Shangqi Yang

Ketamine-Associated Urinary Tract Dysfunction: An Underrecognized Clinical Entity

Introduction: The use of ketamine as a recreational drug is on the increase among young adults attending clubs and parties. Recreational ketamine users have anecdotally reported increased lower urinary tract symptoms while using the substance. Methods: We describe the severe lower urinary tract symptoms experienced in 6 patients with chronic recreational ketamine use. We obtained a detailed history and physical examination along with further investigation to identify a relationship between recreational ketamine use and these symptoms. Results: The urine cultures were sterile in all cases. Intravenous urography was performed in 3 patients and demonstrated bilateral upper ureteric narrow, mild bilateral hydronephrosis and contracted bladder urodynamic studies showed detrusor instability with urinary leakage when the bladder was filled to a capacity of 30– 50 ml. Cystoscopy revealed a small capacity bladder with erythematous lesions throughout the bladder. Bladder biopsies were performed in 3 patients and showed up as chronic cystitis. Ketamine cessation along with intravesical sodium hyaluronate solution appeared to provide some symptomatic relief. Conclusion: Ketamine-associated urinary tract dysfunction appears to be a relatively new clinical phenomenon. The pathological mechanism of ketamine-associated urinary tract dysfunction is unknown and current management strategies are ketamine cessation along with intravesical sodium hyaluronate solution.

microRNA-184 functions as tumor suppressor in renal cell carcinoma

microRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding RNA molecules of approximately 22 nucleotides in length that function as post-transcriptional gene regulators. Their aberrant expression may be involved in human diseases, including cancer. Although miRNA-184 (miR-184) has been reported in other tumors, its function in renal cell carcinoma (RCC) is still unknown. The aim of the present study was to investigate the role of miR-184 in RCC. The impacts of miR-184 on cell migration, proliferation and apoptosis were evaluated using migration scratch, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assay. Our studies revealed that miR-184 mimic significantly inhibits cell migration, suppresses cell proliferation and induces renal cancer cell apoptosis in vitro when compared with the negative control (P<0.05). In this study, it was observed that miR-184 played a significant role as a tumor suppressor in RCC. Therefore, miR-184 may be a promising therapeutic target for renal cancer treatment in the future.

Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, which is associated with poor prognosis and high recurrence. Long non‑coding RNAs (lncRNAs) have been reported to be dysregulated in cancer and to be important in the regulation of carcinogenesis, thus suggesting that this class of molecules may be used as biomarkers in cancer. The lncRNA urothelial carcinoma associated 1 (UCA1) has been observed to be upregulated and to function as an oncogene in certain types of cancer; however, the role of UCA1 in RCC remains to be elucidated. The present study aimed to determine the expression and function of UCA1 in RCC. Quantitative polymerase chain reaction (qPCR) was used to determine the expression levels of UCA1 in 46 paired RCC and adjacent normal tissue samples. Furthermore, qPCR was used to determine the expression levels of UCA1 in four RCC cell lines compared with the human embryonic kidney 293T cell line. The impact of UCA1 on cell migration, proliferation and apoptosis was investigated by wound scratch assay, MTT and flow cytometry, respectively. The results of the present study demonstrated that UCA1 expression levels were significantly increased in RCC tissues and cells, as compared with the controls. Ectopic expression and gene silencing of UCA1 in RCC cell lines exerted opposite effects on cellular proliferation, migration and apoptosis, and the results suggested that UCA1 may function as an oncogene in RCC. These results indicated that UCA1 may be considered as a promising biomarker for diagnosis, and a therapeutic target in RCC. Further research is required to elucidate the role and target genes of UCA1 in RCC.

Tumor suppressive miR-196a is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma.

