The importance of serum biglycan levels as a fibrosis marker in patients with chronic hepatitis B

WOS: 000411716300040PubMed ID: 27925300BackgroundLiver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the potential risks of liver biopsy, many studies related to non-invasive biomarkers of hepatic fibrosis have been performed. We aimed to assess the diagnostic value of serum biglycan as a non-invasive fibrosis marker in chronic hepatitis B patients. MethodsThis study included 120 patients with biopsy-proven hepatitis B patients and 60 healthy controls. Fibrosis stage and necroinflammatory activity were assessed in liver biopsy specimens. Biglycan level was measured using an ELISA assay. ResultsSerum biglycan levels of chronic hepatitis B patients were found to be significantly higher than those of healthy controls (337.3363.0pg/mL vs 189.1 +/- 61.9pg/mL, respectively, P<.001). There was a statistically significant positive correlation between serum biglycan level and fibrosis stage (P=.004; r=.213). Besides, a statistically significant positive correlation was found between serum biglycan level and necroinflammatory activity (P<.001; r=.271). The AUROC of BGN levels was 0.702 for fibrosis stage, differentiating patients from healthy controls with statistical significance (P<.001). The AUROC of BGN levels was 0.632 for necroinflammatory activity score, differentiating patients from healthy controls with statistical significance (P=.004). ConclusionsSerum biglycan might be used as a non-invasive marker of liver fibrosis. Further studies are needed to evaluate the usefulness of this marker

Cucurbitacin B and cisplatin induce the cell death pathways in MB49 mouse bladder cancer model

WOS: 000524425600001PubMed: 32252554Cisplatin-based chemotherapy is the standard regimen for bladder cancer patients, but its effectiveness is limited by high toxicity and the development of drug resistance. It has been reported in many studies that Cucurbitacin B has anti-carcinogenic effects by stimulating apoptosis and autophagy. Here we explored the potential role of cucurbitacin B on MB49 bladder syngeneic mouse tumor model. Single and combined doses of cucurbitacin B and cisplatin were applied to MB49 cell line and the cell viability was determined by Water-Soluble Tetrazolium Salt-1 (WST) method. After developing the tumor model, mice were randomly divided into four groups and then cucurbitacin B and cisplatin applied in the specified doses and time. The expression levels of apoptosis (Bcl-2, Bax, Caspase-3, cleaved Caspase-3) and autophagy proteins (Beclin-1 and LC3I, LC3II) were detected by Western Blot. Phospho-protein array analysis was performed to determine the relative levels of phosphorylation of proteins which are associated with the PI3K-Akt signaling pathway. Tumor tissues were analyzed by hematoxylin-eosin staining. In the present study, the results showed that cucurbitacin B inhibited the expression of Bcl-2 and increased the expression of Bax and cleaved Caspase 3. LC3II is markedly up-regulated in cucurbitacin B-treated cells. Cucurbitacin B reduced the phosphorylation of p27, PRAS40, and Raf-1 proteins. CuB + Cis combination synergistically decreased phosphorylation of AKT, ERK1/ERK2, mTOR, BAD levels and increased the level of AMPK alpha. PI3K/AKT/ mTOR pathway might be one of the targets of cucurbitacin B in MB49 bladder cancer mouse model. CuB + Cis combination reduced the tumor growth. Cucurbitacin B has no toxic effects on lung, liver, kidney, heart, and bladder. Indeed, cucurbitacin B can inhibit the tumor proliferation; induce caspase-dependent/-independent apoptosis and autophagy. Our study provided a novel perspective to research the effects of cucurbitacin B on the apoptotic and autophagic pathways in bladder cancer and a new target class for drug development. Impact statement Alternative agents that will increase the effectiveness of cisplatin, which are widely used in the advanced stage and metastatic bladder cancer, are being investigated. In previous studies, Cucurbitacin B (CuB), which is a natural compound from the Cucurbitaceae family has been shown to inhibit the proliferation of tumor cells and create synergistic effects with cisplatin. In this study, we investigated the synergistic effect of CuB with cisplatin for the first time in bladder cancer in vitro and in vivo models. Our findings showed that CuB treatment with cisplatin reduced cell proliferation, and reduced tumor development through activating apoptosis and autophagy via PI3K/AKT/mTOR signaling pathway. Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.Gazi University Research FundGazi University [01/201828]; Faculty Member Training Program (OYP) of the Council of Higher Education of Turkey (YOK)This study was conducted with financial support from the Gazi University Research Fund [the project code number 01/201828]; and by the Faculty Member Training Program (OYP) of the Council of Higher Education of Turkey (YOK)

The contribution of additional sampling in cholecystectomy materials: A multicenter prospective study

Objective: Cholecystectomy materials arc frequently encountered in routine practice. The aim of this study was to determine the true frequency of gallbladder lesions, the diagnostic consistency, and standardization of reports after macroscopic sampling and microscopic evaluation based on previously defined criteria.Material and Method: 14 institutions participated in the study within the Hepato-Pancreato-Biliary Pathology Study Group. Routinely examined cholecystectomies within the last year were included in the study in these institutions. Additional sampling was performed according to the indications and criteria. The number of blocks and samples taken in the first macroscopic examination and the number of blocks and samples taken in the additional sampling were determined and the rate of diagnostic contribution of the additional examination was determined.Results: A total of 5,244 cholecystectomy materials from 14 institutions were included in the study. Additional sampling was found to be necessary in 576 cases (10.98%) from all institutions. In the first macroscopic sampling, the mean of the numbers of samples was approximately 4 and the number of blocks was 2. The mean of the numbers of additional samples and blocks was approximately 8 and 4, respectively. The diagnosis was changed in 144 of the 576 new sampled cases while the remaining 432 stayed unaltered.Conclusion: In this study, it was observed that new sampling after the first microscopic examination of cholecystectomy materials contributed to the diagnosis. It was also shown that the necessity of having standard criteria for macroscopic and microscopic examination plays an important role in making the correct diagnosis