Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Midkine (MK) is a secreted heparin-binding growth factor. Several types of human cancer have increased MK expression with elevated serum levels. The purpose of this study was to determine whether MK was expressed in endometrial carcinoma and to evaluate the clinicopathological significance of serum MK in patients with endometrial carcinoma. Immunohistochemical expression of MK was evaluated in 85 endometrial carcinoma samples and 33 controls. MK expression was significantly higher in the carcinomas than in normal endometrium (P < 0.001). Interestingly, MK expression was highest at the margins of invasion and low in the superficial areas of the tumor samples. Using ELISA, we compared serum MK concentration in 120 endometrial carcinoma patients with the concentration in 46 patients with benign gynecologic tumors. Serum MK value in patients with cancer was significantly higher than that in the patients with benign diseases (P = 0.01). Patients with positive lymph node metastasis or recurrence, or cancer death, had a higher serum MK level (P = 0.008, P = 0.009, respectively). In conclusion, MK immunoreactivity in endometrial carcinoma is significantly higher than in normal endometrium. Additionally, preoperative serum MK levels are significantly correlated with prognosis and the presence of lymph node metastasis. Thus, MK may be a useful serum biomarker for identifying high risk patients of endometrial carcinoma.
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PMID:Midkine and its clinical significance in endometrial carcinoma. 1842 45

Metformin, a drug widely used in the treatment of type II diabetes mellitus (T2DM), has been the focus of interest as a potential therapeutic agent for certain types of malignancies, including gynaecological cancers [i.e. endometrial cancer (EC)]. Although the exact mechanism behind the potential anticancer activity of metformin is still not completely understood, certain studies have suggested that different effects on cell functions, such as inhibition of cell migration, apoptosis and tumor cell proliferation, are involved in its preventive and therapeutic effects in certain types of malignancies, including EC. In contrast, midkine (MK), a heparin-binding growth factor and cytokine, which induces carcinogenesis and chemoresistance, promotes the development and progression of many malignant tumours by increasing diverse cell functions such as cell proliferation, cell survival and antiapoptotic activities via mainly the activation of phosphatidyl inositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. The same pathways are also subject to certain therapeutic effects of metformin, although this cytokine and this drug have some different mechanism of action pathways as well. Taken together, MK and metformin appear to have opposite effects in various biological processes such as apoptosis, cell proliferation, cell survival, cell migration, and angiogenesis. On the other hand, MK activates PI3K and MAPK cell signal pathways, whereas metformin inhibits these two pathways. It seems likely that almost all the pathways and cell functions, which play important roles in malignancies, are inhibited by metformin and activated by MK. Given the opposite relationship between the actions of metformin and MK, we hypothesize that metformin may act like a novel MK inhibitor in some malignancies. We also discuss the possible relationship between metformin and MK in the context of EC, the most common gynecological cancer worldwide, which incidence is rising rapidly, in parallel with the increase in obesity, T2DM and insulin resistance. In this respect, the therapeutic use of metformin may improve the survival of EC or other cancers, via inhibiting or overcoming the unwanted effects of MK in carcinogenesis.
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PMID:Inhibition of midkine by metformin can contribute to its anticancer effects in malignancies: A proposal mechanism of action of metformin in context of endometrial cancer prevention and therapy. 3163 70