A computed tomography-based comprehensive standardized adrenal tumor scoring model for predicting the perioperative outcomes of retroperitoneal laparoscopic adrenal surgery.

Background: Many imaging scoring models have been developed for tumor surgery to provide critical guidance for the selection of surgical methods. However, little research has been aimed at developing scoring models for adrenal tumors and retroperitoneal laparoscopic adrenal surgery (RLAS), which has become the primary technique for treating adrenal tumors. The study set out to establish a computed tomography (CT)-based adrenal tumor scoring model for predicting perioperative outcomes in patients with adrenal tumors who have undergone RLAS. Methods: The retrospective analysis included 306 patients with adrenal tumors diagnosed by preoperative unenhanced or enhanced CT from January 2014 to August 2018 in the First Affiliated Hospital of Fujian Medical University. CT images were used to quantify the tumor location and size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the adhesion of periadrenal fat (PF); and the tumor CT enhancement value. We conducted multivariate ordinal logistic regression analysis to screen variables and performed principal component analysis to construct a novel scoring model for RLAS. The perioperative outcomes of RLAS were evaluated according to postoperative length of stay, operative time (OT), intraoperative blood loss (IBL), and postoperative complications. Results: The final scoring model included tumor size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the tumor CT enhancement value; the adhesion of the PF; and the functional status of adrenal tumors. The total score had positive correlations with the OT (rs=0.431), IBL (rs=0.446), and postoperative length (rs=0.180) (all P values <0.001). Compared to any single metric, the total score provided better prediction of OT and IBL. The grading system for RLAS based on the scoring model also performed well in predicting the complexity and difficulty of RLAS. The coincidence rate for these factors was good (all P values <0.001). Conclusions: The developed model is feasible and repeatable in the prediction of the perioperative outcomes, complexity, and difficulty of RLAS.

HMGB1/RAGE axis mediates the apoptosis, invasion, autophagy, and angiogenesis of the renal cell carcinoma.

BACKGROUND: High mobility group box 1 protein (HMGB1) is a sort of non-histone protein in chromatin, which plays an important role in tumor proliferation, invasion, and immune escape. HMGB1-RAGE (receptor for advanced glycation end products) interactions have been reported to be important in a number of cancers. METHODS: CCK8, flow cytometry and qRT-PCR were used to detected cell viability, apoptosis and gene expression, respectively. RESULTS: In the present study, we demonstrated that HMGB1/RAGE axis regulated the cell proliferation, apoptosis, and invasion of the renal cell carcinoma (RCC). Further, we discovered that HMGB1/RAGE axis increased the expression of autophagic proteins LC3 and Beclin-1 in RCC. Finally, we used a coculture model of human umbilical vein endothelial cells with RCC cell lines to find out that HMGB1 also increased the expression of VEGF and VEGFR2 in human umbilical vein endothelial cells. An in vivo study further confirmed that HMGB1 knockdown inhibited RCC tumor growth. CONCLUSION: Our results illustrated that HMGB1/RAGE axis mediated RCC cell viability, apoptosis, invasion, autophagy, and angiogenesis, which provides a novel theoretical basis for using HMGB1 as the target in RCC.

Neoalbaconol inhibits cell growth of human cholangiocarcinoma cells by up-regulating PTEN.

The recently isolated small-molecule neoalbaconol (NA) from Albatrellus confluens has been suggested to possess the ability to inhibit cell growth of many cancer cells. In this study, we investigated the role of NA in the regulation of cell apoptosis in human cholangiocarcinoma cell lines both in vitro and in vivo. Our results indicate that NA could induce cancer cell death via the AKT pathway by targeting phosphorate and tension homolog detected on chromosome 10 (PTEN) and supported the feasibility of NA being a novel chemotherapeutic treatment for human cholangiocarcinoma.

Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma.

The receptor for advanced glycation end products (RAGE) is involved in a variety of biological processes, including tumorigenisis. Previous studies have demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule - vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were used to explore the RAGE and VEGFR-2 gene expression levels and the protein of VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi-quantification of endothelial cell marker CD34 combined with caldesmon, which was detected by microvessel density (MVD) technique and immunohistochemistry. Tumors were classified as low or high RAGE-expressing using the median as the cut-off. Immunofluorescence staining for RAGE protein was performed as well. Additionally, the median gene expression levels of VEGFR-2 in the tumors were significantly lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28-0.39) compared to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29-0.61), (P=0.03). The median MVD was significantly lower in the tumors expressing low levels of RAGE, 6.5 (95% CI, 6.21-7.43), compared to the expressing high levels, 7.9 (95% CI, 6.25-8.93), (P<0.01). Further, a positive association was certified with VEGFR-2 protein levels, P=0.07. Besides, RCC with high levels of RAGE expression are associated with high VEGFR-2 mRNA/protein levels and a higher density of microvessels; conversely, Kaplan-Meier survival analysis suggests that a significant correlation of elevated RAGE expression with decreased overall survival and metastasis-free survival. Our results establish that RAGE was identified as a potential prognostic biomarker for disease prognosis of RCC.

Long non-coding RNAs and hepatocellular carcinoma.

Recent advances in next-generation sequencing technology in transcriptome analysis have helped identify numerous non-coding RNAs. The long non-coding RNA (lncRNA) is commonly defined as an RNA molecule with a length of 200 bp-100 kbp that lacks protein-coding potential. LncRNAs play a critical role in the regulation of gene expression, including chromatin modification, transcription and post-transcriptional processing. It has been confirmed that dysregulation of lncRNAs is associated with a number of human diseases, particularly tumors. In this study, we focused on the most extensively investigated lncRNAs in hepatocellular carcinoma (HCC). The biological functions and molecular mechanisms of the majority of lncRNAs have yet to be investigated. The improved knowledge on lncRNAs in HCC may help identify lncRNAs that may be used as novel prognostic markers and therapeutic targets.

miR-340 reverses cisplatin resistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway.

