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Metabolically Supported Chemotherapy

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https://read.qxmd.com/read/30809285/msc-delivered-soluble-trail-and-paclitaxel-as-novel-combinatory-treatment-for-pancreatic-adenocarcinoma
#1
Filippo Rossignoli, Carlotta Spano, Giulia Grisendi, Elisabetta Manuela Foppiani, Giulia Golinelli, Ilenia Mastrolia, Marco Bestagno, Olivia Candini, Tiziana Petrachi, Alessandra Recchia, Francesca Miselli, Giulia Rovesti, Giulia Orsi, Elena Veronesi, Gregorio Medici, Benedetta Petocchi, Massimo Pinelli, Edwin M Horwitz, Pierfranco Conte, Massimo Dominici
Pancreatic cancer is the fourth leading cause of cancer death in western countries with more than 100,000 new cases per year in Europe and a mortality rate higher than 90%. In this scenario, advanced therapies based on gene therapies are emerging, thanks to a better understanding of tumour architecture and cancer cell alterations. We have demonstrated the efficacy of an innovative approach for pancreatic cancer based on mesenchymal stromal cells (MSC) genetically engineered to produce TNF-related Apoptosis Inducing Ligand (TRAIL)...
2019: Theranostics
https://read.qxmd.com/read/30791936/amp-activated-protein-kinase-a-potential-therapeutic-target-for-triple-negative-breast-cancer
#2
REVIEW
Wei Cao, Jieqing Li, Qiongyu Hao, Jaydutt V Vadgama, Yong Wu
Triple-negative breast cancer (TNBC) is an aggressive subset of breast carcinomas that lack expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Unlike other breast cancer subtypes, targeted therapy is presently unavailable for patients with TNBC. In spite of initial responses to chemotherapy, drug resistance tends to develop rapidly and the prognosis of metastatic TNBC is poor. Hence, there is an urgent need for novel-targeted treatment methods or development of safe and effective alternatives with recognized mechanism(s) of action...
February 21, 2019: Breast Cancer Research: BCR
https://read.qxmd.com/read/30781938/baseline-pet-as-prognostic-index-in-diffuse-large-b-cell-lymphoma-and-grade-iiib-follicular-lymphoma-a-retrospective-study-of-a-single-centre-experience
#3
Leonardo Campiotti, Diego De Palma, Luigina Guasti, Ilaria Proserpio, Sabrina Casagrande, Ilaria Schiorlin, Elena Bolzacchini, Matteo Suter, Francesca Ogliari, Alessandro Squizzato
BACKGROUND: International guidelines support performing baseline positron emission tomography (PET) in lymphoma. Metabolic tumor volume (MTV) measurement has been proposed as a good measurement of disease burden. We investigated if MTV at baseline PET can be predictive of complete response (CR) to first line standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) and in follicular lymphoma (FL) grade 3b. METHODS: We retrospectively analyzed data on54 consecutive patients with DLBCL and FL grade 3b treated in our institution...
February 14, 2019: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/30715556/role-of-bone-marrow-adipocytes-in-leukemia-and-chemotherapy-challenges
#4
REVIEW
Azin Samimi, Majid Ghanavat, Saeid Shahrabi, Shirin Azizidoost, Najmaldin Saki
Adipose tissue (AT) is an extramedullary reservoir of normal hematopoietic stem cells (HSCs). Adipocytes prevent the production of normal HSCs via secretion of inflammatory factors, and adipocyte-derived free fatty acids may contribute to the development and progression of leukemia via providing energy for leukemic cells. In addition, adipocytes are able to metabolize and inactivate therapeutic agents, reducing the concentrations of active drugs in adipocyte-rich microenvironments. The aim of this study was to detect the role of adipocytes in the progression and treatment of leukemia...
February 4, 2019: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/30710323/pretreatment-metabolic-tumour-volume-in-stage-iiia-b-non-small-cell-lung-cancer-uncovers-differences-in-effectiveness-of-definitive-radiochemotherapy-schedules-analysis-of-the-espatue-randomized-phase-3-trial
#5
Maja Guberina, Wilfried Eberhardt, Martin Stuschke, Thomas Gauler, Clemens Aigner, Martin Schuler, Georgios Stamatis, Dirk Theegarten, Walter Jentzen, Ken Herrmann, Christoph Pöttgen
PURPOSE: According to the ACRIN 6668/RTOG 0235 trial, pretreatment metabolic tumour volume (MTV) as detected by 18 F-fluorodeoxyglucose PET/CT is a prognostic factor in patients with stage III non-small-cell lung cancer (NSCLC) after definitive radiochemotherapy (RCT). To validate the prognostic value of MTV in patients with stage III NSCLC after RCT, we analysed mature survival data from the German phase III trial ESPATUE. METHODS: This analysis included patients who were staged by PET/CT and who were enrolled in the ESPATUE trial, a randomized study comparing definitive RCT (arm A) with surgery (arm B) after induction chemotherapy and RCT in patients with resectable stage IIIA/IIIB NSCLC...
