Sustained complete response to first-line immunochemotherapy for highly aggressive TP53/MDM2-mutated upper tract urothelial carcinoma with ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state: a case report and literature review.

Background: Upper tract urothelial carcinoma (UTUC) is a rare malignancy. The management of metastatic or unresectable UTUC is mainly based on evidence extrapolated from histologically homologous bladder cancer, including platinum-based chemotherapy and immune checkpoint inhibitor alone, whereas UTUC exhibits more invasiveness, worse prognosis, and comparatively inferior response to treatments. First-line immunochemotherapy regimens have been attempted in clinical trials for unselected naïve-treated cases, but their efficacies relative to standard chemo- or immuno-monotherapy still remain controversial. Here, we present a case of highly aggressive UTUC for whom comprehensive genetic and phenotypic signatures predicted sustained complete response to first-line immunochemotherapy. Case presentation: A 50-year-old man received retroperitoneoscopic nephroureterectomy and regional lymphadenectomy for high-risk locally advanced UTUC. Postoperatively, he developed rapid progression of residual unresectable metastatic lymph nodes. Pathologic analysis and next-generation sequencing classified the tumor as highly aggressive TP53/MDM2-mutated subtype with features more than expression of programmed death ligand-1, including ERBB2 mutations, luminal immune-infiltrated contexture, and non-mesenchymal state. Immunochemotherapy combining gemcitabine, carboplatin, and off-label programmed death-1 inhibitor sintilimab was initiated, and sintilimab monotherapy was maintained up to 1 year. Retroperitoneal lymphatic metastases gradually regressed to complete response. Blood-based analyses were performed longitudinally for serum tumor markers, inflammatory parameters, peripheral immune cells, and circulating tumor DNA (ctDNA) profiling. The ctDNA kinetics of tumor mutation burden and mean variant allele frequency accurately predicted postoperative progression and sustained response to the following immunochemotherapy, which were mirrored by dynamic changes in abundances of ctDNA mutations from UTUC-typical variant genes. The patient remained free of recurrence or metastasis as of this publishing, over 2 years after the initial surgical treatment. Conclusion: Immunochemotherapy may be a promising first-line option for advanced or metastatic UTUC selected with specific genomic or phenotypic signatures, and blood-based analyses incorporating ctDNA profiling provide precise longitudinal monitoring.

piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination.

Accumulating studies have confirmed that PIWI-interacting RNAs (piRNAs) are considered epigenetic effectors in cancer. We performed piRNA microarray expression analysis on renal cell carcinoma (RCC) tumor tissues and paired normal tissues and performed a series of in vivo and in vitro experiments to explore piRNAs associated with RCC progression and investigate their functional mechanisms. We found that piR-1742 was highly expressed in RCC tumors and that patients with high piR-1742 expression had a poor prognosis. Inhibition of piR-1742 significantly reduced tumor growth in RCC xenograft and organoid models. Mechanistically, piRNA-1742 regulates the stability of USP8 mRNA by binding directly to hnRNPU, which acts as a deubiquitinating enzyme that inhibits the ubiquitination of MUC12 and promotes the development of malignant RCC. Subsequently, nanotherapeutic systems loaded with piRNA-1742 inhibitors were found to effectively inhibit the metastasis and growth of RCC in vivo. Therefore, this study highlights the functional importance of piRNA-related ubiquitination in RCC and demonstrates the development of a related nanotherapeutic system, possibly contributing to the development of therapeutic approaches for RCC.

Combination of preoperative plasma fibrinogen and neutrophil-to-lymphocyte ratio to predict the prognosis for patients undergoing laparoscopic nephrectomy for renal cell carcinoma.

