Microsatellite mapping of a susceptible locus within the HLA region for Behçet's disease using Jordanian patients

Beh?et's disease (BD) has been established to be associated with HLA-B51. However, it has not been revealed whether the HLA-B51 gene itself or another gene located near the HLA-B gene is directly involved in the pathogenesis of BD. Previously, using Japanese BD patients, our group has narrowed down a BD-causative gene to 46 kb between the MICA and HLA-B genes by means of fine mapping analysis with eight microsatellite markers distributed within a 1100 kb segment around the HLA-B gene. To know whether this mapping result is generally observed in BD of another population we have investigated repeat polymorphisms of the same microsatellite markers in Jordanian BD patients. Furthermore, we have evaluated these data by Mantel-Haenzel stratified analysis to find out a primarily associated locus for BD. As a result, HLA-B51 was found to be the most strongly and primarily associated marker. This result suggests that the pathogenic gene of BD is HLA-B51 itself, but unlikely to be other genes located in the vicinity of HLA-B.     

Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development.

Notch signaling regulates cell fate determination in various tissues. We have reported the generation of mice with a pancreas-specific knockout of Rbp-j using Pdx.cre mice. Those mice exhibited premature endocrine and ductal differentiation. We now generated mice in which the Rbp-j gene was inactivated in Ptf1a-expressing cells using Ptf1a.cre mice. The timing of the Cre-mediated deletion in Rbp-j(f/f) Ptf1a.cre mice is 1 day later than that in Rbp-j(f/f) Pdx.cre mice. In Rbp-j(f/f) Ptf1a.cre mouse pancreases, at E13.5, the reduced Hes1 expression was accompanied by reduced epithelial growth, but premature endocrine cell differentiation was minimal. At E15.5, Pdx1 expression was repressed and acinar cell differentiation was reduced, but an increase in acinar cell proliferation was observed during the perinatal period. Our study indicates that, in addition to its role in preventing premature differentiation of early endocrine cells, Rbp-j regulates epithelial growth, Pdx1 expression, and acinar cell differentiation during mid-pancreatic development.     

Preparation of block copolyamides

Block copolyamides have been prepared by polymerization of amino- and carboxyl ended propolyamides of relatively low molecular weights. The structures of the block copolyamides were ascertained from the melting point vs. composition curves, the solubilities in methanol, and by dilatometry, in which two breaks, each corresponding to the melting temperature of one type of block segments, were observed. The amide interchange reaction, which disturbs the block regularity, is depressed at temperatures below 250°C. No practical differences in the thermal properties were observed between the two block polymers prepared by prepolyamide polymerization and by amide interchange of homopolyamides.     

Contribution of Fas ligand to cardiac allograft rejection

Effector mechanisms for allograft injury remain unclear. Inthe present study, we verified the contribution of Fas and Fasligand (FasL) to cardiac allograft rejection by utilizing theFas-deficlent lpr or FasL-deficient gid mice as the donor orrecipient. Cardiac myocytes prepared from normal mice, but notthose from lpr mice, constitutively expressed Fas and were susceptibleto FasL-mediated lysis. Survival of cardiac allografts was substantiallyprolonged when gld or lpr mice were used as the recipient. Incontrast, cardiac allografts from ipr mice were normally rejectedwithout a delay. Histological examination of the grafts in thegld or lpr recipients demonstrated a lesser cellular infiltrationand much milder myocyte damage. Proliferative response and cytotoxicT lymphocyte induction against the donor-type alloantigens werenot impaired in the gld or lpr recipients. These results indicatea substaintial contribution of FasL to cardiac allograft rejection,independent of Fas in the grafts. This raises a possibilitythat FasL may be more generally involved in tissue damage associatedwith various diseases than expected from the expression of Fasin the target organs.     

Sequencing-based typing of HLA-B*51 alleles and the significant association of HLA-B*5101 and -B*5108 with Behçet's disease in Greek patients

Beh?et's disease (BD) is widely known to be strongly associated with human leukocyte antigen (HLA) B51 in many different ethnic groups.Recently, HLA-B51 allele typing of Greek BD patients was performed to study the distribution of B*5101-B*5107 alleles in this Greek population, the B51 antigen strongly associated with BD was found to be predominantly encoded by allele B*5101. As it is now known that the B51 antigen can be encoded by 21 alleles, B*5101-B*5121, we performed HLA-B*51 allele genotyping among 58 Greek patients with BD. After serological HLA typing, typing of HLA-B*51 alleles was performed using the polymerase chain reaction-sequencing-based typing (PCR-SBT) method. The frequency of the B51 antigen was found to be significantly higher in the patient group as compared with the control group (75.9% of patients vs 22.0% of controls. In the genotyping of B51 alleles, 34 out of 44 B51-positive patients possessed B*5101, 13 out of the 44 carried B*5108. In contrast, all of the 9 B51-positive normal controls carried B*5101. This study revealed a strong association between Greeks with BD, both B*5101, B*5108, provided important insights into the molecular mechanism underlying the association between HLA status, this disease.     

Clinical Implications of Pre- and Postoperative Circulating Tumor DNA in Patients with Resected Pancreatic Ductal Adenocarcinoma

Annals of Surgical Oncology - The clinical implications of pre- and postoperative KRAS-mutated circulating tumor DNA (ctDNA) present in patients with pancreatic ductal adenocarcinoma (PDAC) have...     

