Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary energy restriction has been shown to repress both mammary tumorigenesis and aggressive mammary tumor growth in animal studies. Metformin, a caloric restriction mimetic, has a long history of safe use as an insulin sensitizer in diabetics and has been shown to reduce cancer incidence and cancer-related mortality in humans. To determine the potential impact of dietary energy availability and metformin therapy on aggressive breast tumor growth and metastasis, an orthotopic syngeneic model using triple negative 66cl4 tumor cells in Balb/c mice was employed. The effect of dietary restriction, a standard maintenance diet or a diet with high levels of free sugar, were tested for their effects on tumor growth and secondary metastases to the lung. Metformin therapy with the various diets indicated that metformin can be highly effective at suppressing systemic metabolic biomarkers such as IGF-1, insulin and glucose, especially in the high energy diet treated animals. Long-term metformin treatment demonstrated moderate yet significant effects on primary tumor growth, most significantly in conjunction with the high energy diet. When compared to the control diet, the high energy diet promoted tumor growth, expression of the inflammatory adipokines leptin and resistin, induced lung priming by bone marrow-derived myeloid cells and promoted metastatic potential. Metformin had no effect on adipokine expression or the development of lung metastases with the standard or the high energy diet. These data indicate that metformin may have tumor suppressing activity where a metabolic phenotype of high fuel intake, metabolic syndrome, and diabetes exist, but may have little or no effect on events controlling the metastatic niche driven by proinflammatory events.
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PMID:Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy. 2020 98

The prognosis of pancreatic cancer remains dismal, with little advance in chemotherapy because of its high frequency of chemoresistance. Metformin is widely used to treat type II diabetes, and was shown recently to inhibit pancreatic cancer stem cell proliferation. In the present study, we investigated the role of metformin in chemoresistance of pancreatic cancer cells to gemcitabine, and its possible cellular and molecular mechanisms. Metformin increases sensitivity of pancreatic cancer cells to gemcitabine. The mechanism involves, at least in part, the inhibition of CD133(+) cells proliferation and suppression of P70S6K signaling activation via inhibition of ERK phosphorylation. Studies of primary tumor samples revealed a relationship between P70S6K signaling activation and the malignancy of pancreatic cancer. Analysis of clinical data revealed a trend of the benefit of metformin for pancreatic cancer patients with diabetes. The results suggested that metformin has a potential clinical use in overcoming chemoresistance of pancreatic cancer.
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PMID:Metformin Increases Sensitivity of Pancreatic Cancer Cells to Gemcitabine by Reducing CD133+ Cell Populations and Suppressing ERK/P70S6K Signaling. 2639 Nov 80

Observational studies have demonstrated that metformin use in diabetic patients is associated with reduced cancer incidence and mortality. Here, we aimed to determine whether metformin use was associated with improved survival in patients with resected pancreatic cancer. All patients with diabetes who underwent resection for pancreatic adenocarcinoma between 12/1/1986 and 4/30/2013 at our institution were categorized by metformin use. Survival analysis was done using the Kaplan-Meier method, with log-rank test and Cox proportional hazards multivariable regression models. For analyses of our data and the only other published study, we used Meta-Analysis version 2.2. We identified 44 pancreatic cancer patients with diabetes who underwent resection of the primary tumor (19 with ongoing metformin use, 25 never used metformin). There were no significant differences in major clinical and demographic characteristics between metformin and non-metformin users. Metformin users had a better median survival than nonusers, but the difference was not statistically significant (35.3 versus 20.2 months; P = 0.3875). The estimated 2-, 3-, and 5-year survival rates for non-metformin users were 42%, 28%, and 14%, respectively. Metformin users fared better with corresponding rates of 68%, 34%, and 34%, respectively. In our literature review, which included 111 patients from the two studies (46 metformin users and 65 non-users), overall hazard ratio was 0.668 (95% CI 0.397-1.125), with P = 0.129. Metformin use was associated with improved survival outcomes in patients with resected pancreatic cancer, but the difference was not statistically significant. The potential benefit of metformin should be investigated in adequately powered prospective studies.
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PMID:Effect of Metformin Use on Survival in Resectable Pancreatic Cancer: A Single-Institution Experience and Review of the Literature. 2696 62