Insights into the Divergence of Chinese Ips Bark Beetles during Evolutionary Adaptation.

Many bark beetles of the genus Ips are economically important insect pests that cause severe damage to conifer forests worldwide. In this study, sequencing the mitochondrial genome and restriction site-associated DNA of Ips bark beetles helps us understand their phylogenetic relationships, biogeographic history, and evolution of ecological traits (e.g., pheromones and host plants). Our results show that the same topology in phylogenetic trees constructed in different ways (ML/MP/BI) and with different data (mtDNA/SNP) helps us to clarify the phylogenetic relationships between Chinese Ips bark beetle populations and Euramerican species and their higher order clades; Ips bark beetles are polyphyletic. The structure of the mitochondrial genome of Ips bark beetles is similar and conserved to some extent, especially in the sibling species Ips typographus and Ips nitidus. Genetic differences among Ips species are mainly related to their geographic distribution and different hosts. The evolutionary pattern of aggregation pheromones of Ips species reflects their adaptations to the environment and differences among hosts in their evolutionary process. The evolution of Ips species is closely related to the uplift of the Qinghai-Tibet Plateau and host switching. Our study addresses the evolutionary trend and phylogenetic relationships of Ips bark beetles in China, and also provides a new perspective on the evolution of bark beetles and their relationships with host plants and pheromones.

Effect of α2­macroglobulin in the early stage of jaw osteoradionecrosis.

Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2­macroglobulin (α2M) could prevent early­stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate­resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit­8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase­1 (HO­1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8­hydroxy­2'­deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase­1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early­stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.

Periodontitis and inflammatory bowel disease: a meta-analysis.

BACKGROUND: Periodontitis was reported to be associated with inflammatory bowel disease (IBD). However, the association between them has not been firmly established in the existing literature. Therefore, this meta-analysis was conducted to evaluate the relationship between periodontitis and IBD. METHODS: Electronic databases were searched for publications up to August 1, 2019 to include all eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated to determine the association between periodontal disease and IBD using a random or fixed effects model according to heterogeneity. RESULTS: Six eligible studies involving 599 IBD patients and 448 controls were included. The pooled OR between periodontitis and IBD was 3.17 (95% CI: 2.09-4.8) with no heterogeneity observed (I2 = 0.00%). The pooled ORs were 3.64 (95% CI: 2.33-5.67) and 5.37 (95% CI: 3.30-8.74) for the associations between periodontitis and the two sub-categories of IBD, Crohn' s disease and ulcerative colitis, respectively. CONCLUSIONS: The results demonstrated that periodontitis was significantly associated with IBD. However, the mechanisms underlying periodontitis and IBD development are undetermined. Further studies are needed to elucidate this relationship.

Immune-related gene signature for predicting the prognosis of head and neck squamous cell carcinoma.

BACKGROUND: Immune-related genes (IRGs) were linked to the prognosis of head and neck squamous cell carcinoma (HNSCC). This study aimed to identify the effects of an immune-related gene signature (IRGS) that can predict the of HNSCC prognosis. METHODS: The expression data of 770 HNSCC patients from the TCGA database and the GEO database were used. To explore a predictive model, the Cox proportional hazards model was applied. The Kaplan-Meier survival analysis, as well as univariate and multivariate analyses were performed to evaluate the independent predictive value of IRGS. To explore biological functions of IRGS, enrichment analyses and pathway annotation for differentially expressed genes (DEGs) in different immune groups were applied, as well as the immune infiltration. RESULTS: A prognostic signature comprising 27 IRGs was generated. IRGS significantly stratified HNSCC patients into high and low immune risk groups in regard to overall survival in the training cohort (HR = 3.69, 95% CI 2.73-4.98, P < 0.001). Likewise, IRGS could be linked to the prognosis of HNSCC in patients of the validation cohort (HR = 1.84, 95% CI 1.21-2.81, P < 0.01). Even after adjusting for TNM stage, IRGS was maintained as an independent predictor in the multivariate analysis (HR = 3.62, 95% CI 2.58-5.09, P < 0.001), and in the validation cohort (HR = 1.73, 95% CI 1.12-2.67, P = 0.014). The IFN-α response, the IFN-γ response, IL-2/STAT5 signaling, and IL-6/JAK/STAT3 signaling were all negatively correlated with the immune risk (P < 0.01). Immune infiltration of the high-risk group was significantly lower than that of the low-risk group (P < 0.01). Most notably, the infiltration of CD8 T cells, memory-activated CD4 T cells, and regulatory T cells was strongly upregulated in the low immune risk groups, while memory resting CD4 T cell infiltration was downregulated (P < 0.01). CONCLUSION: Our analysis provides a comprehensive prognosis of the immune microenvironments and outcomes for different individuals. Further studies are needed to evaluate the clinical application of this signature.

