Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial

Background/Aims@#We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). @*Methods@#An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. @*Results@#DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. @*Conclusions@#The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

MicroRNA-374a Expression as a Prognostic Biomarker in Lung Adenocarcinoma

BACKGROUND: Lung cancer is the most common cause of cancer-related death, and adenocarcinoma is the most common histologic subtype. MicroRNA is a small non-coding RNA that inhibits multiple target gene expression at the post-transcriptional level and is commonly dysregulated in malignant tumors. The purpose of this study was to analyze the expression of microRNA-374a (miR-374a) in lung adenocarcinoma and correlate its expression with various clinicopathological characteristics.METHODS: The expression level of miR-374a was measured in 111 formalin-fixed paraffin-embedded lung adenocarcinoma tissues using reverse transcription-quantitative polymerase chain reaction assays. The correlation between miR-374a expression and clinicopathological parameters, including clinical outcome, was further analyzed.RESULTS: High miR-374 expression was correlated with advanced pT category (chi-square test, p=.004) and pleural invasion (chi-square test, p=.034). Survival analysis revealed that patients with high miR-374a expression had significantly shorter disease-free survival relative to those with low miR-374a expression (log-rank test, p=.032).CONCLUSIONS: miR-374a expression may serve as a potential prognostic biomarker for predicting recurrence in early stage lung adenocarcinoma after curative surgery.

Intraoperative continuous noninvasive hemoglobin monitoring in patients with placenta previa undergoing cesarean section: a prospective observational study

BACKGROUND: Obstetric patients with placenta previa are at risk for sever peripartum hemorrhage. Early detection of anemia and proper transfusion strategy are important for the management of obstetric hemorrhage. In this study, we assessed the utility and accuracy of noninvasive hemoglobin (SpHb) monitoring in patients with placenta previa during cesarean section.METHODS: Parturients diagnosed with placenta previa and scheduled for cesarean section under spinal anesthesia were enrolled. SpHb and laboratory Hb (Lab-Hb) were measured during surgery as primary outcomes.RESULTS: Seventy-four pairs of SpHb and Lab-Hb were collected from 39 patients. The correlation coefficient was 0.877 between SpHb and Lab-Hb (P < 0.001). The Bland-Altman plot showed a mean difference ± SD of 0.3 ± 0.8 g/dl between noninvasive Hb and Lab-Hb, and the limits of agreement were −1.2 to 1.8 g/dl. The magnitude of the difference between SpHb and Lab-Hb was < 0.5 g/dl in 64.9%; however, it was > 1.5 g/dl in 10.8%.CONCLUSIONS: SpHb monitoring had a good correlation with Lab-Hb. A small mean difference between SpHb and lab-Hb might not be clinically significant; however, the limits of agreements were not narrow. In particular, SpHb could be overestimated in the anemic population. Based on our results, further studies investigating the accuracy and precision of SpHb monitoring should be performed in parturients presenting Hb below 10 g/dl.

Clinicopathologic Correlations of E-cadherin and Prrx-1 Expression Loss in Hepatocellular Carcinoma

BACKGROUND: Developing predictive markers for hepatocellular carcinoma (HCC) is important, because many patients experience recurrence and metastasis. Epithelial to mesenchymal transition (EMT) is a developmental process that plays an important role during embryogenesis and also during cancer metastasis. Paired-related homeobox protein 1 (Prrx-1) is an EMT inducer that has recently been introduced, and its prognostic significance in HCC is largely unknown. METHODS: Tissue microarray was constructed using surgically resected primary HCCs from 244 cases. Immunohistochemical staining of E-cadherin and Prrx-1 was performed. The correlation between E-cadherin loss and Prrx-1 expression, as well as other clinicopathologic factors, was evaluated. RESULTS: E-cadherin expression was decreased in 96 cases (39.4%). Loss of E-cadherin correlated with a higher recurrence rate (p 40%) were independent prognostic factors for shorter overall survival. CONCLUSIONS: Prrx-1 was expressed in small portions of HCCs but not in normal livers. Additional studies with a large number of Prrx-1-positive cases are required to confirm the results of this study.

