Impact of perioperative blood transfusion on prognosis after nephrectomy in patients with renal cell carcinoma: A meta-analysis and systematic review.

BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse prognosis in several malignancies. For renal cell carcinoma (RCC), the effect of PBT is still debated. OBJECTIVE: To evaluate the impact of PBT on prognosis after nephrectomy in patients with RCC. METHODS: This study is A systematic review and meta-analysis of published article data (PRISMA protocol) for literature related to PBT and RCC through extensive search of EMBASE, Medline via PubMed, Web of Science and Cochrane Library, language limited to English, with no time constraint until May 20, 2022. We pooled the results of multivariable cox regression analyses from each study, with subgroup analyses by dose and timing of transfusion. All analyses were done using Stata14. RESULTS: A total of 12 studies involving 27,683 participants were included. Our meta-analysis pooled the results of multivariable cox regression analysis in each study, showing that PBT is associated with higher overall Mortality (OM; hazard ratio [HR] = 1.34, 1.23-1.44), cancer-specific mortality (CSM; HR = 1.35, 1.20-1.51), and disease recurrence (HR = 1.54, 1.18-1.89). when only patients with nonmetastatic RCC were included, PBT was still associated with higher OM (HR = 1.29, 1.11-1.47) and disease recurrence (HR = 1.58, 1.18-1.98), but the association with CSM (HR = 1.26, 0.99-1.52) was not statistically significant. In subgroup analysis by transfusion dose, small (1-2) units of PBT were not associated with CSM (HR = 1.84, 0.95-2.73), but large (≥3) units were associated with higher CSM (HR = 2.98, 1.74-4.22) and disease recurrence (HR = 1.99, 1.31-2.67). Each additional unit of PBT resulted in a higher CSM (HR = 1.07, 1.04-1.10). In subgroup analysis by transfusion timing, intraoperative transfusion was associated with higher CSM and disease recurrence, but postoperative transfusion was not. CONCLUSIONS: PBT is associated with higher OM, CSM and disease recurrence. This adverse effect seems to be particularly significant in high-dose intraoperative transfusion. It is necessary to limit the overuse of PBT, especially high-dose intraoperative transfusion, in order to improve the prognosis of patients undergoing nephrectomy for RCC.

Association between erectile dysfunction and Helicobacter pylori, folic acid, vitamin B12, and homocysteine: a cross-sectional study.

Background: Previous studies have shown that Helicobacter pylori (Hp) infection is associated with erectile dysfunction (ED), but the mechanism is unclear. Aim: To assess the relationship between ED and Hp, folic acid (FA), vitamin B12 (B12), and homocysteine (HCY). Methods: This study included 84 patients with ED and 42 healthy men. We adopted an IIEF-5 score <21 (5-item International Index of Erectile Function) as the diagnostic criterion for ED, and the RigiScan monitoring device was used to preliminarily screen for and rule out psychogenic ED. Outcomes: Levels of Hp immunoglobulin G (Hp-IgG) titer, FA, B12, and HCY were compared between the ED group and the non-ED group, and the correlation between the indicators was evaluated. Results: The median Hp-IgG titer was higher in the ED group than the control group (32.34 vs 20.88, P < .001). The ED group had lower median levels of B12 (195 vs 338, P < .001) and FA (4.66 vs 10.31, P < .001) and a higher median level of HCY (12.7 vs 8.1, P < .001). Multivariate logistic regression analysis showed that the level of FA (odds ratio, 0.111; 95% CI, 0.031-0.399; P < .001) was an independent risk factor for ED. Specifically, FA level was significantly higher in the moderate ED group than the severe ED group, which had a higher median Hp-IgG titer and lower level of B12; although not significant, this was still a clinical trend. Hp-IgG titer was negatively correlated with levels of FA (r = -0.601, P < .001) and B12 (r = -0.434, P < .001) and with the IIEF-5 score (r = -0.382, P < .001) and positively correlated with HCY (r = 0.69, P < .001). Clinical Implications: The ED group had higher levels of Hp-IgG titer and HCY and lower levels of B12 and FA. Strengths and Limitations: This study is the first to link Hp infection, FA, B12, and HCY and further explain the relationship between these indicators and the underlying pathologic mechanisms that jointly cause ED. The limitation is that our study was based on Hp-IgG titers, which do not necessarily represent the full extent of Hp infection, despite the avoidance of invasive testing. Conclusion: Hp infection might lead to decreased FA and B12 and then increased HCY, which might be a mechanism leading to ED. Hp eradication or FA and B12 supplementation might have certain clinical value in the treatment of vascular ED.