February 1, 2019: European Journal of Nuclear Medicine and Molecular Imaging
https://read.qxmd.com/read/30661649/metabolic-syndrome-as-cardiovascular-risk-factor-in-childhood-cancer-survivors
#6
REVIEW
V G Pluimakers, M van Waas, S J C M M Neggers, M M van den Heuvel-Eibrink
Over the past decades, survival rates of childhood cancer have increased considerably from 5 to 30% in the early seventies to current rates exceeding 80%. This is due to the development of effective chemotherapy, surgery, radiotherapy and stem cell transplantation, combined with an optimized stratification of therapy and better supportive care regimens. As a consequence, active surveillance strategies of late sequelae have been developed to improve the quality of survival. Several epidemiological studies have reported an increased incidence of (components of) metabolic syndrome (MetS) and cardiovascular disease in childhood cancer survivors (CCS)...
January 2019: Critical Reviews in Oncology/hematology
https://read.qxmd.com/read/30624982/altered-skeletal-muscle-microtubule-mitochondrial-vdac2-binding-is-related-to-bioenergetic-impairments-after-paclitaxel-but-not-vinblastine-chemotherapies
#7
Sofhia V Ramos, Meghan C Hughes, Christopher G R Perry
Microtubule-targeting chemotherapies are linked to impaired cellular metabolism which may contribute to skeletal muscle dysfunction. However, the mechanisms by which metabolic homeostasis is perturbed remains unknown. Tubulin, the fundamental unit of microtubules, has been implicated in the regulation of mitochondrial-cytosolic ADP/ATP exchange through its interaction with the outer membrane voltage-dependent anion channel (VDAC). Based on this model, we predicted that disrupting microtubule architecture with the stabilizer paclitaxel and destabilizer vinblastine would impair skeletal muscle mitochondrial bioenergetics...
January 9, 2019: American Journal of Physiology. Cell Physiology
https://read.qxmd.com/read/30580268/a-randomised-controlled-trial-to-assess-whether-prehabilitation-improves-fitness-in-patients-undergoing-neoadjuvant-treatment-prior-to-oesophagogastric-cancer-surgery-study-protocol
#8
Sophie Allen, Vanessa Brown, Pradeep Prabhu, Michael Scott, Timothy Rockall, Shaun Preston, Javed Sultan
INTRODUCTION: Neoadjuvant therapy prior to oesophagogastric resection is the gold standard of care for patients with T2 and/or nodal disease. Despite this, studies have taught us that chemotherapy decreases patients' functional capacity as assessed by cardiopulmonary exercise (CPX) testing. We aim to show that a multimodal prehabilitation programme, comprising supervised exercise, psychological coaching and nutritional support, will physically, psychologically and metabolically optimise these patients prior to oesophagogastric cancer surgery so they may better withstand the immense physical and metabolic stress placed on them by radical curative major surgery...
December 22, 2018: BMJ Open
https://read.qxmd.com/read/30578254/mechanisms-of-immune-escape-after-allogeneic-hematopoietic-cell-transplantation
#9
Robert Zeiser, Luca Vago
Relapse of the original disease is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT) for acute leukemias. There is growing evidence that relapses may be explained not only by resistance to chemotherapy but also by the escape of tumor cells from the control of the allogeneic immune response. Mechanisms of immune evasion can involve abrogation of leukemia cell recognition due to the loss of HLA genes, immunosuppression by immune checkpoint ligand expression, production of anti-inflammatory factors, release of metabolically active enzymes, loss of pro-inflammatory cytokine production and acquisition of novel driver mutations that promote leukemia outgrowth...
December 21, 2018: Blood
https://read.qxmd.com/read/30573182/manipulation-of-glucose-and-hydroperoxide-metabolism-to-improve-radiation-response
#10
REVIEW
John M Floberg, Julie K Schwarz
Dysregulated glucose and redox metabolism are near universal features of cancers. They therefore represent potential selectively toxic metabolic targets. This review outlines the preclinical and clinical data for targeting glucose and hydroperoxide metabolism in cancer, with a focus on drug strategies that have the most available evidence. In particular, inhibition of glycolysis using 2-deoxyglucose, and inhibition of redox metabolism using the glutathione pathway inhibitor buthionine sulfoximine and the thioredoxin pathway inhibitor auranofin, have shown promise in preclinical studies to increase sensitivity to chemotherapy and radiation by increasing intracellular oxidative stress...
January 2019: Seminars in Radiation Oncology
https://read.qxmd.com/read/30573180/exercise-as-adjunct-therapy-in-cancer
#11
REVIEW
Kathleen A Ashcraft, Allison Betof Warner, Lee W Jones, Mark W Dewhirst
Data from observational studies indicate that both physical activity as well as exercise (ie, structured physical activity) is associated with reductions in the risk of recurrence and cancer mortality after a diagnosis of certain forms of cancer. Emerging evidence from preclinical studies indicates that physical activity/exercise paradigms regulate intratumoral vascular maturity and perfusion, hypoxia, and metabolism and augments the antitumor immune response. Such responses may, in turn, enhance response to standard anticancer treatments...