Protective role of α2-macroglobulin against jaw osteoradionecrosis in a preclinical rat model.

OBJECTIVE: We have previously demonstrated the effect of alpha-2-macroglobulin (α2M) in the remediation of radiation-induced cellular damage. Here, we investigated the protective effects of α2M in a preclinical rat model of jaw osteoradionecrosis (ORN). METHODS: Eighteen rats were divided randomly into three groups: the control group, the radiation therapy (RT) alone group, and the radiated mandibles pretreated with α2M (α2M + RT) group. One month after radiation, all left molar teeth were extracted. After another 3 months, the animals were sacrificed and body weight, histopathology, microcomputed tomography and immunofluorescence were evaluated in all groups. RESULTS: The RT group showed serious alopecia, bone exposure, inflammation, necrosis, fibrosis, and the absence of new bone formation within the socket. The α2M + RT group exhibited less alopecia than the RT group and slight inflammation and fibrosis in the bone marrow cavity. The cortical bone was similar to normal bone tissue. Interestingly, compared with RT group, serum superoxide dismutase levels in the α2M + RT group increased at the 1th day (P = 0.037), 14th day (P = 0.012), while reactive oxygen species levels clearly decreased at the 1th day (P< 0.001), 14th day (P = 0.007), and 28th day (P = 0.013). CONCLUSIONS: A clinically translational model of jaw ORN was successfully established and the application of α2M prior to radiation protected the bone from being injured by the radiation, possibly related to oxidative stress.

Effect of adjuvant hormone therapy in patients with prostate cancer: A meta-analysis of randomized controlled trials.

OBJECTIVES: To summarize the evidence regarding the treatment effect of adjuvant hormone therapy (AHT) in patients with prostate cancer (PCa). AHT following radiotherapy, chemotherapy, or surgery is widely used in patients with PCa. However, the treatment effect is inconsistent in individual trials. METHODS: The electronic databases including PubMed, EmBase, and Cochrane Library were searched to identify randomized controlled trials (RCTs) in September 2016. RCTs that evaluated the effects of AHT in patients with PCa were included. Hazard ratio (HR) and relative risks (RR) were used to measure the treatment effects of AHT using a random effects model. The analyses were further stratified by factors that could affect the treatment efficacy. RESULTS: A total of 14,594 potential studies were identified, and 27 RCTs were included. Compared with the control group, patients who received AHT were associated with a significant improvement in overall survival (OS) (HR: 0.78; 95% confidence interval [CI]: 0.71-0.85; P <.001), disease-free survival (DFS) (HR: 0.50; 95% CI: 0.39-0.65; P <.001), total mortality (RR: 0.90; 95% CI: 0.85-0.96; P = .001), recurrence (RR: 0.70; 95% CI: 0.60-0.81; P <.001), and disease-specific mortality (RR: 0.70; 95% CI: 0.56-0.87; P <.001). However, no significant difference was observed between AHT and control for response rate (RR: 1.75; 95% CI: 0.91-3.37; P = .095). CONCLUSIONS: The findings of this meta-analysis confirmed that patients who received AHT had a significant improvement in OS, DFS, total mortality, recurrence, and disease-specific mortality. Further, large-scale RCTs are required to evaluate the treatment effect in specific subpopulations.

Protective effects of α­2­macroglobulin on human bone marrow mesenchymal stem cells in radiation injury.