[Retracted] MicroRNA­143 inhibits cell migration and invasion by targeting matrix metalloproteinase 13 in prostate cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that several of the panels showing the results from cell migration and invasion assay experiments in Fig. 2 on p. 628 contained sections of data that were overlapping with other panels within the same figure. Given the issue of the overlapping sections of data, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of an overall lack of confidence in the presented results. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 8: 626­630, 2013; DOI: 10.3892/mmr.2013.1501].

microRNA-125b inhibits cell migration and invasion by targeting matrix metallopeptidase 13 in bladder cancer.

[This retracts the article DOI: 10.3892/ol.2013.1123.].

[Corrigendum] MicroRNA­335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in Fig. 3 on p. 4382, the 'Invasion' assay data for the negative control (NC) experiments for the T24 and EJ cell lines appeared to contain an overlap of data, such that they may have been derived from the same original source even though the data were purportedly intended to show the results from differently peformed experiments. The authors have re­examined their original data, and realize that this figure was inadvertently assembled incorrectly. The revised version of Fig. 3, showing alternative data from one of the repeated experiments, is shown below. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 4379-4385, 2016; DOI: 10.3892/mmr.2016.5055].

Long noncoding RNA NNT-AS1 enhances the malignant phenotype of bladder cancer by acting as a competing endogenous RNA on microRNA-496 thereby increasing HMGB1 expression.

The long noncoding RNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a key malignancy regulator in a variety of human cancers. In this study, we first measured the expression of NNT-AS1 in bladder cancer and examined its role in cancer progression. The mechanisms behind the oncogenic functions of NNT-AS1 in bladder cancer were explored. We found that NNT-AS1 was upregulated in bladder cancer tissues and cell lines. This increased expression demonstrated a significant correlation with advanced clinical stage, lymph node metastasis, and shorter overall survival. NNT-AS1 knockdown suppressed bladder cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro and hindered tumor growth in vivo. NNT-AS1 functioned as a competing endogenous RNA for microRNA-496 (miR-496), and the suppressive effects of NNT-AS1 knockdown on malignant characteristics were abrogated by miR-496 silencing. HMGB1 was identified as a direct target gene of miR-496 in bladder cancer, and HMGB1 expression was enhanced by NNT-AS1 via sponging of miR-496. In conclusion, the NNT-AS1-miR-496-HMGB1 pathway plays a significant role in the aggressive behavior of bladder cancer and may lead to new NNT-AS1-based diagnostics and therapeutics.

Clear Cell Renal Cell Carcinoma With Extensive Osseous Metaplasia: Report of a Rare Case.

A 48-year-old Chinese woman presenting with continuing dull pain in the right lower back and abdomen was found to have a tumor with extensive osseous metaplasia in the upper-middle pole of the right kidney. The excised neoplasm specimen revealed a 29 × 26 mm hard tumor with dense ossification. Histopathological examination of the tumor showed that it contained lamellar bone forming trabeculae intermingled and spherical or polygonal epithelial cells that contained slightly irregular nuclei with small nucleoli and abundant pink to clear cytoplasm. Clear cell renal cell carcinoma with extensive osseous metaplasia is a very rare occurrence.

Tumor-suppressing effects of microRNA-429 in human renal cell carcinoma via the downregulation of Sp1.

MicroRNA (miR)-429 has been frequently reported to be downregulated in various tumors, including renal cell carcinoma (RCC), nasopharyngeal carcinoma, Ehrlich ascites tumor cells, gastric cancer, non-small cell lung cancer and endometrial endometrioid carcinoma. The present study investigated the effects of miR-429 on human RCC A498 and 786-O cells. Following transfection of cells with miR-429 mimics and scrambled control, MTT, cell migration, cell invasion and luciferase assays were performed. In addition, western blotting was performed in order to assess the expression of specificity protein 1 (Sp1), which was predicted to be a target of miR-429 by TargetScan. The present results revealed that miR-429 inhibited cell proliferation, migration and invasion of 786-O and A498 cells. In addition, the present results demonstrated that miR-429 overexpression downregulated Sp1 protein expression, which provides evidence that miR-429 may directly target Sp1 in RCC. These results suggest that miR-429 may be investigated for use as a predictive marker for early detection of tumor metastasis and blocking RCC cells from becoming invasive.