Certain microRNAs (miRs) are implicated in the genesis and progression of various cancers by regulating multiple cellular processes, including apoptosis, proliferation and migration. The aim of the present study was to explore the functions of miR‑196a in renal cell carcinoma (RCC). RCC and paired normal tissues we assessed for miR‑196a expression by reverse-transcription quantitative PCR. Furthermore, the effects of miR‑196a on renal cell proliferation, apoptosis and migration were determined using an MTT assay, flow cytometry and a scratch wound assay following restoration of miR-196a with synthetic mimics. miR‑196a was found to be significantly downregulated in RCC tissues compared with that in normal tissues (P<0.05). In addition, miR‑196a suppressed cell proliferation, apoptosis and migration of the 786‑O and ACHN RCC cell lines. To the best of our knowledge, the present study was the first to report this tumor suppressor role of miR‑196a in RCC. The results indicated that miR‑196a may be a potential diagnostic biomarker for RCC and that transfection of miR-196a mimics may represent a novel treatment strategy for RCC.

Upregulated microRNA-16 as an oncogene in renal cell carcinoma

MicroRNAs (miRs) are small, endogenous noncoding RNAs that serve a significant function in various biologic processes, including those involved in cancer. The present study aimed to determine the expression and function of miR-16 in renal cell carcinoma (RCC). Quantitative polymerase chain reaction was used to quantify the expression of miR-16 in 48 paired RCC tissues and adjacent normal tissues. The impact of miR-16 on cell proliferation, migration and apoptosis was analyzed by transfecting miR-16 mature molecules into the renal cancer cell lines 786-O and ACHN. The results indicated that miR-16 was significantly upregulated in RCC tissues (P<0.05). Downregulation of miR-16 resulted in reduced cell proliferation and migration and increased levels of apoptosis, while overexpression of miR-16 resulted in accelerated cellular proliferation and migration, suggesting that miR-16 may function as an oncogene in RCC. The present study demonstrated for the first time, to the best of our knowledge, that miR-16 is upregulated in RCC and acts as an oncogene by inducing cellular proliferation, migration and reducing apoptosis. Further study of miR-16 in RCC may clarify the molecular mechanisms of RCC carcinogenesis and aid in the development of novel biomarkers and therapeutic options.

MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma

microRNAs (miRNAs; miR) are a class of small non-coding RNA molecules, which are involved in the pathogenesis of human diseases through the negative regulation of gene expression. Previous studies have demonstrated that miR-509-3p is a novel miRNA associated with cell proliferation and migration in 786-O renal cell carcinoma (RCC) cells. However, the mechanism of action of miR-509-3p in RCC remains to be elucidated. The present study aimed to examine the functional role and mechanism of miR-509-3p in the development of RCC. The results demonstrated that the expression levels of miR-509-3p were downregulated in the 786-O and ACHN RCC cell lines compared with the normal tissues of 10 patients with RCC, as determined by reverse transcription-quantitative polymerase chain reaction. The mRNA expression levels of mitogen-activated protein kinase kinase kinase 8 (MAP3K8) were upregulated in the RCC cell lines. Functional investigations demonstrated that the overexpression of miR-509-3p inhibited the migration and proliferation of the RCC cells, as determined by wound scratch and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Luciferase reporter assays revealed that the overexpression of miR-509-3p reduced the transcriptional activity of MAP3K8. Furthermore, the present study demonstrated that the ectopic transfection of miR-509-3p led to a significant reduction in the mRNA and protein expression levels of MAP3K8 in the RCC cells. Finally, knockdown of MAP3K8 inhibited the migration and proliferation of the RCC cells. Therefore, the results of the present study demonstrated that the miR-509-3p RCC suppressor was a significant regulator of the MAP3K8 oncogene, suggesting that it may have a potential therapeutic role in the treatment of RCC.