Osteoradionecrosis of the jaws (ORNJ) is a complication of oral and maxillofacial malignancy that arises following radiotherapy; progressive jaw necrosis severely decreases the quality of life of patients. Human bone marrow mesenchymal stem cells (hBMMSCs) are a cell type with self­renewal and pluripotent differentiation potential in the bone marrow stroma. These cells are associated with bone tissue regeneration and are one of the primary cell types affected by bone tissue radiation injury. α­2­macroglobulin (α2M) is a glycoprotein­rich macromolecule that interacts with cytokines, growth factors and hormones to serve a variety of biological roles. In addition, α2M possesses radio­protective effects. The aim of the present study was to investigate whether α2M has protective effects against radiation injury of hBMMSCs. Cell counting kit­8 and colony formation assays were used to monitor cell proliferation. Western blot analysis and reverse transcription­quantitative polymerase chain reaction were used to detect Beclin1, microtubule­associated protein 1A/1B, sex determining region Y, Nanog, runt­related transcription factor 2, osteoglycin and manganese superoxide dismutase expression. The formation of calcium nodules was evaluated by Alizarin red staining after osteogenic induction. Flow cytometric analysis of Annexin­V and propidium iodide double staining was used to detect changes in apoptosis rate. Alkaline phosphatase and superoxide dismutase activity were determined using colorimetric assays. Reactive oxygen species levels were detected using 2',7'­dichlorodihydrofluorescein diacetate. The results of the present study revealed that α2M increased the rate of proliferation, reduced autophagy, alleviated pluripotent differentiation injury, increased the osteogenic differentiation ability and decreased the rate of apoptosis in hBMMSCs following irradiation via an antioxidative pathway. In conclusion, α2M exhibited protective effects against radiation injury in hBMMSCs and may be considered a potential therapeutic agent for the prevention and treatment of ORNJ.

Laparoscopic versus open nephroureterectomy for upper urinary tract urothelial carcinoma: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of laparoscopic nephroureterectomy (LNU) and open nephroureterectomy (ONU) for the treatment of upper urinary tract urothelial carcinoma (UTUC). METHODS: PubMed, Embase, and Cochrane databases were selected for systematic review of trials that compared outcomes of LNU and ONU. Meta-analysis was performed using RevMan 5.3 and STATA 13.0 software. RESULTS: LNU was associated with longer operation time (P < .001), shorter hospital stay (P < .001), less blood loss (P = .006) and lower rate of transfusion (P < .001). The occurrence of complications, including minor (P = .52), major (P = .21) and total complications (P = .19) were similar between LNU and ONU. There was no significant difference in the rate of 5-year recurrence-free survival (P = .90), 5-year cancer-specific survival (P = .12), and 5-year overall survival (P = .11) as well as 2-year RFS (P = .84), 2-year CSS (P = .86), and 2-year OS (P = .25). CONCLUSION: Our results indicated that LNU is a safe and effective method to treat UTUC. Given the limitations of this study, further multicenter, randomized trials are required to confirm these findings.

miR-488 inhibits cell growth and metastasis in renal cell carcinoma by targeting HMGN5.