MicroRNA-335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1.

The expression of microRNA­335 (miR­335) has been demonstrated to be downregulated in numerous types of cancer. Thus far, no previous studies have investigated the miR­335 expression in bladder cancer. In the present study, the expression and effects of miR­335 were assessed in bladder cancer. The results of the present study provided, to the best of our knowledge, the first evidence that miR­335 is downregulated in the tumor tissue of patients with bladder cancer. Following transfection of miR­335, MTT, cell migration and invasion, luciferase and western blot assays were conducted in bladder cancer cell lines. The results demonstrated that miR­335 inhibited cell proliferation, migration and invasion in T24 and EJ cells. In addition, the results suggested that miR­335 directly targets Rho­associated protein kinase 1 (ROCK1) in bladder cancer. The present study provided a novel therapeutic target, the miR­335/ROCK1 axis in bladder cancer. The suggested approach will be beneficial in developing an effective treatment against bladder cancer.

Novel somatic mutations identified by whole-exome sequencing in muscle-invasive transitional cell carcinoma of the bladder.

Transitional cell carcinoma (TCC) is the one of the most commonly observed types of cancer globally. The identification of novel disease-associated genes in TCC has had a significant effect on the diagnosis and treatment of bladder cancer; however, there may be a large number of novel genes that have not been identified. In the present study, the exomes of two individuals who were diagnosed with muscle-invasive TCC (MI-TCC) were sequenced to investigate potential variants. Subsequently, following algorithm and filter analysis, Sanger sequencing was used to validate the results of deep sequencing. Immunohistochemistry (IHC) was employed to observe the differences in HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) protein expression between tumor tissues and para-carcinoma tissues. A total of 6 nonsynonymous mutation genes were identified in MI-TCC, identified as copine VII, RNA binding motif protein, X-linked-like 3, acyl-CoA synthetase medium-chain family member 2A, HECW1, zinc finger protein 273 and trichohyalin. Furthermore, 5 cases were identified to possess a HECW1 gene mutation in 61 MI-TCC specimens, and all of these were point mutations located at exon 11 on chromosome 7. The mutation categories of HECW1 had 4 missense mutations and 1 nonsense mutation. IHC revealed that HECW1 protein was expressed at significantly increased levels in MI-TCC compared with normal bladder urothelium (P<0.001). The present study provided a novel approach for investigating genetic changes in the MI-TCC exome, and identified the novel mutant gene HECW1, which may possess a significant role in the pathogenesis of TCC.

MicroRNA-497 targets hepatoma-derived growth factor and suppresses human prostate cancer cell motility.

MicroRNA-497 (miR-497) has been reported to be downregulated in certain types of cancer, including breast, gastric, endometrial, colorectal and prostate cancer as well as hepatocellular and nasopharyngeal carcinoma. The present study aimed to investigate the underlying mechanism of the tumor suppressor function of miR­497 in prostate cancer. Following transfection with miR­497, the DU145 and PC­3 prostate cancer cell lines were subjected to Transwell migration and invasion assays, western blot analysis and a luciferase assay. It was revealed that miRNA­497 inhibited the migration and invasion of prostate cancer cells. In addition, is was indicated that miRNA­497 directly targets hepatoma­derived growth factor (HDGF) in prostate cancer cells. These results suggested that restoration of miR­497 and the resulting downregulation of HDFG may represent a promising therapeutic strategy for prostate cancer.

Upregulation of microRNA-204 inhibits cell proliferation, migration and invasion in human renal cell carcinoma cells by downregulating SOX4.