This study was conducted to investigate the prognostic significance of a combination of fibrinogen and neutrophil-to-lymphocyte ratio (NLR) named the F-NLR score as a novel indicator and further create nomograms for predicting the prognosis of patients with renal cell carcinoma (RCC) treated with laparoscopic nephrectomy. A total of 425 patients with RCC who underwent laparoscopic nephrectomy were included in this study. Then, we divided the patients based on the cut-off values of their F-NLR score into three categories: F-NLR 2 (both high fibrinogen and NLR), F-NLR 0 (both low fibrinogen and NLR), and F-NLR 1 (remaining patients). Cox regression analysis was performed to investigate the predictive performance of the F-NLR score on overall survival (OS) and cancer-specific survival (CSS). Predictive nomograms of F-NLR were established and internally validated. Time-dependent receiver operating characteristic (ROC) curve analysis was performed to assess the predictive accuracy of the nomogram, NLR, and fibrinogen as prognostic markers. The F-NLR 0, 1, and 2 groups included 226 (53.2%), 147 (34.6%), and 52 (12.2%) patients, respectively. Cox regression analysis showed that a high F-NLR score was significantly associated with poor prognosis and acted as an independent prognostic factor for OS and CSS (all P < 0.05). Predictive nomograms with F-NLR for OS (C-index: 0.773) and CSS (C-index: 0.838) were well developed. Time-dependent ROC results showed that nomograms containing F-NLR had better predictive performance than NLR and fibrinogen. F-NLR score was a novel effective prognostic biomarker for patients with RCC undergoing laparoscopic nephrectomy.

A Cuproptosis-Related Gene Model For Predicting the Prognosis of Clear Cell Renal Cell Carcinoma.

Despite advances in its treatment, patients diagnosed with clear cell renal cell carcinoma (ccRCC) have a poor prognosis. The mechanism of cuproptosis has been found to differ from other mechanisms that regulate cell death, including apoptosis, iron poisoning, pyrophosphate poisoning, and necrosis. Cuproptosis is an essential component in the regulation of a wide variety of biological processes, such as cell wall remodeling and oxidative stress responses. However, cuproptosis-related genes' expression in ccRCC patients and their association with the patient's prognosis remain ambiguous. Evaluation of The Cancer Genome Atlas (TCGA) identified 11 genes associated with cuproptosis that were differently expressed in ccRCC and nearby nontumor tissue. To construct a multigene prognostic model, the prognostic value of 11 genes was assessed and quantified. A signature was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and this signature was used to separate ccRCC patients into different risk clusters, with low-risk patients having a much better prognosis. This five-gene signature, when combined with patients' clinical characteristics, might serve as one independent predictor of overall survival (OS) in ccRCC patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that cuproptosis-related genes were enriched in patients with ccRCC. Then, quantitative real-time PCR (qPCR) was employed to verify these genes' expression. Generally, research has indicated that cuproptosis-related genes are important in tumor immunity and can predict OS of ccRCC patients.

Transfection with Plasmid-Encoding lncRNA-SLERCC nanoparticle-mediated delivery suppressed tumor progression in renal cell carcinoma.

BACKGROUND: The accumulating evidence confirms that long non-coding RNAs (lncRNAs) play a critical regulatory role in the progression of renal cell carcinoma (RCC). But, the application of lncRNAs in gene therapy remains scarce. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA-SLERCC (SLERCC) in RCC cells. METHODS: We performed lncRNAs expression profiling in paired cancer and normal tissues through microarray and validated in our clinical data and TCGA dataset. The Plasmid-SLERCC@PDA@MUC12 nanoparticles (PSPM-NPs) were tested in vivo and in vitro, including cellular uptake, entry, CCK-8 assay, tumor growth inhibition, histological assessment, and safety evaluations. Furthermore, experiments with nude mice xenografts model were performed to evaluate the therapeutic effect of PSPM-NPs nanotherapeutic system specific to the SLERCC. RESULTS: We found that the expression of SLERCC was downregulated in RCC tissues, and exogenous upregulation of SLERCC could suppress metastasis of RCC cells. Furthermore, high expression DNMT3A was recruited at the SLERCC promoter, which induced aberrant hypermethylation, eventually leading to downregulation of SLERCC expression in RCC. Mechanistically, SLERCC could directly bind to UPF1 and exert tumor-suppressive effects through the Wnt/ß-catenin signaling pathway, thereby inhibiting progression and metastasis in RCC. Subsequently, the PSPM-NPs nanotherapeutic system can effectively inhibit the growth of RCC metastases in vivo. CONCLUSIONS: Our findings suggested that SLERCC is a promising therapeutic target and that plasmid-encapsulated nanomaterials targeting transmembrane metastasis markers may open a new avenue for the treatment in RCC.