Clinicopathological Significance of Dual-Specificity Protein Phosphatase 4 Expression in Invasive Ductal Carcinoma of the Breast / 한국유방암학회지

PURPOSE: Dual-specificity protein phosphatase 4 (DUSP4), also known as mitogen-activated protein kinase phosphatase (MKP) 2 is a member of the inducible nuclear MKP group. The role of DUSP4 in cancer development and progression appears to vary with the type of malignancy. The purpose of this study was to investigate DUSP4 expression in a case series of invasive ductal carcinoma of the breast. METHODS: We constructed tissue microarrays consisting of 16, 14, 47, and 266 cases of normal breast tissue, usual ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma, respectively. DUSP4 expression was investigated by immunohistochemistry. RESULTS: Cytoplasmic DUSP4 expression was observed. DUSP4 was more frequently expressed in malignant than in benign cases (p=0.024). The mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (p=0.019). DUSP4 expression was significantly correlated with a larger tumor size (>2 cm, p=0.015). There was no significant correlation between overall survival or disease-free survival and DUSP4 expression in all 266 patients. We evaluated the impact of DUSP4 expression on the survival of 120 patients with T1-stage tumors. Interestingly, Kaplan-Meier survival curves revealed that DUSP4 expression had a significant effect on both overall patient survival (p=0.034, log-rank test) and disease-free survival (p=0.045, log-rank test). In early T-stage breast cancer, DUSP4 expression was associated with a worse prognosis. CONCLUSION: DUSP4 is frequently upregulated in breast malignancy, and may play an important role in cancer development and progression. In addition, it may be a marker of adverse prognosis, especially in patients with early T1-stage cancer.

High MicroRNA-370 Expression Correlates with Tumor Progression and Poor Prognosis in Breast Cancer / 한국유방암학회지

PURPOSE: Deregulation of microRNA-370 (miR-370) has been reported in various cancers, in which it can act as either an oncogene or a tumor suppressor gene. However, the clinicopathologic significance of miR-370 expression in breast cancer has not been studied. METHODS: The expression of miR-370 was determined with quantitative real-time polymerase chain reaction in 60 formalin-fixed, paraffin-embedded primary breast cancer tissues. Additionally, the protein expression levels of previously known targets of miR-370, such as FOXM1, FOXO1, and FOXO3a, were detected using immunohistochemistry. Finally, we analyzed its correlation with target protein expression, clinicopathologic features, and clinical outcome. RESULTS: High levels of miR-370 expression correlated with lymph node metastasis (p=0.009), advanced stage (p=0.002), and frequent perineural invasion (p=0.042). Moreover, patients with high miR-370 expression had poor disease-free survival compared with the low-expression group. However, no correlation was observed between miR-370 and its target protein expression. CONCLUSION: Our results indicate that upregulation of miR-370 in breast cancer is correlated with breast cancer progression and that it might be a potential biomarker for predicting clinical outcomes.

Lymphoepithelioma-like Carcinoma of the Renal Pelvis: A Case Report and Review of the Literature

No abstract available.

Self-pulsed Washable Seton during a Modified Hanley Operation for a Deep Horseshoe Fistula

PURPOSE: The modified Hanley technique, which is used for treatment of a deep horseshoe fistula, has reduced damage to the external anal sphincter compared to the classic Hanley technique, but its shortcoming is that it causes inconvenience to the patient due to the fact that a drainage tube must be left in place for a long time. To solve this problem, the authors devised a self-pulsed washable seton and then compared the results of its use to determine its clinical usefulness. METHODS: The subjects of this study were 34 patients who were diagnosed with a deep posterior complex anal fistula and who were operated on by using the modified Hanley technique between January 1999 and December 2004. Twelve patients who were treated with the self-pulsed washable seton were classified as Group A, and 12 patients who were treated by using a conventional loose seton were placed in Group B. These two groups were compared for period of purulent discharge, period of leaving the seton alone, and recurrence rate. RESULTS: The period of purulent discharge was 18.75 days (15~24) for group Aand 29.75 days (24~37) for group B. The period of leaving the seton was 21.58 days (18~29) for group A and 32.58 days (28~39) for group B. The recurrence rate after surgery was 8.3% in group A and 16.7% in group B. CONCLUSIONS: The self-pulsed washable seton devised by the authors shortened the treatment period through more effective wound management, so we propose using it as a new method for treating a deep posterior horseshoe fistula.