutic approach undertaken. In recent years, subpopulations of slow-cycling cells endowed with enhanced tumorigenic potential and multidrug resistance have been isolated in different tumors, and mounting experimental evidence suggests these resistant cells are responsible for tumor relapse. An in-depth metabolic characterization of resistant tumor stem cells revealed that they rely more on mitochondrial respiration and less on glycolysis than other tumor cells, a finding that challenges the assumption that tumors have a primarily glycolytic metabolism and defective mitochondria...
2016: Recent Results in Cancer Research
J Arredondo, J Baixauli, C Pastor, A Chopitea, J J Sola, I González, J A-Cienfuegos, P Martínez, J Rodriguez, J L Hernández-Lizoain
PURPOSE: Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. METHODS AND PATIENTS: Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed...
March 2017: Clinical & Translational Oncology
Giulia Ottaviani, Valentina Martinelli, Katia Rupel, Nicoletta Caronni, Asma Naseem, Lorenzo Zandonà, Giuseppe Perinetti, Margherita Gobbo, Roberto Di Lenarda, Rossana Bussani, Federica Benvenuti, Mauro Giacca, Matteo Biasotto, Serena Zacchigna
Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression...
September 2016: EBioMedicine
Hannah Lennon, Matthew Sperrin, Ellena Badrick, Andrew G Renehan
There is a common perception that excess adiposity, commonly approximated by body mass index (BMI), is associated with reduced cancer survival. A number of studies have emerged challenging this by demonstrating that overweight and early obese states are associated with improved survival. This finding is termed the "obesity paradox" and is well recognized in the cardio-metabolic literature but less so in oncology. Here, we summarize the epidemiological findings related to the obesity paradox in cancer. Our review highlights that many observations of the obesity paradox in cancer reflect methodological mechanisms including the crudeness of BMI as an obesity measure, confounding, detection bias, reverse causality, and a specific form of the selection bias, known as collider bias...
September 2016: Current Oncology Reports
Gongda Xue, Emanuela Romano, Daniela Massi, Mario Mandalà
WNT signaling regulates embryonic development and tissue homeostasis in the adult stage. Evolutionarily, activation of the WNT pathway is triggered by a large family of cytokines and activates a broad spectrum of downstream targets through two independent branches mediated by β-catenin (defined as canonical pathway) or PLC and small GTPase (defined as non-canonical pathway), respectively. Recent studies revealed the crucial role of WNT in the maintenance of cell metabolism and stemness as well as its deregulation in tumourigenesis and malignant transformation through oncogenic reprogramming, which contributes to cancer cell proliferation and differentiation, survival, stress response and resistance...
September 2016: Cancer Treatment Reviews
Roberta Peruzzo, Lucia Biasutto, Ildikò Szabò, Luigi Leanza
Cancer research is nowadays focused on the identification of possible new targets in order to try to develop new drugs for curing untreatable tumors. Ion channels have emerged as "oncogenic" proteins, since they have an aberrant expression in cancers compared to normal tissues and contribute to several hallmarks of cancer, such as metabolic re-programming, limitless proliferative potential, apoptosis-resistance, stimulation of neo-angiogenesis as well as cell migration and invasiveness. In recent years, not only the plasma membrane but also intracellular channels and transporters have arisen as oncological targets and were proposed to be associated with tumorigenesis...
October 2016: European Biophysics Journal: EBJ
Ju Hye Jeong, Ihn Ho Cho, Kyung Ah Chun, Eun Jung Kong, Sang Don Kwon, Jae Hwang Kim
PURPOSE: Fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI) share the same role in clinical oncology and it is feasible to obtain the standardized uptake value (SUV) and apparent diffusion coefficient (ADC) simultaneously by emerging the hybrid positron emission tomography/magnetic resonance (PET/MR). This study investigated the correlation between the ADCs of rectal cancer lesions and their SUVs derived from hybrid PET/MR...
June 2016: Nuclear Medicine and Molecular Imaging
Pınar Özgen Kiratli, Murat Tuncel, Zvi Bar-Sever
Nuclear medicine has an important role in the management of many cancers in pediatric age group with multiple imaging modalities and radiopharmaceuticals targeting various biological uptake mechanisms. 18-Flourodeoxyglucose is the radiotracer of choice especially in patients with sarcoma and lymphoma. (18)FDG-PET, for sarcoma and lymphomas, is proved to be superior to conventional imaging in staging and therapy response. Although studies are limited in pediatric population, (18)FDG-PET/CT has found its way through international guidelines...
July 2016: Seminars in Nuclear Medicine
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