Novel insights into the roles and therapeutic implications of MUC1 oncoprotein via regulating proteins and non-coding RNAs in cancer.

Mucin 1 (MUC1) is a heterodimeric transmembrane glycoprotein that protects epithelial cells in mammals. The transmembrane C-terminal subunit (MUC1-C) plays a crucial role in oncogenesis. As an oncoprotein, MUC1-C regulates a number of proteins that are associated with tumorigenesis by interacting with oncoproteins, transcription factors, coactivators, etc., inducing proliferation, epithelial-mesenchymal transition (EMT), invasion, stemness, immune evasion, and drug resistance. Moreover, MUC1-C modulates the expression of non-coding RNAs (ncRNAs), which further regulate carcinogenesis by directly binding to specific proteins. ncRNAs can also affect MUC1 protein expression by targeting the MUC1 mRNA 3' untranslated region (UTR). A series of ncRNAs can modulate cancer development by regulating MUC1-C. This review focuses on the interaction of MUC1-C with proteins and ncRNAs in cancer progression. We also summarize the recent advances in immunotherapy with a focus on therapeutic approaches based on MUC1-C and nanocarrier complexes for cancer treatment.

Hypoxia promoted renal cell carcinoma cell migration through regulating lncRNA-ENST00000574654.1.

BACKGROUND: Hypoxia is common in solid tumor masses that has functional consequences for tumor progression. Previous studies demonstrated that nearly 80% renal cell carcinoma (RCC) are under hypoxia. However, effect and its mechanism of hypoxia on RCC cell invasion remains to be defined. METHODS: The shRNA expression vectors, which were constructed to express a short hairpin RNA against lncRNA and overexpression of lncRNA, were transfected into the RCC cell lines (SW839 and OSRC-2). Levels of lncRNA-ENST00000574654.1, VEGF-A and VEGF-C mRNA and protein were examined by real-time quantitative-fluorescent PCR and Western blot analysis, respectively. The effects of lncRNA silencing and overexpression on cell invasion of SW839 and OSRC-2 cells were evaluated with cell migration assay. RESULTS: Hypoxia significantly stimulated cell invasion in both RCC cell lines (SW839: 2.38 ± 0.19 of normoxia vs 7.83 ± 0.38 of hypoxia, P < 0.05; and OSRC-2: 1.00 ± 0.08 of normoxia vs 5.88 ± 0.32 of hypoxia, P < 0.05). LncRNA microarray analysis found that lncRNA-ENST00000574654.1 was down-regulated under hypoxia. Consistently, over-expression of lncRNA-ENST00000574654.1 resulted in significant blockade of hypoxia-induced RCC migration. Furthermore, expression of lncRNA-ENST00000574654.1 was regulated by HIF-1α and VEGA-A through interacting with hnRNP, which in turn regulated the RCC cell invasion. CONCLUSIONS: These findings suggested that hypoxia promoted RCC cell invasion through HIF-1α/lncRNA (ENST00000574654.1)/hnRNP/VEGF-A pathway. Targeting this pathway could potentially improve therapeutic outcomes of renal cell carcinoma.

Expression and clinical value of SALL4 in renal cell carcinomas.

The aim of the present study was to investigate the expression of spalt like transcription factor 4 (SALL4) in the three most common types of renal cell carcinomas (RCC) [clear cell RCC (ccRCC), papillary renal cell carcinoma (pRCC) and chromophobe RCC (chRCC)], and the association with the overall survival (OS) of patients. The Cancer Genome Atlas (TCGA) database and RCC samples were used to investigate the expression levels of the SALL4 gene and its association with the OS in the three types of RCC based on the analysis of the transcriptome, copy number and survival data. It was found that SALL4 was highly expressed in ccRCC and pRCC tumor tissue, and low mRNA expression level of SALL4 indicated a prolonged survival in both ccRCC and pRCC. This mRNA expression level was associated with pathological Tumor­Node­Metastasis stage, M and T stages in both ccRCC and pRCC. The analysis of the enriched pathway results suggested that SALL4 may act via translation initiation, and that the related genes promoted the progression of RCC. Moreover, the high expression level of SALL4 was detected in RCC samples and serum from patients. It was demonstrated that SALL4 promotes increased viability in RCC cells. Therefore, the present results suggest that SALL4 may be a sensitive and specific cancer biomarker in ccRCC and pRCC. Furthermore, targeting of SALL4 may improve RCC therapy and prolong the survival of patients with ccRCC or pRCC.

circPRRC2A promotes angiogenesis and metastasis through epithelial-mesenchymal transition and upregulates TRPM3 in renal cell carcinoma.

