Cancer biology in diabetes

Shi, Sen; He, Yanzheng; Koya, Daisuke; Kanasaki, Keizo

doi:10.1111/jdi.12208

Cited by 27 publications

(40 citation statements)

References 179 publications

(241 reference statements)

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“…An increase in site-specific cancer incidence associated with diabetes mellitus has also been described in a number of systemic reviews and meta-analyses (1)(2)(3)(4)(5)(6). Although the mechanisms underlying this association are yet to be investigated, the most frequently proposed hypothesis is the effect of insulin resistance with secondary hyperinsulinemia, since insulin may exert mitogenic effects via the insulin-like growth factor-1 (IGF1) receptor (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…AMPK is a cellular energy sensor located within the cytoplasm, which is involved in the regulation of metabolism within cells (2,(21)(22)(23). Metformin reduces adenosine triphosphate (ATP) production, resulting in an increased AMP:ATP ratio, which leads to activation of the liver kinase B1 (LKB1)-AMPK signaling pathway (2,(21)(22)(23) (2,(24)(25)(26).…”

Section: Metformin Mechanism Of Actionmentioning

confidence: 99%

“…Metformin, a biguanide frequently used in the treatment of type 2 diabetes, has been demonstrated to exert marked chemopreventative and antiproliferative effects against various types of cancer (1,2,(15)(16)(17)(18)(19)(20). Metformin is able to inhibit cell growth via insulin and non-insulin dependent mechanisms (1,2,(15)(16)(17), while enhancing insulin receptor sensitivity, increasing insulin uptake and therefore reducing systemic insulin levels.…”

Section: Introductionmentioning

confidence: 99%

“…Metformin is able to inhibit cell growth via insulin and non-insulin dependent mechanisms (1,2,(15)(16)(17), while enhancing insulin receptor sensitivity, increasing insulin uptake and therefore reducing systemic insulin levels. Metformin is also able to inhibit cell proliferation via activation of the growth inhibitory adenosine monophosphate-activated protein kinase (AMPK).…”

Section: Introductionmentioning

confidence: 99%

“…Metformin is also able to inhibit cell proliferation via activation of the growth inhibitory adenosine monophosphate-activated protein kinase (AMPK). AMPK blocks signaling via the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways, downstream of the insulin and IGF1 receptors (2,15,16).…”

Section: Introductionmentioning

confidence: 99%

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Clinical benefits of metformin in gynecologic oncology

2015

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Section: Introductionmentioning

confidence: 99%

Section: Metformin Mechanism Of Actionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical benefits of metformin in gynecologic oncology

2015

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High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation

Huang

Jia

et al. 2016

Breast Cancer Res Treat

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Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis. This work indicates a prospective utilization of HDL-based strategies in the treatment of breast cancer patients with type 2 diabetes.

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In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin

et al. 2019

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Vildagliptin and sitagliptin are commonly used antidiabetic drugs. Chromosomal aberration (CA), sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays were employed to assess and compare cytotoxic and genotoxic effects of these drugs. Peripheral lymphocytes were exposed to 125 lg/ml, 250 lg/ml and 500 lg/ml of vildagliptin and 250 lg/ml, 500 lg/ml and 1000 lg/ml of sitagliptin for 24 h and 48 h with and without exogenous metabolic activation. At the end of the study, it was determined that these drugs and their metabolites had no genotoxic effects on CA, SCE and CBMN. On the other hand, parallel to the increase in dose, vildagliptin showed weak cytotoxicity on the mitotic index, and depending on its increase in dose; sitagliptin caused potential cytotoxicity and cytostatic effect on the mitotic index, nuclear division index and proliferation index. Due to their cytotoxic and cytostatic potential, these drugs inhibit cell proliferation.

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Cancer biology in diabetes

Cited by 27 publications

References 179 publications

Clinical benefits of metformin in gynecologic oncology

Clinical benefits of metformin in gynecologic oncology

High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM-1 and VCAM-1 upregulation

In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin

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