SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer.

Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

Genetic disposition and modifiable factors independently associated with anemia in patients with type 2 diabetes mellitus.

AIMS: Anemia is prevalent but under-recognized in patients with diabetes mellitus (DM). Genetic variants in angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-α) and erythropoietin (EPO) have been associated with diabetic nephropathy. In the present study, we investigated the associations between anemia and polymorphisms in EPO promoter (rs1617640), TNF-α G-308A and ACE Insertion/Deletion in Chinese patients with type 2 diabetes. METHODS: Polymorphisms in ACE, TNF-α and EPO were genotyped in 1142 patients. Anemia was defined as hemoglobin (Hb) levels below 12 g/dL for women and 13 g/dL for men. RESULTS: 286 (25%) patients had anemia. Patients with anemia were older, had longer duration of diabetes, worse renal function and more albuminuria. ACE Insertion/Deletion and TNF-a G-308A were not associated with anemia. The frequencies of EPO polymorphism (rs1617640) were significantly different between anemic and nonanemic patients. Patients with TT genotype had higher prevalence of anemia than those with TG and GG. Regression analysis identified EPO SNP, duration of DM, serum albumin, albuminuria and renal function independently associated with anemia. After adjusting for multiple variables, TT and TG genotypes were associated with 3-5-fold increased risk for anemia compared to GG. CONCLUSIONS: The EPO genotype in Chinese patients with type 2 diabetes is associated with anemia and may help to identify those at risk. Further evaluation of its effect on clinical outcomes in prospective studies may be useful to predict the outcomes of erythropoiesis stimulating therapy, and to individualize anemia management.

Prevalence of overactive bladder and associated risk factors in 1359 patients with type 2 diabetes.

OBJECTIVE: To evaluate overactive bladder (OAB, dry and wet) and the associated risk factors of OAB wet (with incontinence) in type 2 diabetes. METHODS: A self-administered questionnaire containing the OAB symptom score (OABSS, 0-15, with higher numbers indicating an increasing severity of symptoms) was obtained from subjects with type 2 diabetes at a dedicated diabetic center. The association of age, sex, duration of diabetes, body mass index, waist circumference, glycated hemoglobin level, high-sensitive C-reactive protein level, and diabetes-associated complications to the risk of OAB and OAB wet was evaluated. RESULTS: Of 1359 consecutive subjects, 22.5% reported having OAB, with 11.7% reporting OAB dry and 10.8% OAB wet. The difference in symptom severity was statistically significant among those without OAB and those with OAB dry and OAB wet (OABSS 2.5 ± 1.4, 5.9 ± 1.6, and 8.9 ± 2.6, respectively). The prevalence of OAB and OAB wet was 2.4-fold and 4.2-fold greater, respectively, in patients with a diabetes duration >10 years and age >50 years. Age and male sex and age and waist circumference were independent risk factors for OAB and OAB wet, respectively, after multivariate analysis. Glycated hemoglobin and high-sensitivity C-reactive protein levels were similar between patients with diabetes patients with and without OAB. CONCLUSION: In the dedicated diabetic center in which all patients were screened, 22.5% had OAB, and 48.0% of those with OAB had incontinence. These findings can help guide the collaboration between urologists and diabetologists to work toward developing screening for, and early treatment of, urologic complications in higher risk patients.