Background: Circular RNAs (circRNAs) have been identified as essential regulators in a plethora of cancers. Nonetheless, the mechanistic functions of circRNAs in Renal Cell Carcinoma (RCC) remain largely unknown. Methods: In this study, we aimed to identify novel circRNAs that regulate RCC epithelial-mesenchymal transition (EMT), and to subsequently determine their regulatory mechanisms and clinical significance. Results: circPRRC2A was identified by circRNA microarray and validated by qRT-PCR. The role of circPRRC2A in RCC metastasis was evaluated both in vitro and in vivo. We found that increased expression of circPRRC2A is positively associated with advanced clinical stage and worse survivorship in RCC patients. Mechanistically, our results indicate that circPRRC2A prevents the degradation of TRPM3, a tissue-specific oncogene, mRNA by sponging miR-514a-5p and miR-6776-5p. Moreover, circPRRC2A promotes tumor EMT and aggressiveness in patients with RCC. Conclusions: These findings infer the exciting possibility that circPRRC2A may be exploited as a therapeutic and prognostic target for RCC patients.

Expression and clinical value of CD105 in renal cell carcinoma based on data mining in The Cancer Genome Atlas.

The objective of the present study was to assess the expression of CD105 and its association with overall survival in three subtypes of renal cell carcinoma (RCC), namely clear cell (cc)RCC, papillary (p)RCC and chromophobe (ch)RCC. Data regarding the transcriptome and copy number of genes in RCC tumor samples and survival were obtained from The Cancer Genome Atlas. Bioinformatics analysis revealed that CD105 is overexpressed in ccRCC tumor tissue vs. normal renal tissue, and a higher CD105 copy number in ccRCC tissues was significantly associated with longer patient survival. The effect of the mRNA expression of CD105 in all three types of RCC and the copy number in pRCC and chRCC on patient survival was insignificant, but certain trends were observed. In addition, CD105 mRNA expression was associated with the metastasis and tumor stage, as well as pathological stage in ccRCC and pRCC. Pathway enrichment analysis revealed that CD105 may, through translation initiation of associated genes, promote RCC progression. The results of the present study suggest that in RCC tumors, the association of CD105 with different stages is complex. To evaluate the role of CD105 in RCC, its function should be assessed in addition to its expression. The exact influence of CD105 mRNA expression and copy number in RCC tumors on patient survival and the underlying mechanisms require further elucidation.

The long noncoding RNA HOTAIR activates the Hippo pathway by directly binding to SAV1 in renal cell carcinoma.

The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation. Loss of function of SAV1 activated the Hippo pathway. HOTAIR could be a potential therapeutic target in RCC.

Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae.

The aim of the present study was to compare the efficacy and safety of fosfomycin combinational therapy with other antibiotics for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). This retrospective cohort study examined 104 cases of sepsis caused by CRKP occurring between January 2012 and November 2014 in Shanghai Tenth People's Hospital. Three categories of patient outcome were assessed: Survival/mortality, duration of intensive care unit stays and duration of medical ventilation. Univariate ordinal analyses were adopted to evaluate the correlations between outcome and treatment. A total of 104 patients with physician-diagnosed CRKP were involved in the study. The overall mortality rate was 25.0%. The majority of the infections (84; 80.8%) were hospital acquired. Critical infections received more than one active antibiotic as therapy. Patients treated with fosfomycin combinational therapy were less likely to fail therapy (OR: 4.71, 95% CI: 1.03-21.65, P=0.034) and tended to have a shorter duration of mechanical ventilation. Gender (OR: 4.35, 95% CI: 1.08-3.60, P=0.037), history of chronic obstructive pulmonary disease (OR: 9.35, 95% CI: 0.06-0.19, P=0.007) and peripheral catheter use (OR: 3.00, 95% CI: 0.07-0.19, P=0.002) are risk factors for clinical outcome. Therefore, the use of fosfomycin combinational therapy for treatment of infection due to CRKP appears to be associated with improved survival rate.

