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Metabolically Supported Chemotherapy

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https://www.readbyqxmd.com/read/30263060/pre-pro-and-synbiotics-in-cancer-prevention-and-treatment-a-review-of-basic-and-clinical-research
#1
REVIEW
Alasdair J Scott, Claire A Merrifield, Jessica A Younes, Elizabeth P Pekelharing
There is a growing appreciation of the role of the human microbiota in the pathophysiology of cancer. Pre-, pro- and synbiotics are some of the best evidenced means of manipulating the microbiota for therapeutic benefit and their potential role in the prevention and treatment of cancer has garnered significant interest. In this review, we discuss how these agents may have oncosuppressive effects by maintaining intestinal barrier function, immunomodulation, metabolism and preventing host cell proliferation. We highlight the epidemiological and trials-based evidence supporting a role for pre-, pro- and synbiotics in the prevention of cancer...
2018: Ecancermedicalscience
https://www.readbyqxmd.com/read/30244973/pml-regulated-mitochondrial-metabolism-enhances-chemosensitivity-in-human-ovarian-cancers
#2
Géraldine Gentric, Yann Kieffer, Virginie Mieulet, Oumou Goundiam, Claire Bonneau, Fariba Nemati, Ilse Hurbain, Graca Raposo, Tatiana Popova, Marc-Henri Stern, Valérie Lallemand-Breitenbach, Sebastian Müller, Tatiana Cañeque, Raphaël Rodriguez, Anne Vincent-Salomon, Hugues de Thé, Rodrigue Rossignol, Fatima Mechta-Grigoriou
High-grade serous ovarian cancer (HGSOC) remains an unmet medical challenge. Here, we unravel an unanticipated metabolic heterogeneity in HGSOC. By combining proteomic, metabolomic, and bioergenetic analyses, we identify two molecular subgroups, low- and high-OXPHOS. While low-OXPHOS exhibit a glycolytic metabolism, high-OXPHOS HGSOCs rely on oxidative phosphorylation, supported by glutamine and fatty acid oxidation, and show chronic oxidative stress. We identify an important role for the PML-PGC-1α axis in the metabolic features of high-OXPHOS HGSOC...
September 17, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/30231327/addressing-the-unintentional-consequences-of-cancer-therapy-with-novel-integrative-therapeutics
#3
Ting Bao, Luke J Peppone, Patricia Robinson
There are 15.5 million cancer survivors in the United States because of, in part, improvements in therapy. As a result, there will be an increased burden of long- and late-term complications of cancer care, such as metabolic alterations. These metabolic changes will include alterations in bone resorption, obesity, hypercholesterolemia, and diabetes mellitus. The majority of cancer treatment-related toxicities have focused on endocrine therapy; however, chemotherapy and supportive medications, such as steroids, contribute to the development of these disorders...
May 23, 2018: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/30229902/pyruvate-dehydrogenase-kinase-1-contributes-to-cisplatin-resistance-of-ovarian-cancer-through-egfr-activation
#4
Meng Zhang, Qing Cong, Xiao-Yan Zhang, Ming-Xing Zhang, Ying-Ying Lu, Cong-Jian Xu
Patients with ovarian cancer frequently develop acquired drug resistance after the long-term chemotherapy, leading to disease progression. Enhanced epithelial-mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian cancer cells; however, the molecular mechanisms involved are largely undefined. Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian cancer in terms of growth and EMT was investigated...
September 19, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30167086/inborn-like-errors-of-metabolism-are-determinants-of-breast-cancer-risk-clinical-response-and-survival-a-study-of-human-biochemical-individuality
#5
Ismael da Silva, Rene da Costa Vieira, Carolina Stella, Edson Loturco, André Lopes Carvalho, Carlos Veo, Cristovam Neto, Sandra M Silva, Paulo D'Amora, Marcia Salzgeber, Delcio Matos, Celso R Silva, Jose R Oliveira, Iara Rabelo, Patricia Yamakawa, Rui Maciel, Rosa Biscolla, Maria Chiamolera, Renato Fraietta, Felipe Reis, Marcelo Mori, Dirce Marchioni, Antonio Carioca, Gustavo Maciel, Renato Tomioka, Edmund Baracat, Clovis Silva, Celso Granato, Ricardo Diaz, Bruno Scarpellini, Daniel Egle, Heidi Fiegl, Irmgard Himmel, Christina Troi, Robert Nagourney
Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy...
