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Background In the era of individualized therapy,there is a great need to incorporate lncRNAs into preclinical models to develop prognostic or therapeutic biomarkers.We sought to apply the tumor immune-associated lncRNA – SNHG16 to develop and validate a predictive model constructed from SNHG16 and associated immune gene signatures in BC patients obtained from independent public datasets and clinical internal cohorts, to assess the benefit of immune checkpoint inhibitors treatment and the prognosis in BC patients. Materials and methods A novel immune-related and independent predictive model was developed for prognosis and immunotherapeutic evaluation of bladder cancer, based on the identification and analysis of the immune-related SNHG16. Based on the training (TCGA-BLCA) and external validation datasets, the SNHG16-associated immune gene signature was applied to classify BC patients into low- and high-risk groups. Cell proliferation assay and Transwell assay were used to detect the function of related genes. Results There were significant differences in prognosis and response to immunotherapy among patients in the different risk groups. Univariate and multivariate analyses confirmed the SNHG16-associated immune gene signature to be an independent predictor of BC prognosis. In addition,in vitro functional assay data confirmed the cancer biological function of SNHG16 and its associated immune signature genes. Conclusions Immune-associated lncRNA-SNHG16 and its associated immune gene signatures are reliable tools for predicting BC prognosis and response to immunotherapy and may provide valuable insights for deciding the treatment for BC. Further, the model will provide useful guidance for clinical judgment and personalized regimen-selection for immunotherapy of bladder tumors.

Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an angiotensin II receptor blocker (ARB) and has been shown to exhibit renoprotective effects on a streptozotocin (STZ)-induced diabetic rat model. Yet, whether OM affects DN progression and renal injury in db/db mice, a type 2 diabetic murine model, has not been established. Methods Wild-type (n = 15) and db/db mice (n = 15) were treated with control saline or OM via oral gavage. The physiological and biochemical parameters were evaluated and histological examinations of kidney specimens were performed. Results Compared with saline-treated db/db mice, db/db mice administered with OM showed ameliorated diabetic physiological and biochemical parameters. In addition, OM decreased urinary albumin excretion and plasma creatinine level in db/db mice. Moreover, histologically, OM reduced glomerular hypertrophy and injury, and also ameliorated tubular injury, thus suggesting that OM improves renal function and minimizes renal pathological deterioration in db/db mice. Conclusion Our study reveals a beneficial role of OM in ameliorating DN in db/db mice, which is associated with its renoprotective function.

Background The non-receptor tyrosine kinase Fyn-related kinase (FRK) has been reported to affect cell proliferation in several cancer types. However, its effect on the proliferation of clear cell renal cell carcinoma (ccRCC) remains largely unknown. Purpose The objective of this study was to investigate the expression pattern and function of FRK in ccRCC. We further determined how FRK interacted with other molecules to regulate ccRCC proliferation. Patients and methods The expression of FRK in ccRCC samples and paired normal renal tissues from 30 patients were analyzed by immunoblotting, immunohistochemistry and quantitative PCR. Then the role of FRK in ccRCC proliferation was analyzed by Cell Counting Kit-8, colony formation assay and EdU incorporation assay. In addition, the miRNA targeting FRK was predicted through a bioinformatic approach and validated by quantitative PCR, immunoblotting and luciferase reporter assay. Finally, the underlying mechanism of FRK regulation of ccRCC proliferation was also determined. Results Low expression of FRK was detected in ccRCC samples and predicted poor survival for ccRCC patients. FRK inhibited the proliferation of ccRCC cells via phosphorylating downstream PTEN. miR-19 was identified as a novel suppressor of FRK in renal cancer cells and it promoted the proliferation of ccRCC by inhibiting the FRK–PTEN axis. Conclusion Our results unravel a new regulatory mechanism involved in ccRCC proliferation and may be useful in the identification of therapeutic targets for ccRCC.