Decreased expression of long non-coding RNA NBAT-1 is associated with poor prognosis in patients with clear cell renal cell carcinoma.

OBJECTIVE: accumulating evidence suggest that long non-coding RNAs (lncRNAs) may play important roles in human cancers. LncRNA neuroblastoma associated transcript-1 (NBAT-1) was initially identified to be involved in the progression of neuroblastoma. However, there is no report about the role of NBAT-1 in clear cell renal cell carcinoma (ccRCC). The purpose of this study is to investigate the clinical significant of NBAT-1 in ccRCC. METHODS: the expression pattern of NBAT-1 in ccRCC patients and renal cancer cell lines was detected by using quantitative real-time PCR (qRT-PCR), and its correlation with clinicopathologic features and prognosis of patients with ccRCC was assessed by Kaplan-Meier method and Cox proportional hazards model, respectively. Small interfering RNA (siRNA) was transfected into 786-O and ACHN cells to determine the effect of NBAT-1 knockdown on renal cancer cells. RESULT: NBAT-1 expression is significantly decreased in ccRCC tissues and renal cancer cells compared with adjacent normal tissues and normal human proximal tubule epithelial cell line HK-2, and its low level is associated with advanced features and poor prognosis. Also, multivariate analysis identified NBAT-1 expression as an independent prognostic factor for ccRCC. In vitro assays indicated that knockdown of NBAT-1 expression increased renal cancer cell proliferation, migration and invasion. CONCLUSIONS: NBAT-1 is a novel molecular correlated with ccRCC progression; and it may represent a prognostic biomarker and therapeutic target in renal cancer diagnosis and treatment.

Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels.

Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.

Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma.

Long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, pancreatic cancer, and cervical cancer. However, the role of lncRNA MALAT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. Expression levels of lncRNA MALAT1 in ccRCC tissues and renal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA (siRNA) was used to suppress MALAT1 expression in renal cancer cells. In vitro assays were conducted to further explore its role in tumor progression. The expression level of MALAT1 was higher in ccRCC tissues and renal cancer cells compared to adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. The ccRCC patients with higher MALAT1 expression had an advanced clinical features and a shorter overall survival time than those with lower MALAT1 expression. And multivariate analysis showed that the status of MALAT1 expression was an independent predictor of overall survival in ccRCC. Additionally, our data indicated that knockdown expression of MALAT1 decreased renal cancer cell proliferation, migration, and invasion. Our data suggested that lncRNA MALAT1 was a novel molecule involved in ccRCC progression, which provided a potential prognostic biomarker and therapeutic target.

Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA­21.

Previous studies have reported that hyperoside and quercetin in combination (QH; 1:1) inhibited the growth of human leukemia cells. The aim of the present study was to investigate the anti­cancer effect of QH on prostate cancer cells. The results demonstrated that QH decreased the production of reactive oxygen species (ROS) and increased antioxidant capacity in PC3 cells at various concentrations (2.5­60 µg/ml) with peak inhibition and augmentation changes of 3.22­ and 3.00­fold, respectively. Following treatment with QH for 48 and 72 h, the IC50-values on PC3 cells were 19.7 and 12.4 µg/ml, respectively. Western blot analysis revealed that QH induced apoptosis in human prostate cancer cells via activation of caspase­3 and cleavage of poly(adenosine diphosphate ribose) polymerase. In addition, QH significantly inhibited the invasion and migration of PC3 cells as well as reduced the expression of numerous prostate tumor­associated microRNAs (miRs), including miR­21, compared to that of untreated human prostate cancer cells. QH was also found to enhance the expression of tumor suppressor programmed cell death protein 4, which was negatively regulated by miR­21. Furthermore, induced overexpression of miR­21 using pre­miR­21 oligonucleotides attenuated the beneficial effect of QH on prostate cancer cells. In conclusion, the results of the present study indicated that QH exerted an anti­cancer effect on human prostate cancer cells, the mechanism of which proceeded, at least in part, via the inhibition of the miR­21 signaling pathway.

Metformin inhibits cell growth by upregulating microRNA-26a in renal cancer cells.