August 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/30142422/n-3-polyunsaturated-fatty-acids-induce-acute-myeloid-leukemia-cell-death-associated-with-mitochondrial-glycolytic-switch-and-nrf2-pathway-activation
#6
Frédéric Picou, Christelle Debeissat, Jérôme Bourgeais, Nathalie Gallay, Elise Ferrié, Amélie Foucault, Noémie Ravalet, Aurore Maciejewski, Nicolas Vallet, Elfi Ducrocq, Lamya Haddaoui, Jorge Domenech, Olivier Hérault, Emmanuel Gyan
Acute Myeloid Leukemia (AML) remains a therapeutic challenge and improvements in chemotherapy are needed. n-3 polyunsaturated fatty acids (PUFAs), present in fish oil (FO) at high concentrations, have antitumoral properties in various cancer models. We investigated the effects of two n-3 PUFAs, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in AML cell lines and primary AML blasts. EPA and DHA induced a dose-dependent decrease in cell viability in five AML cell lines, which was also observed with FO, but not SO (devoid of n-3 PUFAs) in cell lines and primary leucoblasts...
August 22, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/30118981/structurally-graduated-collagen-scaffolds-applied-to-the-ex-vivo-generation-of-platelets-from-human-pluripotent-stem-cell-derived-megakaryocytes-enhancing-production-and-purity
#7
Jennifer H Shepherd, Daniel Howard, Amie K Waller, Holly Rebecca Foster, Annett Mueller, Thomas Moreau, Amanda L Evans, Meera Arumugam, Guénaëlle Bouët Chalon, Eleonora Vriend, Natalia Davidenko, Cedric Ghevaert, Serena M Best, Ruth E Cameron
Platelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells...
November 2018: Biomaterials
https://www.readbyqxmd.com/read/30115708/hypertension-and-severe-hypokalaemia-associated-with-ectopic-acth-production
#8
Tiago Lobo Ferreira, Tiago Nunes da Silva, Dolores Canário, Maria Francisca Delerue
Ectopic adrenocorticotropic hormone (ACTH) secretion represents 5%-10% of cases of Cushing's syndrome (CS), and approximately 50%-60% of these arise from neuroendocrine lung tumours, including small-cell lung cancer (SCLC). We report a 42-year-old man admitted with hypertension, metabolic alkalosis and severe hypokalaemia. On physical examination, centripetal obesity with 'moon face' and 'buffalo's hump' were identified, and wheezing on left lung was heard. A markedly elevated serum cortisol, ACTH and urine free cortisol production supported the diagnosis of CS...
August 16, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/30112440/double-blind-randomized-placebo-controlled-studies-evaluating-apaziquone-e09-qapzola%C3%A2-intravesical-instillation-post-transurethral-resection-of-bladder-tumors-for-the-treatment-of-low-risk-non-muscle-invasive-bladder-cancer
#9
Lawrence Karsh, Neal Shore, Mark Soloway, Gajanan Bhat, Guru Reddy, Szu-Yun Leu, J Alfred Witjes
Background: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. Objective: To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo. Methods: Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT...
