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It has been recently demonstrated that the use of metformin as an insulin sensitizer reduces incidence, progression and even mortality through cancer Evans JM et al. A significant number of studies mention the beneficial effect that metformin has on the treatment and prognosis of certain neoplastic localizations mammary, pancreas, colorectal, hepaticmost frequently by interfering with endometrial cancer jco cycle regulation.

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Thus, the study of the effects of oral anti-diabetic drugs is worth being continued, as they can bring multiple benefits endometrial cancer jco administered oncological treatments.

Recent, s-a endometrial cancer jco că utilizarea metforminului endometrial cancer jco agent de sensibilizare la insulină reduce incidența, progresia și chiar mortalitatea prin cancer Evans JM et al. Un număr sem­ni­ficativ de studii menționează efectul benefic pe care met­forminul îl are asupra tratamentului și prognosticului anumitor localizări neoplazice mamare, pancreas, colorectal, hepaticcel mai frecvent prin interferența cu reglarea ciclului celular.

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Astfel, studiul efectelor medicamentelor antidiabetice orale merită să fie continuat, deoarece acestea pot aduce beneficii endometrial cancer jco tratamentelor oncologice administrate. A significant number of cancers are attributed to the sedentary lifestyle that entails the early appearance of metabolic syndrome and insulin resistance, along with the onset of diabetes, cardiovascular disease and cancer.

Hyperinsulinism negatively affects the prognosis of oncological patients and is an independent risk factor for several types of cancers, thus explaining the frequent association of obesity with neoplasia.

Insulin can promote cancerogenesis by the direct effect on epithelial tissues endometrial cancer jco act on the insulin receptor family Belfiore et al. Recent evidence indicates that the abnormally high level of proliferative activity of premalignant and malignant cells requires high levels of nutrients to meet increased energy demand and protein biosynthesis demands Vander Heiden M. Metformin is a widely used oral antidiabetic agent in the treatment of type 2 diabetes mellitus, where it is commonly used as endometrial cancer jco insulin sensitizer since it has not only a function of lowering blood sugar, but also of reducing insulin resistance associated by hyperinsulinemia.

This medicine acts as a growth inhibitor, rather than an insulin sensitizer with respect to epithelial cells Zakikhani M.

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It has been recently demonstrated that the use of metformin as an endometrial cancer jco sensitizer reduces incidence, progression and even mortality through cancer Evans J.

Regarding the direct effects of metformin, LKB1, which is a downstream signaling molecule in the AMPK pathway, functions as a tumor suppressor protein p.

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Thus, AMPK-induced metformin activation could lead to increased LKB1-mediated tumor suppression which would directly inhibit cell proliferation and colony formation and promote partial cell cycle arrest in cancer cell lines Alinova et al. Metformin can exert similar antineoplastic effects through an indirect mechanism: metformin activates the AMPK pathway in hepatocytes and skeletal muscles.

Thus, it inhibits hepatic gluconeogenesis and glucose efflux from skeletal muscles and consequently reduces circulating glucose and insulin concentrations, both contributing to cancerogenesis Shaw R.

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Metformin is the first option in the treatment of type 2 diabetes mellitus, prescribed as a single agent for patients in the initial stage endometrial cancer jco the disease, or in combination with other oral antidiabetics in patients with advanced disease Kowall B. Metformin endometrial cancer jco been shown to reduce the incidence endometrial cancer jco type 2 diabetes in patients at high risk Knowler W.

Impactul metforminului în tratamentul şi evoluţia pacienţilor oncologici cu diabet zaharat de tip 2

It is an inexpensive and well tolerated drug, whose side effects are very rare, which determine its widespread use. The warts foot problems that the use of metformin is associated with a decrease in malignancy risk for certain organs can be explained by the fact that metformin works by using the nutrients needed to produce a new cell, starting from a proliferative cell Vander Heiden M. Metformin appears to be associated with a decrease of cancer risk in the colon, pancreas and mammary gland, because diabetes or elevated blood glucose and insulin levels play an important role in the development of these types of tumors Xue F.

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Regarding colon cancer, it has been shown that metformin potentiates the effects of hypercaloric nutrition that stimulate tumor growth Zakikhani M.

In the case of mammary gland neoplasm, it was observed that diabetic patients treated with metformin had a higher rate of complete response to neoadjuvant chemotherapy than the patients treated with other types of antidiabetic agents.

In patients differentiated by many variables - Body Mass Index, stage of the disease, degree of tumor differentiation, HER2 status, estrogen and progesterone receptors, age and use of neoadjuvant treatment with taxanes, metformin remained an independent predictor of the therapeutic response.

The use of metformin endometrial cancer jco a much better predictor than certain tumor characteristics, including differentiation, hormone receptor status, or overexpression of HER2 neu Goodwin P. Breast cancer cells can be protected against growth inhibition induced by metformin by diminishing RNA against Endometrial cancer jco.

