scholarly journals Utility of KRAS Gene and Clinicopathological Features in the Assessment of the Risk of Type 2 Diabetes in the Etiology of Colon Cancer

2020 ◽  
Vol 07 (02) ◽  
pp. 035-040
Author(s):  
Wedad Saeed Al-Qahtani ◽  
Ebtesam Al-Olayan ◽  
Fatimah Gh. Albani ◽  
Rania Saad Suliman ◽  
Nada Hamad Aljarba ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Clinicopathological Features ◽  
Mrna Levels ◽  
Kras Gene ◽  
Metastatic Lesions ◽  
Cancer Tissues ◽  
Tremendous Impact

Abstract Background Cancer and diabetes have a tremendous impact on health globally. This study aimed to evaluate the KRAS gene in colon cancer tissues obtained from patients with type 2 diabetes mellitus (T2DM). Materials and Methods Data from 315 cases (156 colon diabetics and 159 patients were nondiabetics) were retrospectively retrieved. mRNA from surgically resected colon cancer tumors were also retrieved. Results The expression of KRAS mRNA was significantly higher in patients afflicted with T2DM than nondiabetic patients. The KRAS mRNA levels were significantly amplified from primary to metastatic lesions (p < 0.001). Conclusion The association between T2DM and colon cancer was well-established in the present study.

Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus

2017 ◽  
Vol 117 (03) ◽  
pp. 529-542 ◽  
Author(s):  
Zsolt Fejes ◽  
Szilárd Póliska ◽  
Zsolt Czimmerer ◽  
Miklós Káplár ◽  
András Penyige ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Platelet Activation ◽  
Mrna Level ◽  
K562 Cells ◽  
Mrna Levels ◽  
Supplementary Material ◽  
Calpain Inhibition

SummaryMegakaryocyte (MK)-derived miRNAs have been detected in platelets. Here, we analysed the expression of platelet and circulating miR-223, miR-26b, miR-126 and miR-140 that might be altered with their target mRNAs in type 2 diabetes mellitus (DM2). MiRNAs were isolated from leukocyte-depleted platelets and plasma samples obtained from 28 obese DM2, 19 non-DM obese and 23 healthy individuals. The effect of hyperglycaemia on miRNAs was also evaluated in MKs using MEG-01 and K562 cells under hyperglycaemic conditions after 8 hours up to four weeks. Quantitation of mature miRNA, pre-miRNAs and target mRNA levels (P2RY12 and SELP) were measured by RT-qPCR. To prove the association of miR-26b and miR-140 with SELP (P-selectin) mRNA level, overexpression or inhibition of these miRNAs in MEG-01 MKs was performed using mimics or anti-miRNAs, respectively. The contribution of calpain substrate Dicer to modulation of miRNAs was studied by calpain inhibition. Platelet activation was evaluated via surface P-selectin by flow cytometry. Mature and pre-forms of investigated miRNAs were significantly reduced in DM2, and platelet P2RY12 and SELP mRNA levels were elevated by two-fold at increased platelet activation compared to controls. Significantly blunted miRNA expressions were observed by hyperglycaemia in MEG-01 and K562-MK cells versus baseline values, while the manipulation of miR-26b and miR-140 expression affected SELP mRNA level. Calpeptin pretreatment restored miRNA levels in hyperglycaemic MKs. Overall, miR-223, miR-26b, miR-126 and miR-140 are expressed at a lower level in platelets and MKs in DM2 causing upregulation of P2RY12 and SELP mRNAs that may contribute to adverse platelet function.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals The Activation of ERK1/2 and JNK MAPK Signaling by Insulin/IGF-1 Is Responsible for the Development of Colon Cancer with Type 2 Diabetes Mellitus

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149822 ◽  
Author(s):  
Jia-An Teng ◽  
San-Gang Wu ◽  
Jia-Xin Chen ◽  
Qiang Li ◽  
Fang Peng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Type 2 Diabetes Mellitus ◽  
Mapk Signaling

scholarly journals The Prevalence of Coronary Heart Disease, Stroke and Selected Co-Morbidities in Patients with Newly Diagnosed Type 2 Diabetes Population - Based on Cohort Study of Outpatients

2013 ◽  
Vol 13 (1) ◽  
pp. 33-43
Author(s):  
Linda Bukova ◽  
P. Galajda ◽  
M. Mokan
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Elevated Serum ◽  
Newly Diagnosed ◽  
Prevalence Of Cancer ◽  
Cancer Diseases

Abstract The prospective study analyses prevalence of coronary heart disease, stroke, elevated serum levels of ALT and GGT and prevalence of cancer diseases in patients with newly diagnosed type 2 diabetes mellitus, and usage of this epidemiological data in everyday clinical practice. Outpatients with newly diagnosed type 2 diabetes mellitus were monitoring during the period of August 2007 - August 2011. The patients with previously treated type 2 diabetes mellitus were eliminated from the monitoring. The population consists of 117 males and 83 females aged 30 to 92 years sent by GPs and various specialists. The relatively low prevalence of known coronary artery disease was recorded in men (34%) and in women (19%). Prevalence of stroke history was confirmed in 12% of men and 7% of women. The elevated serum ALT levels > 0.55 μkat/l was recorded in 45% of men and 45% of women and elevated serum GGT levels > 0.45 μkat/l was recorded in 81% of men and 68% of women. Prevalence of cancer diseases was recorded 5% in women and 5.26% of men. In the studied group of patients there was recorded the occurrence of colon cancer in men over 64 years old and the occurrence of breast cancer, endometrial cancer and colon cancer in women over 62 years old.