July 30, 2018: Bladder Cancer
https://www.readbyqxmd.com/read/30079960/inherited-variation-in-the-xenobiotic-transporter-pathway-and-survival-of-multiple-myeloma-patients
#10
Angelica Macauda, Eleonora Castelli, Gabriele Buda, Matteo Pelosini, Aleksandra Butrym, Marzena Watek, Marcin Kruszewski, Annette Juul Vangsted, Marcin Rymko, Krzysztof Jamroziak, Niels Abildgaard, Eva Kannik Haastrup, Grzegorz Mazur, Rafael Ríos, Artur Jurczyszyn, Daria Zawirska, Marek Dudziński, Małgorzata Raźny, Magdalena Dutka, Waldemar Tomczak, Anna Suska, Agnieszka Druzd-Sitek, Herlander Marques, Mario Petrini, Miroslaw Markiewicz, Joaquin Martinez-Lopez, Lene Hyldahl Ebbesen, Elżbieta Iskierka-Jażdżewska, Juan Sainz, Federico Canzian, Daniele Campa
Over the past four decades, remarkable progress has been made in the treatment and prognosis of multiple myeloma (MM), although it remains an incurable disease. Chemotherapy resistance is a major hurdle for treatment efficacy. Drug resistance can be innate and so driven by genes involved in the drug metabolism pathways. We performed an association study of 71 germline variants within the major genes in those pathways (ABCB1, ABCC2, ABCG2, and their regulators NR1I2/PXR and NR1I3/CAR) in the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 1365 MM cases with survival information recruited in 5 European countries...
August 6, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29949843/sex-differences-in-cancer-epidemiology-genetics-and-therapy
#11
REVIEW
Hae-In Kim, Hyesol Lim, Aree Moon
The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women...
July 1, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29942509/beta-hydroxybutyrate-3-ohb-can-influence-the-energetic-phenotype-of-breast-cancer-cells-but-does-not-impact-their-proliferation-and-the-response-to-chemotherapy-or-radiation
#12
Catharina Bartmann, Sudha R Janaki Raman, Jessica Flöter, Almut Schulze, Katrin Bahlke, Jana Willingstorfer, Maria Strunz, Achim Wöckel, Rainer J Klement, Michaela Kapp, Cholpon S Djuzenova, Christoph Otto, Ulrike Kämmerer
Background: Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Therefore, we investigated the effect of a physiological concentration of 3 mM 3-OHB on metabolism, proliferation, and viability of breast cancer (BC) cells in vitro...
2018: Cancer & Metabolism
https://www.readbyqxmd.com/read/29913092/warburg-effect-lactate-dehydrogenase-and-radio-chemo-therapy-efficacy
#13
Michael I Koukourakis, Alexandra Giatromanolaki
The anaerobic metabolism of glucose by cancer cells, even under well-oxygenated conditions, has been documented by Otto Warburg as early as 1927. Micro-environmental hypoxia and intracellular pathways activating the hypoxia-related gene response, shift cancer cell metabolism to anaerobic pathways. In the current review, we focus on a major enzyme involved in anaerobic transformation of pyruvate to lactate, namely lactate dehydrogenase 5 (LDH5). The value of LDH5 as a marker of prognosis of cancer patients, as a predictor of response to radiotherapy (RT) and chemotherapy and, finally, as a major target for cancer treatment and radio-sensitization is reported and discussed...
October 16, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29899761/precision-diagnostics-of-ewing-s-sarcoma-by-liquid-biopsy-circulating-ews-fli1-fusion-transcripts
#14
Matteo Allegretti, Beatrice Casini, Chiara Mandoj, Stefania Benini, Laurent Alberti, Mariangela Novello, Elisa Melucci, Laura Conti, Renato Covello, Edoardo Pescarmona, Giuseppe Maria Milano, Alessio Annovazzi, Vincenzo Anelli, Virginia Ferraresi, Roberto Biagini, Patrizio Giacomini
Background: Limited information is available on the applicative value of liquid biopsy (LB) in rare tumors, including Ewing's sarcoma (ES). The accepted precision diagnostics standards would greatly benefit from a non-invasive LB test monitoring pathognomonic gene rearrangements in the bloodstream. Methods: Tissue and blood samples were collected from six and four ES patients, respectively. Plasma was cleared by two successive rounds of centrifugation and stored frozen until RNA extraction by the QIAmp CNA kit...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29888201/the-mitochondrial-citrate-carrier-slc25a1-sustains-redox-homeostasis-and-mitochondrial-metabolism-supporting-radioresistance-of-cancer-cells-with-tolerance-to-cycling-severe-hypoxia