Cost-effective nitrogen-doped monolithic hierarchical carbon cryogels with excellent mechanical properties and carbon dioxide (CO

MicroRNAs (miRNAs) are small, noncoding ribonucleic acids (ncRNAs), which regulate gene expression by targeting mRNAs for translational repression and degradation. Several lines of evidences have indicated that miRNAs act as tumor suppressors and oncogenes. However, the role of miRNAs in pathogenesis of multiple myeloma (MM) remains unclear. In this study, we examined the profile of miRNA expression of primary MM cells, using miRNA microarray and quantitative real-time polymerase chain reaction (qPCR) techniques. These results showed that in the bone marrow specimens analyzed, miRNA-29b was significantly downregulated. Similar results were also observed in human myeloma cell lines (HMCLs). Adenovirus-mediated overexpression of miR-29b induced apoptosis and elevated caspase-3 activation in HMCLs. Using a bioinformatics approach, we found a perfect complementarity between miRNA-29b and the 3'UTR of myeloid-cell-leukemia 1(Mcl-1). It is further confirmed that miRNA-29b downregulated the level of Mcl-1 without effect on the mRNA level using both qRT-PCR assays and Western blot analyses. Moreover, we observed that enforced miR-29b expression by using a retarget miRNA-29b expression vector (Ad5F11p-miR-29b) could induce apoptosis and elevate caspase-3 activation in HMCLs. Our results also indicated that miRNA-29b-induced apoptosis acted antagonistically with IL-6 in HMCLs. These findings suggest that miRNA-29b may play an important role in MM as a tumor suppressor.

Human adenovirus type 41 (HAdV-41) is difficult to cultivate under laboratory conditions. Tripartite leader sequence (TPL) of HAdV-41 was cloned, inserted into eukaryotic expression plasmid, and used to establish a HAdV-41 E1B55K-transduced cell line (293TE7). HAdV-41 E1B55K was expressed more abundantly in 293TE7 than in 293E12, an HAdV-41 E1B55K-expressing cell line developed previously. After being infected with E1-deleted HAdV-41 vector (HAdV-41-GFP), 293TE7 synthesized more viral genomic DNA and structural proteins, which led ultimately to a significant increase of the yield of progeny viruses. Typically, 293TE7 produced progeny viruses 3-15 times more than 293E12 did, depending on the amount of seed viruses and culture time. These data demonstrated that 293TE7 was an effective packaging cell line, and implied its application for wild-type HAdV-41 isolation, HAdV-41 virological study and recombinant HAdV-41 construction.

Genital rhabdomyoma is very rare tumor that usually occurs in the vulvar of young women. Epididymis rhabdomyoma in a young man is extremely uncommon and has rarely been reported. Here, we report a case of epididymis rhabdomyoma of a 17-year-old man and review the literatures. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1177628224692794

To investigate the experience on diagnosis and treatment of multiple adrenal aldosterone-producing adenomas (APA).Eighteen cases of multiple adrenal APA were analyzed retrospectively, which were admitted from October 1992 to April 2006.Adrenalectomy was performed for 4 cases of unilateral synchronous multiple APA, which were discovered with three adenomas by 3D-CT; bilateral tumor resection was performed for 6 cases of bilateral synchronous multiple APA. There were 8 cases of bilateral metachronous multiple APA, including 2 cases of ipsilateral recurrent adrenal APA after adrenal tumor removal, which underwent tumor resection. Another 6 cases were contralateral APA following adrenalectomy due to adrenal APA, and underwent tumor resection. After operation, the adrenal function seemed to be normal, and no recurrence had been found on follow-up.Unilateral multiple synchronous APA require adrenalectomy. Tumor resection should be performed for bilateral or asynchronous APA, and it is very important to preserve healthy adrenal tissue as much as possible. 3D-CT has much value on diagnosis of small APA, unilateral multiple synchronous APA and ipsilateral recurrent adrenal APA.