TUBB3 is associated with PTEN,neuroendocrine differentiation,and castration resistance in prostate cancer

BackgroundTubulin-β3 encoded by the Tubulin-β3 (TUBB3) gene is a microtubule protein. Previous studies have shown that TUBB3 expression is upregulated in castration-resistant prostate cancer (CaP) and is involved in taxane resistance. However, the biological mechanism of TUBB3 involvement in the progression to castration-resistant CaP is not fully elucidated. This study aimed to analyze the expression and function of TUBB3 in localized and metastatic CaP.MethodsTUBB3 expression was determined using immunohistochemistry in localized and metastatic CaP. We also investigated the association between TUBB3, phosphatase and tensin homolog (PTEN), and neuroendocrine differentiation and examined the involvement of TUBB3 in new antiandrogen drugs (enzalutamide and apalutamide) resistance in metastatic CaP.ResultsIn 155 cases of localized CaP, immunohistochemistry showed that 5 (3.2%) of the CaP cases were positive for tubulin-β3. Kaplan–Meier analysis showed that high expression of tubulin-β3 was associated with poor prostate-specific antigen recurrence-free survival after radical prostatectomy. In 57 cases of metastatic CaP, immunohistochemistry showed that 14 (25%) cases were positive for tubulin-β3. Tubulin-β3 expression was higher in metastatic CaP than in localized CaP. High tubulin-β3 expression was correlated with negative PTEN expression. TUBB3 expression was increased in neuroendocrine CaP based on several public databases. PTEN knockout decreased the sensitivity to enzalutamide and apalutamide in 22Rv-1 cells. TUBB3 knockdown reversed the sensitivity to enzalutamide and apalutamide in PTEN-CRISPR 22Rv-1 cells. High expression of tubulin-β3 and negative expression of PTEN were significantly associated with poor overall survival in metastatic CaP treated with androgen deprivation therapy.ConclusionsThese results suggest that TUBB3 may be a useful predictive biomarker for survival and play an essential role in antiandrogen resistance in CaP.     

Efficacy of polyglycolic acid sheets and fibrin glue for prevention of bleeding after gastric endoscopic submucosal dissection in patients under continued antithrombotic agents

Background

A novel method for the prevention of bleeding after gastric endoscopic submucosal dissection (ESD) is necessary, as the numbers of patients taking antithrombotic agents have increased. This study aimed to assess the efficacy and safety of the covering method using polyglycolic acid (PGA) sheets and fibrin glue for ESD-induced ulcer in preventing post-ESD bleeding in patients under continued antithrombotic agents.

Methods

One hundred five consecutive gastric tumors among 84 patients who were treated by ESD under continued antithrombotic agents between April 2014 and September 2015 were enrolled in this study. The patients were classified into two groups, the covering group (52 lesions among 38 patients; those with ESD in whom PGA sheets and fibrin glue were used as the covering method) and the control group (53 lesions among 46 patients; ESD only), and their post-ESD bleeding rates were compared.

Results

No significant differences were seen in the number and type of antithrombotic agents, lesion location, median procedure time, and median resected specimen size between the groups. ESD was completed in all cases, with no cases of uncontrollable bleeding during the procedure. Post-ESD bleeding occurred in 5.8% (3/52) and 20.8% (11/53) in the covering and control groups, respectively. The post-ESD bleeding rate significantly differed between the groups (P = 0.04; odds ratio, 0.23; 95% confidential interval, 0.06–0.89). No adverse events were associated with the use of PGA sheets and fibrin glue.

Conclusions

The covering method using PGA sheets and fibrin glue has the potential to reduce post-ESD bleeding in patients receiving continued antithrombotic agents.

     

D-dimer predicts postoperative recurrence and prognosis in patients with liver metastasis of colorectal cancer

Background

Colorectal cancer is common, and its incidence is increasing throughout the world. The liver is a major metastatic site, and colorectal liver metastasis (CRLM) has a poor prognosis. Although liver resection is the most effective therapy for CRLM, postoperative recurrence is common. Thus, prognostic markers for CRLM are greatly needed. D-dimer, a fibrin cleavage product, has been shown to be related to colorectal tumor progression, and is also associated with malignant progression and recurrence in various cancers. Therefore, we evaluated the value of D-dimer in predicting the prognosis in CRLM.

Methods

We retrospectively evaluated 90 cases of resected CRLM to determine the correlation between D-dimer and patient survival. The cut-off value for D-dimer levels was determined using receiver operating characteristic curve analysis.

Results

Significant differences occurred in the recurrence group with higher D-dimer levels (P?=?0.00736*), while the optimal cut-off value was 0.6 µg/mL. High D-dimer levels (≥?0.6 µg/mL) were associated with poor recurrence-free survival (RFS; P?=?0.0000841*) and cancer-specific survival (CSS; P?=?0.00615*). In the multivariate analysis, D-dimer correlated with CRLM prognosis and independently predicted RFS (P?=?0.0179*).

Conclusion

High D-dimer levels were associated with poor RFS and CSS. D-dimer was an independent prognostic factor of RFS. Therefore, D-dimer may help predict recurrence and prognosis in patients with CRLM.