#15
Julian Hlouschek, Christine Hansel, Verena Jendrossek, Johann Matschke
Pronounced resistance of lung cancer cells to radiotherapy and chemotherapy is a major barrier to successful treatment. Herein, both tumor hypoxia and the upregulation of the cellular antioxidant defense systems observed during malignant progression can contribute to radioresistance. We recently found that exposure to chronic cycling severe hypoxia/reoxygenation stress results in glutamine-dependent upregulation of cellular glutathione (GSH) levels and associated radiation resistance opening novel routes for tumor cell-specific radiosensitization...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29845757/pathway-analysis-of-genetic-variants-in-folate-mediated-one-carbon-metabolism-related-genes-and-survival-in-a-prospectively-followed-cohort-of-colorectal-cancer-patients
#16
Jennifer Ose, Akke Botma, Yesilda Balavarca, Katharina Buck, Dominique Scherer, Nina Habermann, Jolantha Beyerle, Katrin Pfütze, Petra Seibold, Elisabeth J Kap, Axel Benner, Lina Jansen, Katja Butterbach, Michael Hoffmeister, Hermann Brenner, Alexis Ulrich, Martin Schneider, Jenny Chang-Claude, Barbara Burwinkel, Cornelia M Ulrich
Folate-mediated one-carbon metabolism (FOCM) is a key pathway essential for nucleotide synthesis, DNA methylation, and repair. This pathway is a critical target for 5-fluorouracil (5-FU), which is predominantly used for colorectal cancer (CRC) treatment. A comprehensive assessment of polymorphisms in FOCM-related genes and their association with prognosis has not yet been performed. Within 1,739 CRC cases aged ≥30 years diagnosed from 2003 to 2007 (DACHS study), we investigated 397 single nucleotide polymorphisms (SNPs) and 50 candidates in 48 FOCM-related genes for associations with overall- (OS) and disease-free survival (DFS) using multiple Cox regression (adjusted for age, sex, stage, grade, BMI, and alcohol)...
May 29, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29788890/inhibition-of-pyruvate-dehydrogenase-kinase-as-a-therapeutic-strategy-against-cancer
#17
REVIEW
Swatishree Sradhanjali, Mamatha M Reddy
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate Dehydrogenase Kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it...
2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29764892/intense-exercise-for-survival-among-men-with-metastatic-castrate-resistant-prostate-cancer-interval-gap4-a-multicentre-randomised-controlled-phase-iii-study-protocol
#18
Robert U Newton, Stacey A Kenfield, Nicolas H Hart, June M Chan, Kerry S Courneya, James Catto, Stephen P Finn, Rosemary Greenwood, Daniel C Hughes, Lorelei Mucci, Stephen R Plymate, Stephan F E Praet, Emer M Guinan, Erin L Van Blarigan, Orla Casey, Mark Buzza, Sam Gledhill, Li Zhang, Daniel A Galvão, Charles J Ryan, Fred Saad
INTRODUCTION: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS AND ANALYSIS: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC)...
May 14, 2018: BMJ Open
https://www.readbyqxmd.com/read/29764822/numb-chin-syndrome-an-ominous-sign-of-mandibular-metastasis
#19
Abdul Razak, Bee See Goh, Jothi Raamahlingam Rajaran, Abd Jabar Nazimi
A 51-year-old woman a known case of stage 2 breast carcinoma in 2006 and underwent left mastectomy performed in the same year presented with bilateral lower limb pain suggestive of spinal pathology, and left chin numbness, both of 2 weeks' duration. Examination revealed left mandibular hypoesthesia without any other sign or symptoms. Orthopantomogram was unremarkable apart from mild alveolar bone expansion at tooth 36 area, which was extracted 3 months earlier. Subsequently, a full-body positron emission tomography contrast enhanced computer tomography revealed hypermetabolic lesions of her axial (excluding skull) and appendicular skeleton...
May 14, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29759441/nuclear-organization-mediates-cancer-compromised-genetic-and-epigenetic-control
#20
REVIEW
Sayyed K Zaidi, Andrew J Fritz, Kirsten M Tracy, Jonathan A Gordon, Coralee E Tye, Joseph Boyd, Andre J Van Wijnen, Jeffrey A Nickerson, Antony N Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2...
August 2018: Advances in Biological Regulation
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