scholarly journals Greater Development of 1, 2-Dimethylhydrazine-induced Colon Cancer in a Rat Model of Type 2 Diabetes Mellitus

2006 ◽  
Vol 34 (4) ◽  
pp. 385-389 ◽  
Author(s):  
K Terai ◽  
K Sakamoto ◽  
M Goto ◽  
M Matsuda ◽  
S Kasamaki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model

scholarly journals Dapagliflozin Inhibits Cell Adhesion to Collagen I and IV and Increases Ectodomain Proteolytic Cleavage of DDR1 by Increasing ADAM10 Activity

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 495 ◽  
Author(s):  
Junichi Okada ◽  
Eijiro Yamada ◽  
Tsugumichi Saito ◽  
Hideaki Yokoo ◽  
Aya Osaki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Type 2 Diabetes Mellitus ◽  
Cell Adhesion ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Hct116 Cells

Dapagliflozin, empagliflozin, tofogliflozin, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2), is used clinically to reduce circulation glucose levels in patients with type 2 diabetes mellitus by blocking the reabsorption of glucose by the kidneys. Dapagliflozin is metabolized and inactivated by UGT1A9. Empagliflozin is metabolized and inactivated by UGT1A9 and by other related isoforms UGT2B7, UGT1A3, and UGT1A8. Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3. Dapagliflozin treatment of HCT116 cells, which express SGLT2 but not UGT1A9, results in the loss of cell adhesion, whereas HepG2 cells, which express both SGLT2 and UGT1A9, are resistant to the adhesion-related effects of dapagliflozin. PANC-1 and H1792 cells, which do not express either SGLT2 or UGT1A9, are also resistant to adhesion related effects of dapagliflozin. On the other hand, either empagliflozin or tofogliflozin treatment of HCT116, HepG2, PANC-1, and H1792 cells are resistant to the adhesion-related effects as observed in dapagliflozin treated HCT116 cells. Knockdown of UGT1A9 by shRNA in HepG2 cells increased dapagliflozin sensitivity, whereas the overexpression of UGT1A9 in HCT116 cells protected against dapagliflozin-dependent loos of cell adhesion. Dapagliflozin treatment had no effect on cellular interactions with fibronectin, vitronectin, or laminin, but it induced a loss of interaction with collagen I and IV. In parallel, dapagliflozin treatment reduced protein levels of the full-length discoidin domain receptor I (DDR1), concomitant with appearance of DDR1 cleavage products and ectodomain shedding of DDR1. In line with these observations, unmetabolized dapagliflozin increased ADAM10 activity. Dapagliflozin treatment also significantly reduced Y792 tyrosine phosphorylation of DDR1 leading to decrement of DDR1 function and detachment of cancer cells. Concomitant with these lines of results, we experienced that CEA in patients with colon cancer, which express SGLT2 but not UGT1A9, and type 2 diabetes mellitus treated by dapagliflozin in addition to chemotherapy was decreased (case 1). CEA in patients with colon cancer, which express SGLT2 but not UGT1A9, and type 2 diabetes mellitus was treated by dapagliflozin alone after radiation therapy was decreased but started to rise after cessation of dapagliflozin (case 2). CA19-9 in two of patients with pancreatic cancer and type 2 diabetes mellitus was resistant to the combination therapy of dapagliflozin and chemotherapy (case 3 and 4 respectively). PIVKAII in patients with liver cancer and type 2 diabetes mellitus, and CYFRA in patients with squamous lung cancer and type 2 diabetes mellitus was also resistant the combination therapy of dapagliflozin and chemotherapy (case 5 and 6 respectively). Taken together, these data suggest a potential role for dapagliflozin anticancer therapy against colon cancer cells that express SGLT2, but not UGT1A9.

Less Advanced Stages of Colon Cancer in Patients with Type 2 Diabetes Mellitus: an Unexpected Finding?

2012 ◽  
Vol 120 (04) ◽  
pp. 224-228 ◽  
Author(s):  
J. Nagel ◽  
S. Bücker ◽  
M. Wood ◽  
R. Stark ◽  
B. Göke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Colon Cancer ◽  
Type 2 Diabetes Mellitus ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Lower Risk ◽  
Advanced Stages

AbstractEpidemiological studies have found an increased risk for colon cancer and faster disease progression in patients with type 2 diabetes mellitus (T2DM). We aimed to determine whether patients with T2DM are diagnosed with more advanced stages of colorectal cancer, i. e., metastasized disease (UICC III and IV), at the time of diagnosis, since such a finding may have an impact on future guidelines for patients with T2DM.A cross-sectional analysis of colorectal cancer patients was performed. Stages at diagnosis in patients with (18.0%) or without (82%) T2DM were compared using logistic regression analysis to correct for confounders.Patients with T2DM were older, more obese, and more often male (each p<0.05). Unexpectedly, patients with T2DM had a lower risk for metastasized disease at diagnosis (p=0.023). Correction for age, gender, BMI, smoking and aspirin intake in a multiple logistic regression analysis did not change the result (OR=0.57, p=0.037). When looking at individual cancer stages rather than collapsed categories, there was a trend for less advanced stages in patients with T2DM (p=0.093). Excluding stage I because of potential screening bias due to the introduction of (insurance-covered) colonoscopy screening improved model fit, and confirmed less advanced cancer stages (p=0.0246).Possibly because of earlier detection, patients with T2DM may be at lower risk for advanced stages of colon cancer at diagnosis. Further studies are warranted to confirm our results and to investigate the impact of closer medical surveillance in patients with type 2 diabetes mellitus.

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