January 2019: Seminars in Radiation Oncology
https://read.qxmd.com/read/30564555/notch-signaling-regulates-mitochondrial-metabolism-and-nf-%C3%AE%C2%BAb-activity-in-triple-negative-breast-cancer-cells-via-ikk%C3%AE-dependent-non-canonical-pathways
#12
Fokhrul Hossain, Claudia Sorrentino, Deniz A Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M Minter, Todd E Golde, Barbara A Osborne, Lucio Miele
Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown...
2018: Frontiers in Oncology
https://read.qxmd.com/read/30450049/combined-metabolic-targeting-with-metformin-and-the-nsaids-diflunisal-and-diclofenac-induces-apoptosis-in-acute-myeloid-leukemia-cells
#13
Kathrin Renner, Anton Seilbeck, Nathalie Kauer, Ines Ugele, Peter J Siska, Christina Brummer, Christina Bruss, Sonja-Maria Decking, Matthias Fante, Astrid Schmidt, Kathrin Hammon, Katrin Singer, Sebastian Klobuch, Simone Thomas, Eva Gottfried, Katrin Peter, Marina Kreutz
The accelerated metabolism of tumor cells, inevitable for maintaining high proliferation rates, is an emerging target for tumor therapy. Increased glucose and lipid metabolism as well as mitochondrial activity have been shown in solid tumors but also in leukemic cells. As tumor cells are able to escape the blockade of one metabolic pathway by a compensatory increase in other pathways, treatment strategies simultaneously targeting metabolism at different sites are currently developed. However, the number of clinically applicable anti-metabolic drugs is still limited...
2018: Frontiers in Pharmacology
https://read.qxmd.com/read/30443293/chemical-modulation-of-autophagy-as-an-adjunct-to-chemotherapy-in-childhood-and-adolescent-brain-tumors
#14
REVIEW
Juliette Servante, Jasper Estranero, Lisethe Meijer, Rob Layfield, Richard Grundy
Brain tumors are the leading cause of cancer-related death in children and are the most challenging childhood cancer in relation to diagnosis, treatment, and outcome. One potential novel strategy to improve outcomes in cancer involves the manipulation of autophagy, a fundamental process in all cells. In cancer, autophagy can be thought of as having a "Janus"-like duality. On one face, especially in the early phases of cancer formation, autophagy can act as a cellular housekeeper to eliminate damaged organelles and recycle macromolecules, thus acting as tumor suppressor...
October 16, 2018: Oncotarget
https://read.qxmd.com/read/30426593/pyruvate-secreted-from-patient-derived-cancer-associated-fibroblasts-supports-survival-of-primary-lymphoma-cells
#15
Akihiko Sakamoto, Shunsuke Kunou, Kazuyuki Shimada, Makoto Tsunoda, Tomohiro Aoki, Chisako Iriyama, Akihiro Tomita, Shigeo Nakamura, Fumihiko Hayakawa, Hitoshi Kiyoi
Cancer-associated fibroblasts (CAFs) are a key component in the tumor microenvironment and play functional roles in tumor metastasis and resistance to chemotherapies. We have previously reported that CAFs isolated from lymphoma samples increase anaerobic glycolysis and decrease intracellular production of reactive oxygen species, promoting the survival of tumor cells. Here, we analyzed the mechanisms underlying this support of tumor-cell survival by CAFs. As direct contact between lymphoma cells and CAFs was not indispensable to survival support, we identified that the humoral factor pyruvate was significantly secreted by CAFs...
November 13, 2018: Cancer Science
https://read.qxmd.com/read/30412271/complementary-pharmacokinetic-profiles-of-netupitant-and-palonosetron-support-the-rationale-for-their-oral-fixed-combination-for-the-prevention-of-chemotherapy-induced-nausea-and-vomiting
#16
James Gilmore, Alberto Bernareggi
NEPA is the first fixed-combination antiemetic composed of the neurokinin-1 receptor antagonist netupitant (netupitant; 300 mg) and the 5-hydroxytryptamine-3 receptor antagonist palonosetron (palonosetron; 0.50 mg). This study evaluated the pharmacokinetic profiles of netupitant and palonosetron. The pharmacokinetic profiles of both drugs were summarized using data from phase 1-3 clinical trials. netupitant and palonosetron have high absolute bioavailability (63%-87% and 97%, respectively). Their overall systemic exposures and maximum plasma concentrations are similar under fed and fasting conditions...
November 9, 2018: Journal of Clinical Pharmacology
https://read.qxmd.com/read/30263060/pre-pro-and-synbiotics-in-cancer-prevention-and-treatment-a-review-of-basic-and-clinical-research
#17
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://read.qxmd.com/read/30244973/pml-regulated-mitochondrial-metabolism-enhances-chemosensitivity-in-human-ovarian-cancers
#18
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://read.qxmd.com/read/30231327/addressing-the-unintentional-consequences-of-cancer-therapy-with-novel-integrative-therapeutics
#19
REVIEW
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://read.qxmd.com/read/30229902/pyruvate-dehydrogenase-kinase-1-contributes-to-cisplatin-resistance-of-ovarian-cancer-through-egfr-activation
#20
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
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