The purpose of this study is to investigate if the aqueous extract of the Chinese medicine Danggui-Shaoyao-San (DSS) can increase the plasma level of melatonin and enhance the function of the pineal gland of naturally aged rats.The rats were treated with DSS at doses of 3ml or same volume of distilled water by oral administration at 11 p.m. for three weeks. The plasma level of melatonin were measured by radioimmunoassay. The function of pineal gland were measured through three parameters: pineal beta adrenergic receptor binding investigated by [3H]DHA binding; pineal expression of NAT mRNA detected by real-time RT-PCR; phosphorylation of CREB (P-CREB) and total level of CREB (T-CREB) measured by western blot analysis.DSS significantly increased melatonin level at night after oral administration for 3 weeks. By measurement of pineal [3H]DHA binding, it was found DSS improved the beta-adrenergic receptors binding in pineals. The stimulatory effect of DSS on the expression of NAT mRNA in the old rat pineal gland has been demonstrated in this study. Western blot analysis showed that DSS significantly increased phosphorylation of CREB.Our results indicate that a downstream pathway for DSS induction of melatonin synthesis in the rat pineal gland acts via cyclic AMP-dependent cascade and transcription mechanism.

To evaluate the diagnosis and treatment of hereditary renal cell carcinoma.Clinical data of 11 patients with hereditary renal cell carcinoma were analyzed retrospectively. Eight patients were male and 3 were female, age ranged from 32 to 67 (mean: age 48 years). Four cases were bilateral renal cell carcinoma, and 4 were multiple renal cell carcinoma. Two cases were diagnosed as Von Hippel-Lindau syndrome, 6 as familial clear cell renal cell cancer, and 3 as hereditary papillary renal carcinoma.Ten patients performed nephron-sparing surgery and/or radical nephrectomy and 1 had no operation. The patients were followed up from 12 to 114 months. Tumor recurrence was observed in 4 patients, 1 patient died of tumor metastasis, and 2 died of other causes. Four patients survived free of tumor.Hereditary renal carcinoma appears in the youth, and it is predominantly multiple and bilateral. Nephron-sparing surgery is the standard method of treatment for the patients.

To determine the expression of bone morphogenetic protein 2 and 4 (BMP-2 and BMP-4) in prostatic carcinoma (PCa) and investigate their relationship with clinical stage and Gleason score of tumor.Forty-eight PCa cases and 5 normal prostatic tissue were analysed for the expressions of BMP-2 and BMP-4 by Western bolt assay.The optical densities of BMP-2 expressions in the tumor with Gleason scoreor =5, 6-8, andor = 9 were 7547.1 +/- 1964.12, 9657.4 +/- 2010.54, 12467.7 +/- 2496.75 and of BMP-4 expressions were 5174.4 +/- 1400.54, 5940.3 +/- 1587.42, 6332.1 +/- 1647.83, respectively. The optical densities of BMP-2 expressions in the tumor in T1 - T2 and T3 - T4 stages were 8003.37 +/- 1889.23, 12385.55 +/- 2506.72 and of BMP4 expressions were 5267.41 +/- 1 464.19, 6543.75 +/- 1668.46, respectively. There were significant differences between tissues with Gleason scoreor =5 andor =9 (P0.01), and tissues in T1 - T2 and T3 - T4 stages, in expressions of BMP-2 protein. The expression of BMP-2 protein was significantly high in the PCa with bone metastasis compared with that without bone metastasis.The expressions of BMP-2 and BMP-4 increase with the progression of clinical stage and Gleason score compared with normal prostatic tissue. The expression of BMP-2 protein is significantly upregulated in bone metastasis of PCa, which indicates a poor prognosis.

To investigate the expression of TGF-beta1 mRNA in prostate carcinoma tissues and its significance.RT-PCR method was used to examine the expression of TGF-beta1 mRNA in normal and carcinomatous prostate tissues.The relative content of TGF-beta1 mRNA of normal prostate tissues was (0.74 +/- 0.11), while those of carcinomatous prostate tissues at T1-T2 and T3-T4 stages were (0.69 +/- 0.10) and (0.44 +/- 0.08) respectively, with significant difference between T1-T2 and T3-T4 (P0.05). And the relative contents of TGF-beta1 mRNA of carcinomatous prostate tissues with Gleason scoreor = 5, 6-8 andor = 9 were (0.70 +/- 0.12), (0.54 +/- 0.11) and (0.42 +/- 0.09) respectively.The expression of TGF-beta1 mRNA was negatively correlated with the clinical stage and Gleason score of prostate carcinoma.