MicroRNA-204 (miR-204) has been reported to be frequently downregulated in various types of cancer, including renal, brain, ovary, hematological and colon cancer. The present study, investigated the effects of miR­204 on renal cell carcinoma. Following transfection of miR­204, an MTT assay, cell migration assay, cell invasion assay, western blot analysis and luciferase assay were performed in renal cell carcinoma cell lines. It was demonstrated that miR­204 inhibits cell proliferation, migration and invasion in 786­O and A498 cells. To the best of our knowledge, this study is the first to demonstrate that miR­204 directly targets SOX4 in renal cell carcinoma. These results suggested that miR-204 may have value as a marker for the early detection of tumor metastasis and a therapeutic target preventing the invasion of renal cell carcinoma.

Upregulation of the B7/CD28 family member B7-H3 in bladder cancer.

Dysregulation of B7-H3 has been observed in a variety of types of human cancers. In the present study, the mRNA expression level of B7-H3 was analyzed in bladder cancer by performing semi-quantitative reverse transcription-polymerase chain reaction on clinical specimens from transitional cell carcinomas (TCCs) and their normal adjacent tissues (NATs). Immunohistochemical analysis was performed to compare the protein expression level of B7-H3 in TCCs and the paired NATs. The present study indicated that the B7-H3 mRNA expression level was significantly higher in the TCC samples compared with the paired NAT samples. Furthermore, immunohistochemical analyses indicated that the B7-H3 protein expression level was significantly upregulated in the TCC samples compared with in the paired NAT samples, indicating that B7-H3 dysregulation may be important in the progression of bladder cancer.

microRNA­99a inhibits cell proliferation, colony formation ability, migration and invasion by targeting fibroblast growth factor receptor 3 in prostate cancer.

microRNA­99a (miR­99a) was reported to be among the most frequently downregulated miRNAs in numerous types of human cancers, including prostate, bladder, hepatocellular and ovarian carcinoma, squamous cell carcinoma of the tongue, squamous cell lung carcinoma as well as childhood adrenocortical tumors. The aim of the present study was to determine the effects of miRNA­99a on cell proliferation, colony formation ability, migration and invasion in prostate cancer. Following transfection with miRNA­99a, cell viability, colony formation, cell migration and cell invasion assays were performed on prostate cancer cell lines, as well as western blot analysis and luciferase assays. miRNA­99a inhibited cell proliferation, colony formation ability, migration and invasion in DU145 and PC­3 cells, therefore indicating that miRNA­99a may have a tumor suppressive role in prostate cancer. In addition, the present study provided the first evidence that the mechanism of action of miRNA­99a may proceed by directly targeting fibroblast growth factor receptor 3 in prostate cancer. In conclusion, the results of the present study suggested that miRNA­99a may have potential use as a therapeutic target for the treatment of prostate cancer.

microRNA-99a inhibiting cell proliferation, migration and invasion by targeting fibroblast growth factor receptor 3 in bladder cancer.

The expression of microRNA-99a (miRNA-99a) has been investigated in a number of human cancers. It has been reported to be downregulated in several types of cancer, including ovarian carcinoma, squamous cell carcinoma of the tongue, squamous cell lung carcinoma, hepatocellular carcinoma, bladder cancer, prostate cancer and childhood adrenocortical tumors. In the present study, the effects of miRNA-99a on bladder cancer cell proliferation, migration and invasion were examined. Following transfection of miRNA-99a, cell viability, cell migration assay, cell invasion, western blot analysis and luciferase assays were conducted in bladder cancer cell lines. It was found that miRNA-99a inhibits cell proliferation, migration and invasion in T24 and EJ cells. Additionally, this study provided the first evidence that miRNA-99a is likely to directly target fibroblast growth factor receptor 3 in bladder cancer. The study provided evidence that miRNA-99a suppresses cell proliferation, migration and invasion by targeting growth factor receptor 3 in bladder cancer cell lines. These results indicated that it could be investigated as a target for therapeutic drugs designed to treat bladder cancer.

microRNA­145 inhibits cell proliferation, migration and invasion by targeting matrix metallopeptidase-11 in renal cell carcinoma.