PURPOSE: microRNAs are thought to play crucial roles in tumorigenesis. Dysregulation of miR-488 has been implicated to be involved in several cancer progressions. However, the biological functions of miR-488 in renal cell carcinoma (RCC) remain unclear. This study aimed to explore the molecular mechanism underlying the role of miR-488 in RCC development. MATERIALS AND METHODS: The expression levels of miR-488 were detected in 38 paired RCC tumor samples and cell lines by quantitative real-time polymerase chain reaction method. miR-488 was upregulated by mimics transfection in RCC cell lines. MTT, colony formation, transwell assay, flow cytometry assay, and a xenograft model were performed to determine cell proliferation, invasion, migration, epithelial-to-mesenchymal transition, and apoptosis in vitro and in vivo. Moreover, the potential target of miR-488 was verified by dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and Western blot. The correlation between miR-488 expression and its target gene expression was confirmed by Spearman's correlation analysis in 38 selected RCC tissue samples. RESULTS: We found that miR-488 was remarkably downregulated in human RCC samples and cell lines compared with paired normal tissues and cell lines. Functional investigations revealed that overexpression of miR-488 significantly suppressed cell proliferation, invasion, and migration, and promoted cell apoptosis in RCC cells. Nucleosome binding protein 1 (high-mobility group nucleosome binding domain 5 [HMGN5]) was identified as a direct target of miR-488, and an inverse relationship was found between miR-488 expression and HMGN5 mRNA levels in RCC specimens. Rescue experiments suggested that restoration of HMGN5 partially abolished miR-488-mediated cell proliferation and invasion inhibition in RCC cells through regulating phosphatidylinositol 3-kinase/protein kinase B/the mammalian target of rapamycin and epithelial-to-mesenchymal transition signaling pathways. CONCLUSION: These data indicated that miR-488 acted as a tumor suppressor in RCC proliferation and invasion by targeting HMGN5, which might provide potential therapeutic biomarker for RCC patients.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Association of toll-like receptors with the risk of oral squamous cell carcinoma.

AIM OF STUDY: Association of toll-like receptors (TLRs) with the risk of oral squamous cell carcinoma (OSCC) from the published reports is still conflicting. This study was conducted to evaluate the relationship between TLRs and the risk of OSCC using meta-analysis method. MATERIALS AND METHODS: The association studies were identified from PubMed and Cochrane Library on April 01 2015, and eligible investigations were included and synthesized using meta-analysis method. RESULT: Three reports were recruited into this meta-analysis for the association of TLRs with OSCC susceptibility. In this meta-analysis, we found that TLRs were not associated with OSCC susceptibility. However, in the sub-group analysis, we found that TLR-7 was associated with OSCC risk. CONCLUSION: TLR-7 was associated with OSCC risk. TLR-7 might be an indicator to predict the OSCC risk. However, more studies should be conducted to confirm it.

MicroRNA-384 Inhibits the Growth and Invasion of Renal Cell Carcinoma Cells by Targeting Astrocyte Elevated Gene 1.

MicroRNAs (miRNAs) are emerging as pivotal regulators in the development and progression of various cancers, including renal cell carcinoma (RCC). MicroRNA-384 (miR-384) has been found to be an important cancer-related miRNA in several types of cancers. However, the role of miR-384 in RCC remains unclear. In this study, we aimed to investigate the potential function of miR-384 in regulating tumorigenesis in RCC. Here we found that miR-384 was significantly downregulated in RCC tissues and cell lines. Overexpression of miR-384 significantly inhibited the growth and invasion of RCC cells, whereas inhibition of miR-384 had the opposite effects. Bioinformatic analysis and luciferase reporter assay showed that miR-384 directly targeted the 3'-untranslated region of astrocyte elevated gene 1 (AEG-1). Further data showed that miR-384 could negatively regulate the expression of AEG-1 in RCC cells. Importantly, miR-384 expression was inversely correlated with AEG-1 expression in clinical RCC specimens. Moreover, miR-384 regulates the activation of Wnt signaling. Overexpression of AEG-1 significantly reversed the antitumor effects of miR-384. Overall, these findings suggest that miR-384 suppresses the growth and invasion of RCC cells via downregulation of AEG-1, providing a potential therapeutic target for the treatment of RCC.

MicroRNA­613 inhibits proliferation and invasion of renal cell carcinoma cells through targeting FZD7.

MicroRNAs (miRNAs) have emerged as critical regulators in cancer progression. miR­613 has been reported as a tumor suppressor gene in many types of human cancers. However, the function of miR­613 in renal cell carcinoma (RCC) remains unclear. In the present study, the authors aimed to detect the expression of miR­613 and its function in RCC cell lines. miR­613 was reported to be significantly downregulated RCC cell lines. Functional analyses demonstrated that overexpression of miR­613 significantly decreased RCC cell proliferation and invasion. Bioinformatics analysis showed that Frizzled7 (FZD7) was a predicted target of miR­613, which was verified by dual­luciferase reporter assay, reverse transcription quantitative­polymerase chain reaction and western blot analysis. Restoration of FZD7 significantly reversed the suppressive effects of miR­613 on RCC cell proliferation and invasion. Taken together, the results of the present study indicated that miR­613 functions as a tumor suppressor that inhibits RCC cell proliferation and invasion by targeting and inhibiting FZD7, providing novel insight into RCC pathogenesis and a potential therapeutic target for RCC.

