Expression of cyclooxygenase-2 in cholangiocarcinoma: correlation with clinicopathological features and prognosis

BACKGROUND AND AIMS: No information is available on the nature of the correlation between cyclooxygenase-2 (COX-2) expression and the clinicopathological features and prognosis of cholangiocarcinoma (CC). The goal of the present study was to determine the possible roles and clinical significance of COX-2 expression in CC. METHODS: We investigated the immunohistochemical expression of COX-2 in 102 patients with CC with respect to clinicopathological characteristics, namely evidence of Clonorchis sinensis infection, proliferation index (PI, assessed by Ki-67 expression), apoptotic index (AI, assessed by TUNEL stain), and microvessel density (MVD, assessed by CD34 expression). Evidence of C. sinensis infection was assessed by the microscopic examination of stools for C. sinensis ova, serological testing (ELISA), and the detection of peripheral bile duct dilations by imaging studies. RESULTS: An immunohistochemical investigation demonstrated the immunolabeling of tumor cells, mainly in the cytoplasmic and perinuclear regions, in 53 (52%) of the 102 patients with CC. No significant differences were found in terms of age, sex, tumor differentiation, involvement of the resection margin, presence of lymph nodes or liver metastases, or in pTNM stage between COX-2 positive and COX-2 negative patients. However, evidence of C. sinensis infection was more common in COX-2 positive patients (P < 0.05). No significant differences were found for PI, AI, MVD, or cumulative survival between COX-2 positive and COX-2 negative patients. CONCLUSION: Clonorchis sinensis infection is related to aberrant COX-2 expression in patients with CC. However, COX-2 expression is not related to clinical outcome in CC patients.     

Staged diabetes management according to individual patient insulin resistance and beta-cell function ameliorates glycaemic control in type 2 diabetes mellitus

Objective The current consensus algorithm for management of type 2 diabetes is based on the fasting glucose concentration and glycated haemoglobin A_1c (HbA_1c) level. We applied a new therapeutic strategy by assessing insulin secretion and insulin resistance, in addition to glucose concentrations in individual patients. Design and patients We enrolled 193 patients with type 2 diabetes. The patients were assigned to one of six groups according to insulin secretion measured by the serum fasting C‐peptide concentration and insulin resistance measured by an insulin tolerance test (ITT). The two groups were treated differently: 108 patients were treated using a new staged diabetes management (SDM) strategy and 85 patients continued with conventional therapy. Measurements We compared metabolic variables in the two groups at baseline and 12 months after enrolment. Results In patients treated with the SDM strategy, fasting glucose concentration decreased from 9·8 ± 2·1 to 8·2 ± 1·7 mmol/l (P < 0·001). Postprandial 2‐h glucose concentration decreased from 14·19 ± 3·34 to 12·27 ± 3·24 mmol/l (P < 0·001). HbA_1c level decreased from 8·37 ± 1·42% to 7·72 ± 1·39% (P < 0·001). About 43% of the new SDM group achieved an HbA_1c of < 7·0% compared with 25% of patients in the conventional treatment group. Conclusions The new SDM strategy, based on individual data on insulin resistance and insulin secretion, may provide valuable clinical benefits in non‐obese Korean patients with type 2 diabetes.     

The HLA-G Genetic Contribution to Bipolar Disorder: A Trans-Ethnic Replication

Bipolar disorder (BD) is frequently associated with immune dysfunctions. Studying the genetic diversity of the immuno-modulatory human leukocyte antigen (HLA)-G locus in a French BD cohort, we previously reported an association between a functionally relevant 14 bp Ins/Del polymorphism and BD risk. The present study investigated the genetic and expression diversities of HLA-G in a geographically distinct South Indian population-group BD patients, as well as the influence of exposure to the neurotropic Toxoplasma gondii pathogen. Three functionally relevant HLA-G polymorphisms, i.e. HLA-G 14 bp Ins/Del (rs66554220), +3142G>C (rs1063320) and +3187A>G (rs9380142) were genotyped by polymerase chain reaction (PCR) and real-time PCR. Sub-samples of BD patients and healthy controls (HC) were investigated for plasma levels of soluble HLA-G (sHLA-G) isoforms, as well as circulating stigma of T. gondii infection.

Findings indicate: (i) the frequency of the HLA-G 14 bp Del/Del genotype was higher in BD cases, as compared to HC; (ii) the HLA-G + 3142 C allele and CC genotype were more prevalent in BD patients than in HC; (iii) sHLA-G levels were significantly higher in BD cases, especially in females and in the early onset sub-group; and (iv) the InsGA haplotype was more prevalent in HC.

Our findings further support the genetic contribution of HLA-G to BD risk, as well as indicate relevant expression profiles. Such data may also indicate a potential developmental role in BD etiology, given that HLA-G is an important immune regulator from the intrauterine period and across development.