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BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.
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Membranas Asociadas a Mitocondrias , Daño por Reperfusión , Humanos , Fosfatidilinositol 3-Quinasas , Proteómica , HipoxiaRESUMEN
Objective: To investigate the therapeutic effect of apocynin on oligoasthenozoospermia (OAS) and its action mechanisms in mice. METHODS: Forty male Kunming mice were randomly divided into four groups of equal number, blank control, OAS model, low-dose apocynin, and high-dose apocynin. OAS models were made in the latter three groups of mice by intraperitoneal injection of cyclophosphamide for five days. The animals in the blank control, OAS model, low-dose apocynin, and high-dose apocynin groups were given drinking water (ï¼»5.1±0.4ï¼½ ml daily) containing 0, 0, 200, and 1 000 µg/ml apocynin, respectively, for 30 days. Then all the mice were sacrificed for observation of pathological changes of the testicular tissue, examination of sperm quality, and measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the testis. RESULTS: Apocynin treatment raised sperm concentration from (2.94±0.57)×106/ml in the OAS models to (3.88±0.43) and (4.12±0.53)×106/ml in the low- and high-dose apocynin groups and elevated the percentage of progressively motile sperm from (6.25±3.40)% in the OAS models to (8.03±6.71) and (17.50±2.74)% in the low- and high-dose apocynin groups, respectively (P<0.05). The MDA level in the testicular tissue was decreased from (1.34±0.22) nmol/mg prot in the OAS models to (1.13±0.19) and (0.98±0.19) nmol/mg prot in the low- and high-dose apocynin groups (P<0.05), and the SOD level increased from (26.46±4.36) U/mg prot to (32.46±3.28) and (37.39±5.77) U/mg prot, respectively (P<0.05). CONCLUSIONS: Apocynin can significantly improve sperm quality of oligoasthenozoospermia mice by eliminating reactive oxygen free radicals and improving antioxidant activity of the body. And it can be applied in the prevention and treatment of male infertility.
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Acetofenonas/farmacología , Antioxidantes/farmacología , Astenozoospermia/tratamiento farmacológico , Animales , Medicamentos Herbarios Chinos , Masculino , Malondialdehído/metabolismo , Ratones , Especies Reactivas de Oxígeno/metabolismo , Recuento de Espermatozoides , Espermatozoides , Superóxido Dismutasa/metabolismo , Testículo/metabolismoRESUMEN
BACKGROUND: The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. METHODS: We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t-test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients' clinical characteristics was assessed by univariate analysis. RESULTS: In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients' prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients' gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. CONCLUSION: The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.
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Linfocitos B/inmunología , Neoplasias Gástricas/inmunología , Linfocitos T Reguladores/inmunología , Microambiente Tumoral/inmunología , Femenino , Factores de Transcripción Forkhead/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patologíaRESUMEN
PURPOSE: Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are complex diseases affected by both dietary intake and genetic background. Whether N-5, 10-methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, high-sensitivity C-reactive protein (hs-CRP) and dietary components folate and vitamin B12 are associated with MS in Asian has not been determined. METHODS: We hypothesized that MTHFR gene C677T, folate, vitamin B12 and hs-CRP are associated with MS and factors related to MS in northern Han Chinese. To test this hypothesis, MTHFR C677T gene polymorphism was determined by PCR-RFLP, serum insulin, folate and vitamin B12 levels by radioimmunoassay, and hs-CRP by immunoturbidimetry in newly diagnosed T2DM patients with MS (118) and without MS (40), and in 55 healthy subjects. RESULTS: Results indicated that MS-associated T2DM accounts for 75% of newly diagnosed T2DM in Han Chinese. Serum hs-CRP was higher and serum vitamin B12 was lower in subjects with TT genotype in comparison with those with CC or CT genotypes. Total T frequency was significantly higher in MS-associated T2DM patients (45.3%) compared to 26.3% in non-MS-associated T2DM patients. MTHFR C677T gene polymorphism and vitamin B12 levels were associated with MS-associated T2DM. CONCLUSION: MTHFR C677T gene polymorphism may contribute to insulin resistance in Han Chinese with MS by increasing hs-CRP and decreasing vitamin B12, and consequently play an important role in development of MS-associated T2DM.