Identification of a Novel UT-B Urea Transporter in Human Urothelial Cancer.

The urea transporter UT-B is widely expressed and has been studied in erythrocyte, kidney, brain and intestines. Interestingly, UT-B gene has been found more abundant in bladder than any other tissue. Recently, gene analyses demonstrate that SLC14A1 (UT-B) gene mutations are associated with bladder cancer, suggesting that urea transporter UT-B may play an important role in bladder carcinogenesis. In this study, we examined UT-B expression in bladder cancer with human primary bladder cancer tissues and cancer derived cell lines. Human UT-B has two isoforms. We found that normal bladder expresses long form of UT-B2 but was lost in 8 of 24 (33%) or significantly downregulated in 16 of 24 (67%) of primary bladder cancer patients. In contrast, the short form of UT-B1 lacking exon 3 was detected in 20 bladder cancer samples. Surprisingly, a 24-nt in-frame deletion in exon 4 in UT-B1 (UT-B1Δ24) was identified in 11 of 20 (55%) bladder tumors. This deletion caused a functional defect of UT-B1. Immunohistochemistry revealed that UT-B protein levels were significantly decreased in bladder cancers. Western blot analysis showed a weak UT-B band of 40 kDa in some tumors, consistent with UT-B1 gene expression detected by RT-PCR. Interestingly, bladder cancer associate UT-B1Δ24 was barely sialylated, reflecting impaired glycosylation of UT-B1 in bladder tumors. In conclusion, SLC14A1 gene and UT-B protein expression are significantly changed in bladder cancers. The aberrant UT-B expression may promote bladder cancer development or facilitate carcinogenesis induced by other carcinogens.

Prognostic analysis of Chinese patients with metastasis renal cell cancer receiving sorafenib: results from a multicenter long-term follow-up retrospective study.

The effects of sorafenib for Chinese patients with metastatic renal cell cancer (mRCC) were evaluated to figure out the relationship between clinical variables and prognosis. The data were analyzed retrospectively from six comprehensive cancer centers in Northeast China. All cases were diagnosed as mRCC histopathologically without exception. Patients were taken 400 mg sorafenib orally twice daily until progression of disease or intolerable toxic reaction occurred. Overall survival (OS), progression-free survival (PFS), and the influence of clinical variables on survival were appointed as main outcome measures. Clinical data were analyzed using SPSS statistical software. P<0.05 was considered as statistically significant. A total of 131 patients were available for survival analysis. The median follow-up periods were 16.9 months, and the median OS and PFS were 16.1 months and 10.5 months, respectively. Univariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, and previous therapy were significantly associated with OS, whereas PFS was merely associated with ECOG PS and previous therapy. The multivariate analysis suggested that ECOG PS, metastatic sites, and previous therapy were the independent prognostic factors for OS, and ECOG PS and previous therapy as the independent prognostic factors for PFS. In the subgroup analysis for patients with visceral metastasis, the prognosis of patients with lung metastasis alone was better than those cases with liver metastasis alone or multiple organs metastasis. In our study, sorafenib shows a higher curative activity for patients with mRCC in Northeast China. ECOG PS, metastatic lesions, and previous therapy may be important parameters for OS and PFS prediction. Lung metastases alone may be a more sensitive indicator for sorafenib than other organ metastases.

Soluble Expression of Bladder Cancer Biomarker Matrix Metalloproteinase 1.