microRNA­145 (miR­145) has been reported to be frequently downregulated in various types of cancer, including renal, prostate, bladder, lung and colon cancer, as well as B­cell malignancies. The present study examined the effects of miR­145 on the cell proliferation, migration and invasion of renal cell carcinoma (RCC). Following transfection of miR­145, an MTT, cell migration, cell invasion and luciferase assays, and western blot analysis were conducted in RCC cell lines. The present study demonstrated that miR­145 inhibited cell proliferation, migration and invasion in 786­O and A498 cells. The present study also demonstrated for the first time, to the best of our knowledge, that miR­145 may directly target matrix metallopeptidase­11 (MMP­11) in RCC. miR­145 was demonstrated to suppress cell proliferation, migration and invasion by targeting MMP­11 in RCC cell lines. These results suggested that it may be investigated as a predictive marker for the early detection of tumor metastasis and for targeting therapeutic drugs to inhibit the invasion of RCC.

microRNA-133b downregulation and inhibition of cell proliferation, migration and invasion by targeting matrix metallopeptidase-9 in renal cell carcinoma.

microRNA (miRNA)-133b has been revealed to be downregulated in head and neck/oral, bladder, human non-small cell lung, colorectal and esophageal squamous cell cancer. The present study examined the expression of miR-133b in renal cell carcinoma (RCC) cell lines and the effects of miRNA-133b on RCC cell proliferation, migration and invasion. Quantitative polymerase chain reaction was used to detect the expression of miR-133b in RCC cell lines. Following transfection of miR-133b, the expression of miR-133b was examined and a cell viability assay, cell migration assay, cell invasion assay, western blot analysis and luciferase assay were conducted in RCC cell lines. The present study revealed that miRNA­133b was downregulated and inhibited cell proliferation, migration and invasion in 786-O and A498 cells. In addition, to the best of our knowledge, the present study provided the first evidence that miRNA-133b may directly target matrix metallopeptidase 9 (MMP-9) in RCC. The present study also provided evidence that miRNA-133b suppresses cell proliferation, migration and invasion by targeting MMP-9 in RCC cell lines. These results suggested that miRNA-133b may be used for the development of novel molecular markers and therapeutic approaches to inhibit the metastasis of RCC.

MicroRNA-143 inhibits cell migration and invasion by targeting matrix metalloproteinase 13 in prostate cancer.

MicroRN-143 (miR­143) has been previously reported to be downregulated in specific types of cancer, including colorectal, bladder, oral squamous cell, pituitary, cervical, nasopharyngeal, lymphoma and prostate cancer. In the present study, the effects of miR-143 on prostate cancer cell migration and invasion were examined. Following transfection with miR-143, miR-143 expression, cell migration and invasion assays, luciferase assay and western blot analysis were conducted in prostate cancer cell lines. The results indicated that miR-143 inhibits cell migration and invasion in DU145 and PC-3 cells. In addition, to the best of our knowledge, miR-143 was reported for the first time to directly target matrix metalloproteinase 13 (MMP-13) in prostate cancer. The results of the present study demonstrated that miR-143 suppresses cell migration and invasion by targeting MMP-13 in prostate cancer cell lines. These results indicated that miR-143 may be suitable for the development of novel molecular markers and therapeutic approaches to inhibit metastasis in prostate cancer.

microRNA-125b inhibits cell migration and invasion by targeting matrix metallopeptidase 13 in bladder cancer.

The expression of microRNA-125b (miR-125b) has been investigated in many human cancers. It has been demonstrated to be downregulated in certain types of cancer, such as bladder cancer, thyroid anaplastic carcinomas, squamous cell carcinoma of the tongue, hepatocellular carcinoma, ovarian and breast cancer. In the present study, we examined the effects of miR-125b on bladder cancer cell migration and invasion. Following transfection of miR-125b, the expression of miR-125b was analyzed in T24 and EJ bladder cancer cells. Additionally, cell migration, cell invasion and luciferase assays, as well as western blot analysis were conducted in the bladder cancer cells. In this study, we demonstrated that miR-125b inhibited cell migration and invasion in T24 and EJ cells. We also provided the first evidence that miR-125b may directly target matrix metalloproteinase 13 (MMP13) in bladder cancer. Our study provided evidence that miR-125b suppresses cell migration and invasion by targeting MMP13 in bladder cancer cell lines. These results suggested that miR-125b could be used for the development of new molecular markers and therapeutic approaches to inhibit bladder cancer metastasis.