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/ CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR- 340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/ CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

[Expression of miRNA-29b and its clinical significances in primary hepatic carcinoma].

OBJECTIVE: To explore the clinical value of miRNA-29b expression and the combined detection of serum miRNA-29b and alpha-fetoprotein (AFP) in the diagnosis of primary hepatic carcinoma(PHC). METHODS: From January 2007 to May 2010, the serum levels of miRNA-29b and AFP from 96 healthy controls and 87 PHC patients were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) respectively. The relationship of miRNA-29b and various clinical parameters was analyzed. RESULTS: Serum levels of miRNA-29b in PHC pre-operative group (0.250 (0.124 - 0.381)) significantly decreased versus the control group [0.860 (0.587 - 1.338)] and the post-operative group (0.890 (0.637 - 1.414)) (P < 0.001). Also, the levels of AFP in PHC pre-operative group (65.4 (20.1 - 212.3)) was obviously higher than that in the control group (13.3 (7.1 - 19.8)) and the post-operative group (23.2 (11.6 - 55.7)) (P < 0.001). A lower expression of miRNA-29b was correlated with lower differentiation and higher TNM stages (P < 0.045, P < 0.001). Kaplan-Meier curve analysis revealed that PHC patients with a low serum expression of miRNA-29b had a significantly shortened overall survival when compared with a high serum expression of miRNA-29b (25.52 vs 36.94 months, P = 0.008). Multivariable Cox regression analysis indicated that the serum expression of miRNA-29b was an independent risk factor for overall survival. Relative risk was 0.482 (95% confidence interval: 0.236 - 0.985). The critical values for miRNA-29b and AFP were determined at 0.38 and 23.1 µg/L through the ROC curves. Under the critical value, the sensitivity of miRNA-29b and AFP were 75.9% and 70.1% and the specificity of miRNA-29b and AFP 89.5% and 92.7% respectively. Combined detection could increase the sensitivity up to 87.3%, and achieve a specificity of 88.5%. CONCLUSION: The combined detection of miRNA-29b and AFP aids the diagnosis of PHC and the prediction of its prognosis.

[Distribution and significance of α1-adrenoceptor subtypes in patients with chronic prostatitis in prostate, bladder detrusor and posterior urethral tissue].

OBJECTIVE: To study the distribution of alpha1-adrenoceptor (α1-AR) subtype in prostate, posterior urethra and bladder detrusor of patients with chronic prostatitis (CP). METHODS: The prostate specimens were collected at autopsy from 30 organ donors (aged 20-35 years old) dying of non-prostatic diseases. The pathological specimens of prostate peripheral zone were examined. The method of real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) was employed for quantification of α1a-AR and α1b-AR subtype expression in prostate transition zone and its surrounding zone, posterior urethra and bladder detrusor tissue. RESULTS: Among all donors, there were 24 cases with pathological inflammation in prostatic peripheral zone and 6 with pathological non-inflammation. The mRNA expression of α1-AR subtypes in bladder detrusor and posterior urethra was significantly higher in the inflammation group than in the control group (P<0.05). While the mRNA expression of α1-AR subtypes in the bladder detrusor and posterior urethra was significantly lower in the inflammation group than in the control group (P<0.05). CONCLUSION: An abnormal expression of α1-AR subtypes in bladder detrusor and posterior urethra may explain various urodynamic changes in CP and lead to the occurrence and development of CP in prostate, posterior urethra and bladder detrusor.

[Establishment and preliminary application of polymerase chain reaction with confronting two-pair primers for the single nucleotide polymorphisms of metabolic enzymes].

OBJECTIVE: To develop a simple, accurate, rapid, economic, large-scale detection method for the detection of single nucleotide polymorphisms (SNPs) metabolic enzymes, using polymerase chain reaction with confronting two-pair primers (PCR-CTPP). METHODS: The primers of CYP1A1 (A4889G), EPHX1 (A416G) and NQO1 (C609T) were designed for PCR-CTPP, and the PCR conditions were optimized. The results of genotyping were verified by DNA sequencing. The above SNPs were detected by the PCR-CTPP detection method in a randomly selected 183 healthy individuals of Han ethnicity. The genotype frequencies were analyzed and compared with people from other ethnicities. RESULTS: The allele-specific bands of CYP1A1 (A4889G), EPHX1 (A416G) and NQO1 (C609T) were successfully amplified by PCR-CTPP under the optimal conditions and the results of genotyping were consistent with DNA sequencing. Among 183 healthy Han individuals, the genotypic distributions of CYP1A1 (A4889G) , EPHX1 (A416G) and NQO1 (C609T) showed that the wild-type, homozygous variants, and heterozygotes were 103 (56.3%), 8 (4.4%), 72 (39.3%) and 142 (77.6%), 4 (2.2%), 37(20.2%), 60(32.8%), 32 (17.5%), 91 (49.7%) respectively. The distributions of genotypes were all in accordance with the Hardy-Weinberg equilibrium (P > 0.05), with statistical differences and with other ethnic populations (P < 0.05). CONCLUSION: The SNPs of metabolic enzymes can be detected by PCR-CTPP method which is simple, accurate, rapid, economic and with large scale. PCR-CTPP can be used for large scale clinical and epidemiological screening.