Accumulating evidence suggests that metformin, a biguanide class of anti-diabetic drugs, possesses anti-cancer properties and may reduce cancer risk and improve prognosis. However, the mechanism by which metformin affects various cancers, including renal cancer still unknown. MiR-26a induces cell growth, cell cycle and cell apoptosis progression via direct targeting of Bcl-2, clyclin D1 and PTEN in cancer cells. In the present study, we used 786-O human renal cancer cell lines to study the effects and mechanisms of metformin. Metformin treatment inhibited RCC cells proliferation by increasing expression of miR-26a in 786-O cells (P < 0.05). As a result, protein abundance of Bcl-2 and cyclin D1 was decreased and PTEN was increased in cells exposed to metformin. Also over-expression of miR-26a can inhibited cell proliferation by down-regulating Bcl-2, cyclin D1 and up-regulating PTEN expression. Therefore, these data for the first time provide novel evidence for a mechanism that the anticancer activities of metformin are due to upregulation of miR-26a and affect its downstream target gene.

High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma.

INTRODUCTION: Long non-coding RNAs (lncRNAs) play a key role in cellular processes, such as cell growth, apoptosis, and carcinogenesis. lncRNAs SPRY4-IT1 has recently been identified to be involved in tumorigenesis of several cancers such as non-small cell lung cancer and esophageal squamous cell carcinoma. However, the role of SPRY4-IT1 in clear cell renal cell carcinoma (ccRCC) remains unclear. METHODS: The expression of SPRY4-IT1 was examined in ccRCC patients and renal cancer cell lines by using quantitative real-time PCR (qRT-PCR). The relationship between SPRY4-IT1 level and clinicopathological parameters of ccRCC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in renal cancer cell line 786-O. In vitro assays were performed to further explore its role in renal cancer progressio. RESULTS: The relative level of SPRY4-IT1 was significantly higher in ccRCC tissues compared to the adjacent normal renal tissues. And higher expression of SPRY4-IT1 was found in renal cancer cell lines compared with the normal human proximal tubule epithelial cell line HK-2. The ccRCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. Multivariate analyses by Cox's proportional hazard model revealed that expression of SPRY4-IT1 was an independent prognostic factor in ccRCC. In vitro assays, our results indicated that knockdown of SPRY4-IT1 reduced renal cancer cell proliferation, migration, and invasion. CONCLUSIONS: Our data suggested that lncRNA SPRY4-IT1 might be considered as a potential prognostic indicator and a potential target for therapeutic intervention in RC.

Metastatic prostate adenocarcinoma posing as urothelial carcinoma of the right ureter: a case report and literature review.

This is a case report of a 67-year-old patient with distant metastasis of prostate cancer to the right ureter which caused hydronephrosis. At the beginning, both of the cytology of the morning urine and imaging findings were consistent with urothelial carcinoma. Nephroureterectomy was subsequently performed. Interestingly, the pathological examination of the excised ureter revealed that the malignancy was derived from the prostate. No skeletal metastasis was detected. However, after four months of follow-up, several abnormal signal shadows were reported in skeletal scintigraphy and the prostate specific antigen (PSA) was gradually increasing. We present such a case for its unique presentation. A review of the literature is also provided.

Prophylactic effects of quercetin and hyperoside in a calcium oxalate stone forming rat model.

Quercetin and hyperoside (QH) are the two main constituents of the total flavone glycosides of Flos Abelmoschus manihot, which has been prescribed for treating chronic kidney disease for decades. This study aimed to investigate the effect of QH on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. Rats were divided into three groups: an untreated stone-forming group, a QH-treated stone-forming group (20 mg/kg/day) and a potassium citrate-treated stone-forming group (potassium citrate was a worldwide-recognized calculi-prophylactic medicine). Ethylene glycol (0.5 %) was administered to the rats during the last week, and vitamin D3 was force-fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. 24 h urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope for semi-quantification of the crystal-formation. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. QH and potassium citrate have the ability to alkalinize urine. The number of crystal deposits decreased significantly in the QH-treated stone-forming group as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the QH-treated stone-forming group, as compared with the untreated stone-forming group. QH administration has an inhibitory effect on the deposition of CaOx crystal in EG-fed rats and may be effective for preventing stone-forming disease.