Identification of miR‑125a‑5p as a tumor suppressor of renal cell carcinoma, regulating cellular proliferation, migration and apoptosis

miR‑125a‑5p has been previously described as a tumor suppressor in numerous malignancies, however the expression and function of miR‑125a‑5p in renal cell carcinoma (RCC) remains to be elucidated. In the present study, to explore the potential role of miR‑125a‑5p in RCC, quantitative polymerase chain reaction was used to determine the expression levels of miR‑125a‑5p in renal cancer tissues. The influence of miR‑125a‑5p on cell proliferation, migration and apoptosis was also determined, using an MTT assay, a wound scratch assay and flow cytometry, respectively. The expression of miR‑125a‑5p was shown to be decreased in RCC and the restoration of miR‑125a‑5p by synthetic mimics was shown to suppress cell proliferation and migration, and induce apoptosis. The present results indicate that miR‑125a‑5p may function as a tumor suppressor in RCC. The present study is, to the best of our knowledge, the first to demonstrate the downregulation of miR‑125a‑5p in RCC, and to show the role it has in affecting cellular proliferation, migration and apoptosis. Further research is needed to define the target genes of miR‑125a‑5p and explore the potential of miR‑125a‑5p as a diagnostic or a prognostic biomarker for RCC.

MicroRNA-451a is associated with cell proliferation, migration and apoptosis in renal cell carcinoma

MicroRNAs (miRNAs) are an important class of small, non‑coding RNA molecules that regulate gene expression at the transcriptional or post‑transcriptional level. They are involved in apoptosis, proliferation and migration and are known to have an important role in many types of cancer. Aberrant expression of miRNA‑451a (miR‑451a) has previously been reported in tumors, however its role in renal cell carcinoma (RCC) is currently unknown. The aim of the present study was to investigate the role of miR‑451a in RCC. The expression of miR‑451a was analyzed in 50 paired RCC and normal tissues by quantitative polymerase chain reaction. Furthermore, the effects of miR‑451a on cell migration, proliferation and apoptosis were evaluated, using migration scratch, MTT and flow cytometric assays. The present study demonstrated that miR‑451a was upregulated in RCC, as compared with paired normal tissues (P<0.05). Downregulation of miR‑451a using a synthesized inhibitor, significantly suppressed cell migration and proliferation, and induced apoptosis of renal cancer cells in vitro, as compared with a negative control (P<0.05). In the present study, it was determined that miR‑451a may have an important role as a tumor enhancer in RCC. These results imply that miR‑451a may be a promising therapeutic target for the treatment of RCC.

Investigating urachal carcinoma for more than 15 years

Urachal carcinomas are rare bladder malignances, which usually present at an advanced stage with a high risk of distant metastases and a poor prognosis. To improve understanding of this uncommon carcinoma, a retrospective review was conducted for the cases observed at Peking University Shenzhen Hospital and Peking University First Hospital. The clinical outcomes were analyzed for 17 patients with a diagnosis of urachal cancer, who were admitted to Peking University Shenzhen Hospital (Shenzhen, China) and Peking University First Hospital (Beijing, China) between 1998 and 2013. The TNM staging system was used to predict outcomes. Among the 17 study patients, there were 10 males and seven females, with a median age at diagnosis of 50 years. A total of four (23%) patients presented with lymph node or distant metastasis. The median overall survival time for all stages was 57.6 months, with five patients (38.4%) alive for more than five years following treatment. The application of the TNM staging system demonstrated a median survival time of 6.2 years for stage I/II patients, compared with a median survival of 1.8 years (log-rank, P<0.001) for patients with advanced disease (stages III and IV). In addition, no significant correlation was observed between tumor size and age, and survival. In conclusion, urachal carcinomas are usually locally advanced at presentation. Surgical excision remains the predominant choice of treatment and lymph node dissection is not required unless lymph node involvement is confirmed by preoperative examination. The current results indicated that the most significant predictor of prognosis was the tumor grade.

Resiniferatoxin for treatment of lifelong premature ejaculation: A preliminary study

To evaluate the efficacy of resiniferatoxin in the treatment of patients with lifelong premature ejaculation.