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This demonstrates that metformin-activated AMP-kinase, recently demonstrated to be necessary for the metformin inhibition of gluconeogenesis in hepatocytes, is also involved in the metformin-induced growth inhibition of epithelial cells Zakikhani M.

In the case of patients diagnosed with bronchopulmonary neoplasm, whose frequency is significant with associated type 2 diabetes mellitus, it has been shown that their response to treatment is influenced by metformin by increasing sensitivity to external irradiation, endometrial cancer jco that irradiation is a known inducer of AMPK, and metformin can modulate this effect, thus improving the response to radiotherapy.

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This hypothesis was tested using cell lines from the breast, lung and prostate. It has also been demonstrated that metformin increases sensitivity to ionizing radiation, increase assessed by increasing the duration of irradiation after exposure to 2 Gy, supporting this hypothesis Sanli T.

According to some studies, in human papilloma treatment with non-small cell lung cancer and type 2 diabetes mellitus, chemotherapy in combination with metformin increased the survival rate compared to the same chemotherapy, but in combination with insulin or other oral anti-diabetic treatments 8.

The use of metformin as a prevention and treatment agent endometrial cancer jco certain neoplastic locations has also gained considerable interest in hepatic neoplasms, due to the increased frequency of diabetes associated with this type of cancer.

Some studies thus confirm the improvement in survival rate of patients with primitive hepatic neoplasms associated with type 2 diabetes and treated with metformin Shu-Juan Ma et al.

A significant number of studies on pancreatic neoplasm and the treatment of type 2 diabetes discuss the effect that metformin has on inhibiting the cell proliferation, migration and invasion process by destroying endometrial cancer jco stem cells, intervening at the microRNA level. Oral administration of metformin in diabetic patients suffering from pancreatic neoplasm increased the prognosis of oncologic treatment in these patients.

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Studies in diabetic patients treated with different classes of oral endometrial cancer jco agents wart mouth picture shown a lower risk of developing pancreatic adenocarcinoma if the anti-diabetic treatment was metformin Yu-Yang, Also, in the case of rectal neoplasm, as well as the aforementioned neoplastic localizations, the studies conducted so far associate the use of metformin with a low rate of appearance of this type of neoplasia.

Endometrial cancer jco well as for the bronchopulmonary neoplasm, the mechanism of action of metformin coincides with that from colorectal neoplasm.

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The study of metformin role as an oral antidiabetic in the management of neoplastic disease in patients with type 2 diabetes is particularly important and requires further consideration, given the studies that perpetuate endometrial cancer jco idea that endometrial cancer jco reduces inflammation and prevents cancer development, or potentiates oncological treatment where the oncological disease has already papillomatosis cutis lymphatic. Bibliografie 1.

Economic costs of diabetes in the U. Diabetes Care ; 31 3 — Alimova IN et al. Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Endometrial cancer jco ; 8 6 — Endocr Rev ; — CAPR, March Bowker SL et al. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin: response to Farooki and Schneider.

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Diabetes Care ; 29 8 —1. Management of colorectal cancer and diabetes, J R Soc Med.

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Evans JM et al. Metformin and reduced risk of cancer in diabetic patients. BMJ ; —5.

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Metmorfin in breast cancer: time to action, Journal of Clinical Oncology 27, no. Are sulfonylurea and insulin therapies associated with a larger risk of cancer than metformin therapy? A retrospective database analysis. Diabetes Care, endometrial cancer jco 159— Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med ; — Diabetes Prevention Program Research Group. Lancet ; — Insulin-like growth factors and neoplasia.

Impactul metforminului în tratamentul şi evoluţia pacienţilor oncologici cu diabet zaharat de tip 2

Nat Rev Cancer ; — Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer ; 8 12 — Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol ; 6: — Mahvash Zakikhani, Ryan Dowling, I.

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Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells, doi: CAN, November Int J Radiat. Shaw RJ et al.

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The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science ; —6. Cancer, — Understanding the Warburg effect: the metabolic requirements of cell proliferation.

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Science ; — Xue F, Michels KB. Diabetes, metabolic syndrome, and breast cancer: a review of the current endometrial cancer jco. Am J ClinNutr ; s— Yu—Xiao Yang.

Cancerul — factori de risc 4 februarie Conform National Cancer Institute NIH , se considera ca principalii factori de risc ai cancerului sunt: vârsta, anumite substante din mediu, dieta, activitatea fizică, factorii infecțioși, masa grasă şi greutatea corporală, radiațiile solare şi fumatul [1]. Vârsta Înaintarea în vârstă este considerat ca fiind cel mai important factor de risc, atat pentru cancer, în general, cat şi pentru multe tipuri individuale de cancer. Un sfert din cazurile noi de cancer se descoperă între ani [1].

Gastroenterology, VolumeIssue 2, Augustpages The effects of adiponectin and metformin on prostate and colon neoplasia involve activation of AMP activated protein kinase.

Cancer Prev Res Phila ; — Diabetes mellitus and breast cancer. Lancet Oncol ; — WHO,