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https://www.readbyqxmd.com/read/29348889/metformin-and-temozolomide-a-synergic-option-to-overcome-resistance-in-glioblastoma-multiforme-models
#1
Silvia Valtorta, Alessia Lo Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29344202/metformin-in-combination-with-cisplatin-inhibits-cell-viability-and-induces-apoptosis-of-human-ovarian-cancer-cells-by-inactivating-erk-1-2
#2
Jian-Hong Dang, Zhi-Jun Jin, Xiao-Jun Liu, Dian Hu, Jing Wang, Yan Luo, Ling-Ling Li
Metformin protects against insulin resistance by restoring insulin sensitivity and may also possess anticancer activity. The aim of the present study was to investigate the effects of metformin alone or combined with cisplatin (DDP) on the cell viability and apoptosis of HO-8910 human ovarian cancer cells, and to investigate metformin as a potential novel therapeutic for treating ovarian cancer. The viability of HO-8910 cells was assessed using a cell proliferation and cytotoxicity assay following treatment with different concentrations of metformin (0...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343628/keeping-the-home-fires-burning-amp-activated-protein-kinase
#3
REVIEW
D Grahame Hardie
Living cells obtain energy either by oxidizing reduced compounds of organic or mineral origin or by absorbing light. Whichever energy source is used, some of the energy released is conserved by converting adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which are analogous to the chemicals in a rechargeable battery. The energy released by the conversion of ATP back to ADP is used to drive most energy-requiring processes, including cell growth, cell division, communication and movement. It is clearly essential to life that the production and consumption of ATP are always maintained in balance, and the AMP-activated protein kinase (AMPK) is one of the key cellular regulatory systems that ensures this...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#4
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#5
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339119/targeting-of-stress-response-pathways-in-the-prevention-and-treatment-of-cancer
#6
REVIEW
Jaroslav Zelenka, Martina Koncošová, Tomáš Ruml
The hallmarks of tumor tissue are not only genetic aberrations but also the presence of metabolic and oxidative stress as a result of hypoxia and lactic acidosis. The stress activates several prosurvival pathways including metabolic remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis, whose upregulation in tumors is associated with a poor survival of patients, while their activation in healthy tissue with statins, metformin, physical activity, and natural compounds prevents carcinogenesis...
January 12, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29337896/caffeic-acid-and-metformin-inhibit-invasive-phenotype-induced-by-tgf-%C3%AE-1-in-c-4i-and-htb-35-siha-human-cervical-squamous-carcinoma-cells-by-acting-on-different-molecular-targets
#7
Malgorzata Tyszka-Czochara, Malgorzata Lasota, Marcin Majka
During the progression of epithelial cancer, the cells may lose epithelial markers and gain mesenchymal phenotype via Epithelial-Mesenchymal Transition (EMT). Such transformation of epithelial cancer cells to mesenchymal-like characteristic benefits plasticity and supports their ability to migrate. The aim of this study was to evaluate the influence of natural compound Caffeic Acid (CA) alone and in combination with antidiabetic drug Metformin (Met) on metastatic progression of two human cervical squamous cell cancer lines, C-4I and HTB-35/SiHa cells...
January 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#8
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29329345/survival-benefit-associated-with-metformin-use-in-inoperable-non-small-cell-lung-cancer-patients-with-diabetes-a-population-based-retrospective-cohort-study
#9
Min-Chun Chuang, Yao-Hsu Yang, Ying-Huang Tsai, Meng-Jer Hsieh, Yu-Ching Lin, Chin-Kuo Lin, Pau-Chung Chen, Tsung-Ming Yang
OBJECTIVE: To evaluate the effects of metformin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients with diabetes using the Taiwanese National Health Insurance Research Database. RESEARCH DESIGN AND METHODS: In total, 7,620 patients were eligible in this study, among them, 3,578 patients were metformin users and 4,042 were non-users. Propensity score matching was used to reduce possible confounding factors. In total, 4,182 patients (2,091 matched pairs) were included in the matched cohort...
2018: PloS One
https://www.readbyqxmd.com/read/29328467/aspirin-and-metformin-exhibit-antitumor-activity-in-murine-breast-cancer
#10
Maoyuan Zhao, Yuyi Wang, Chi Du, Yanyang Liu, Nan Zhang, Feng Luo
Studies have shown that aspirin and metformin play important roles in chemoprevention and repression of breast cancers, even though the exact mechanism remains unclear. Aspirin is capable of stimulating apoptosis through prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits cell growth by enhancing the tumor suppressive function of transforming growth factor (TGF-β). In the present study, we report a new link between aspirin, metformin, TGF-β1 and murine breast cancer inhibition...
January 4, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29325084/metformin-use-reverses-the-increased-mortality-associated-with-diabetes-mellitus-during-tuberculosis-treatment
#11
Nicholas R Degner, Jann-Yuan Wang, Jonathan E Golub, Petros C Karakousis
Background: The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment. Methods: We conducted a retrospective cohort study comprising patients aged ≥13 years undergoing treatment for culture-confirmed, drug-susceptible pulmonary TB...
January 6, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#12
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320995/metformin-asian-ethnicity-and-risk-of-prostate-cancer-in-type-2-diabetes-a-systematic-review-and-meta-analysis
#13
Christopher B Chen, Maxim Eskin, Dean T Eurich, Sumit R Majumdar, Jeffrey A Johnson
BACKGROUND: Metformin is associated with a reduced risk of some cancers but its effect on prostate cancer is unclear. Some studies suggest only Asians derive this benefit. Therefore, we undertook a systematic review with particular attention to ethnicity. METHODS: Medline, Embase, Scopus, Web of Science, and EBM Reviews were searched from inception to 2015. Two reviewers identified and abstracted articles. Studies were pooled using random effects model and stratified by Western- vs Asian-based populations...