BACKGROUND: Matrix metalloproteinase 1 (MMP1) has been shown as a novel unique biomarker of bladder cancer in urine. MMP1 can only be detected using conventional and time-consuming methods, such as ELISA and Western. Refolded MMP1 has been achieved and used in probe screen for many years, while there is no clinical application for MMP1 detection until now. Soluble expression of MMP1 is necessary in urine detection. METHODS: cDNA of MMP1 has been isolated from human embryonic kidney 293(HEK293) cells. The catalytic domain of MMP1 is expressed as fusion protein with Escherichia coli thioredoxin (TrxA). The 30 kDa recombinant proteins were purified by Ni-chelating chromatography. The activity of soluble MMP1 was determined and compared with refolded MMP1 by zymography. RESULTS: Compared with refolded MMP1, TrxA can increase the solubility of MMP1. The soluble MMP1 has the same protein sequences with refolded MMP1 and increased 1.54-fold of gelatin-degradation activities than refolded MMP1. CONCLUSION: Successfully soluble expression of MMP1 has been achieved by fusion expression and will make progress in discovering specific molecular probes against MMP1.

Beneficial effect of T follicular helper cells on antibody class switching of B cells in prostate cancer.

Prostate cancer is the most common malignancy in males and easily develops to be aggressive which is closely related to the chronic inflammatory tumor microenvironment in situ. This study aimed to assess the immunoglobulin G (IgG) subclass of B cells and explore their interactions with T follicular helper (Tfh) subsets in prostate cancer patients. The percentages of peripheral blood naïve B cells, memory B cells and mature B cells, as well as Tfh1, Tfh2 and Tfh17 cells were analyzed or sorted by FACSAria. The ratios of the different IgG subclasses (IgG1, IgG2, IgG3 and IgG4) were detected by ELISA, and the expression levels of CXCR3 and CCR6 were measured using RT-PCR and western blot analysis. Meanwhile a co-culture system of B and Tfh cells was to assess the effect of each Tfh subset on the antibody subclass switching of B cells in vitro. We observed higher percentages of 3 Tfh subsets and IgG4+ B cells in the patients with prostate cancer than that in the health controls and proved a positive correlation between Tfh2 and IgG4+ B cells. Then we verified that IL-4, IL-6, IL-10 and prostaglandin E2 (PGE2) effectively promoted antibody class switching of B cells, which may be mediated by inducing Tfh2 cells, yet the study was not completely dependent on Tfh cells. The results provide evidence of the B cell response to an immune suppressive environment by evaluating IgG4 antibodies, and established a relationship between IgG4+ B cells and Tfh2 cells. Clarification of lymphocyte functions in the inflammatory microenvironment of tumors will be of potential therapeutic value.

Current status of diagnosis and treatment of bladder cancer in China - Analyses of Chinese Bladder Cancer Consortium database.

OBJECTIVE: To investigate current status of diagnosis and treatment of bladder cancer in China. METHODS: A database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected. RESULTS: The average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy. CONCLUSION: Disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China.

Alpha-2-macroglobulin as a radioprotective agent: a review.

Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin (α2M) possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a non-selective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovic et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, anti-fibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of α2M. The lacunae in the existing knowledge and directions for future research are also addressed.

Selective expression of tumor necrosis factor-related apoptosis-inducing ligand mediated by microRNA suppresses renal carcinoma growth.

Renal cell carcinoma (RCC) is the most common types among kidney cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) strongly induces apoptosis in RCC. However, TRAIL therapy also leads to hepatotoxicity. To improve the biosafety, we inserted miRNA response elements (MREs) of miR-138, miR-199, and miR-122 into an adenoviral vector, Ad-TRAIL-3MREs, to restrict TRAIL expression within RCC cells. Luciferase assays showed that MREs can regulate the expression of exogenous gene in RCC cells. Ad-TRAIL-3MREs selectively expressed TRAIL and induce apoptosis in RCC cells, but not in normal cells. MTT assays revealed that Ad-TRAIL-3MREs reduced viability of RCC cells without cytotoxicity to normal cells. Ad-TRAIL-3MREs suppressed the growth of ACHN tumors and exerted no hepatotoxicity in vivo. Collectively, we generated a TRAIL-expressing adenoviral vector under the regulation of MREs. This miRNA-based gene therapy may be a promising strategy for RCC treatment.