To investigate the relationship of protein kinase C-alpha (PKCalpha) expression/activation with tumor differentiation and resistance to chemotherapy drugs in superficial bladder carcinoma.Expression of PKCalpha was measured by Western-blot analysis in 76 samples including tumor and normal tissues, respectively. A human RT4 bladder cancer cell line stably expressing green fluorescent protein (GFP)-PKCalpha (RT4/PKCalpha) was established. The sensitivity of the RT4/PKCalpha and parental cells to adriamycin (ADM) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The change of sensitivity of the RT4/PKCalpha to ADM were observed under the conditions of PKC activation and inhibition, respectively.Total level of PKCalpha expression and the ratio of the amount of PKCalpha expression or PKC activity in membrane to that in cytosol (M/C) were all more higher in cancerous tissues than in normal tissues (P0.01); With the increase of tumor grade, the relative level of PKCalpha expression significantly increased in membrane (P0.01) and decreased in cytosol (P0.01), M/C of PKCalpha was significantly elevated (P0.01), and total relative level of PKCalpha expression significantly increased (P0.01). Thirty-eight cases recurred during the follow-up period in total seventy cases. Multivariate analysis showed that high M/C of PKCalpha was independent prognostic factor for tumor recurrence after standard ADM treatment in the 2-year follow-up (RR = 3.98, 95% CI 1.22-5.68, P = 0.03). Transfection of PKCalpha increased resistance of RT4 cells to ADM [resistance index (RI): 6.97, t = 3.24, P0.01]. PKCalpha activation further greatly promoted the resistance (RI: 148.11, t = 5.18, P0.001) while inhibition of PKCalpha did conversely (RI: 1.6, t = 1.29, P0.05).The abnormal activation and expression level of PKCalpha closely correlate with both tumor grade and intrinsic resistance to ADM in patients with superficial bladder carcinoma.

To investigate the role of lung resistance-related protein (LRP) in intrinsic multidrug resistance (MDR) of bladder cancer and detect the relationship of LRP expression with the clinical pathologic parameters.66 patients were studied with newly diagnosed primary bladder cancer (T(a) = 12, T(1) = 26, T(2) = 11, T(3) = 10, T(4) = 7; G(1) = 35, G(2) = 19, G(3) = 12). No patient was treated preoperatively with either radiation or chemotherapy. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for measure of mRNA expression for LRP, multidrug-resistance gene 1 (MDR1), and multidrug resist nce-associated protein 1 (MRP1). Expressions of LRP, P53 and P63 proteins were examined by immunohistochemistry staining.LRP mRNA had the highest expression rate (64%, 42/66) among three MDR markers in primary bladder cancers without chemotherapy and its level was significantly higher in normal bladder tissue than in TCC of bladder (t = 2.82, P0.01), in low grade than in high grade cancers (t = 4.14, P0.01), and in superficial than in invasive cancers (t = 3.58, P0.05). LRP mRNA expression showed no correlation with either MDR1 or MRP1, but close correlation with LRP protein level (r = 0.89, P0.01). LRP was associated with low-grade (r = 0.81, P0.01) and low-stage (r = 0.78, P0.05) cancers, but not with tumor suppressor P53 or P63 (P0.05).The grade and stage-related expression pattern of LRP indicates that it may be a predictive index for intrinsic MDR in bladder cancer. Anti-cancer drugs out of the MDR spectrum of LRP may be more effective for patients with early bladder cancer.

To study the clinical features, treatment and diagnosis of parapelvic cyst.Twenty-three patients of parapelvic cyst of the kidney were reviewed retrospectively. Fourteen cases (61%) complained of lumbar pain or discomfort, and 4 patients (17%) accompany hematuria and hypertension.In 15 patients receiving surgery, 2 were treated by nephrectomy, one by radical nephrectomy for misdiagnosis. Postoperative diagnosis confirmed a cyst. Eight patients were treated conservatively for cyst being small and without clinical symptoms. Nineteen cases were followed up for 0.5 - 12.0 years.Ultrasonography and CT scan are the main diagnostic methods. Enhanced CT is extremely helpful in differential diagnosis of hydronephrosis. Surgical management is suitable for big cysts, lumbar pain, hematuria, hypertension and other complications.