January 10, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29319171/the-key-genes-underlying-pathophysiology-association-between-the-type-2-diabetic-and-colorectal-cancer
#14
Wen-Fang Peng, Feng Bai, Kan Shao, Li-Sha Shen, Hui-Hua Li, Shan Huang
Althoughdiabetes mellitus (DM) is reported as an independent risk factor for colorectal cancer (CRC) in many researches, the underlying pathophysiology is still unclear. We investigated the differentiallyexpressedgenes (DEGs)for the diabetes and CRC to reveal the underlying pathophysiological association between the type 2-diabetic (T2D) and CRC. Gene expression profiles for T2D (GSE55650), CRC (GSE8671) and Metformin treated cell lines (GSE67342) were downloaded from GEO database. The DEGs between T2D samples and their control samples were identified with t-test and variance analysis...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29312591/metformin-sensitizes-lung-cancer-cells-to-treatment-by-the-tyrosine-kinase-inhibitor-erlotinib
#15
Xiaofei Wang, Keqiang Chen, Ying Yu, Yi Xiang, Jae Hong Kim, Wanghua Gong, Jiaqiang Huang, Guochao Shi, Qingyun Li, Min Zhou, Thomas Sayers, Poonam Tewary, Beili Gao, Ji Ming Wang
Lung cancer is one of the deadliest malignant tumors with limited treatment options. Although targeted therapy, using tyrosine-kinase inhibitors such as erlotinib (Erlo), has shown therapeutic benefit, only 15 % patients with mutated epidermal growth factor receptor (EGFR) in lung cancer cells are sensitive. Therefore, additional therapeutic strategy should be developed. In this study, we found that metformin (Met), which is widely used for the treatment of type 2 diabetes (T2D), sensitized lung cancer cells bearing wild-type EGFR to Erlo treatment by enriching cancer cells expressing higher levels of EGFR with persistent phosphorylation...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305964/in-vitro-and-in-vivo-characterization-of-stem-like-cells-from-canine-osteosarcoma-and-assessment-of-drug-sensitivity
#16
Monica Gatti, Agnese Solari, Alessandra Pattarozzi, Chiara Campanella, Stefano Thellung, Lorella Maniscalco, Raffaella De Maria, Roberto Würth, Alessandro Corsaro, Adriana Bajetto, Alessandra Ratto, Angelo Ferrari, Antonio Daga, Federica Barbieri, Tullio Florio
CSC self-renewing and drug resistance cause treatment failure and tumor recurrence. Osteosarcoma is an aggressive bone tumor characterized by biological and molecular heterogeneity, possibly dependent on cancer stem cells (CSCs). CSC identification in osteosarcoma and their efficient targeting are still open questions. Spontaneous canine osteosarcoma shares clinical and biological features with the human tumors, representing a model for translational studies. We characterized three CSC-enriched canine osteosarcoma cultures...
January 3, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29304290/effects-of-metformin-on-insulin-resistance-and-metabolic-disorders-in-tumor-bearing-rats-with-advanced-cachexia
#17
Flaviane de Fatima Silva, Milene Ortiz-Silva, Winny Beatriz de Souza Galia, Priscila Cassolla, Francemilson Goulart da Silva, Maria Fernanda Rodrigues Graciano, Angelo Carpinelli, Helenir Medri de Souza
Metformin (MET) is widely used in the correction of insulin (INS) resistance and metabolic abnormalities in type 2 diabetes. However, its effect on INS resistance and metabolic disorders associated with cancer cachexia is not established. We investigated the MET effects, isolated or associated with INS, on INS resistance and metabolic changes induced by Walker-256 tumor in rats with advanced cachexia. MET (500 mg.kg-1, oral) and MET + INS (NPH, 1.0 IU.kg-1, sc) were administered during 12 days, starting on the day of tumor cell inoculation...
January 5, 2018: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/29303360/flaxseed-lignans-enhance-the-cytotoxicity-of-chemotherapeutic-agents-against-breast-cancer-cell-lines-mda-mb-231-and-skbr3
#18
Yunyun Di, Franklyn De Silva, Edward S Krol, Jane Alcorn
Systemic cytotoxic chemotherapy remains the mainstay of metastatic breast cancer; however, prognosis and overall survival is unfavorable due to inadequate treatment response and/or unacceptable toxicity. Natural compounds and their active metabolites receive increasing attention as possible adjuvant therapy with cancer chemotherapeutics to improve treatment response, survival rates, and quality of life of breast cancer patients. This study investigated the combination of flaxseed lignans (Secoisolariciresinol and Enterolactone) with classic chemotherapeutic agents (Docetaxel, Doxorubicin, and Carboplatin) with different mechanisms of action to determine whether flaxseed lignans could enhance the cytotoxic effect of such drugs in the metastatic breast cancer cell lines, SKBR3 and MDA-MB-231...
January 5, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29285837/the-new-metformin-derivative-hl156a-prevents-oral-cancer-progression-by-inhibiting-the-igf-akt-mtor-pathways
#19
Thuy Giang Lam, Yun Soo Jeong, Soo-A Kim, Sang-Gun Ahn
Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of this study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose dependent manner. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced ROS levels and apoptotic cells with caspase-3 and -9 activation...
December 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285270/metformin-alleviates-nickel-induced-autophagy-and-apoptosis-via-inhibition-of-hexokinase-2-activating-lipocalin-2-in-human-bronchial-epithelial-cells
#20
Yu-Ting Kang, Wen-Cheng Hsu, Chih-Hsien Wu, I-Lun Hsin, Pei-Ru Wu, Kun-Tu Yeh, Jiunn-Liang Ko
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention...
December 1, 2017: Oncotarget
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