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Proteína C-Reactiva/metabolismo , Predisposición Genética a la Enfermedad/genética , Resistencia a la Insulina/genética , Síndrome Metabólico/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético/genética , Vitamina B 12/sangre , Anciano , Pueblo Asiatico , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Persona de Mediana Edad , RadioinmunoensayoRESUMEN
AIM: To construct urothelium-specific recombinant adenovirus and investigate its inhibition in bladder cancer cell. METHODS: RT-PCR analysis was used to determine expression patterns of hUPII and coxsackie adenovirus receptor on multiple cell lines. Transient transfection and luciferase detecting assay were used to detect tissue specificity of the hUPII promoter. Recombinant adenovirus Ad-UPII-E1A and Ad-UPII-Null were constructed. Restrictive enzyme digestion assay and PCR confirmed the correct construction. The adenovirus E1A protein expressed in BIU-87 was tested by Western blot after cells were infected with recombinant adenovirus. Recombinant adenovirus Ad-UPII-E1A was tested for its inhibition in bladder cancer cell line BIU-87. RESULTS: HUPII and CAR were expressed and the hUPII promoter is highly active in bladder cancer cell line BIU-87. Using homologous recombination in bacteria technology, the hUPII promoter and E1A gene were inserted into the genome of type 5 recombinant adenovirus. The E1A protein was markedly positive in the samples of BIU-87 cells infected with recombinant adenovirus Ad-UPII-E1A. MTT assay demonstrated recombinant adenovirus Ad-UPII-E1A inhibited bladder cancer cell BIU-87 growth. CONCLUSION: The hUPII promoter shows high tissue specificity. Recombinant adenovirus Ad-UPII-E1A and Ad-UPII-Null were constructed and confirmed. Recombinant adenovirus Ad-UPII-E1A is effective in inhibition in bladder cancer cell line BIU-87.
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Adenoviridae/genética , Proteínas E1A de Adenovirus/metabolismo , Terapia Genética/métodos , Vectores Genéticos , Proteínas de la Membrana/metabolismo , Regiones Promotoras Genéticas , Receptores Virales/metabolismo , Transfección , Neoplasias de la Vejiga Urinaria/metabolismo , Urotelio/metabolismo , Proteínas E1A de Adenovirus/genética , Línea Celular Tumoral , Supervivencia Celular , Proteína de la Membrana Similar al Receptor de Coxsackie y Adenovirus , Humanos , Proteínas de la Membrana/genética , Receptores Virales/genética , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/terapia , Uroplaquina II , Urotelio/patologíaRESUMEN
Background. Several factors have been validated as predictors of disease recurrence in upper tract urothelial carcinoma. However, the oncological outcomes between different surgical approaches (open nephroureterectomy versus laparoscopic nephroureterectomy, ONU vs LNU) remain controversial. Therefore, we performed a meta-analysis to evaluate the oncological outcomes associated with different surgical approaches. Methods. We conducted an electronic search of the PubMed, Embase, ISI Web of Knowledge and Cochrane Library electronic databases through November 2015, screened the retrieved references, collected and evaluated the relevant information. We extracted and synthesized the corresponding hazard ratios (HRs) and 95% confidence intervals (95% CI) using Stata 13. Results. Twenty-one observational studies were eligible for inclusion in the meta-analysis. The results of the meta-analysis showed no differences in the intravesical recurrence-free survival (IRFS), unspecified recurrence-free survival (UnRFS) and overall survival (OS) between LNUandONU. However, improvements in the extravesical recurrence free survival (ExRFS) and cancer specific survival (CSS) were observed inLNU. The pooled hazard ratios were 1.05 (95% CI [0.92-1.18]) for IRFS, 0.80 (95% CI [0.64-0.96]) for ExRFS, 1.10 (95% CI [0.93-1.28]) for UnRFS, 0.91 (95% CI [0.66-1.17]) for OS and 0.79 (95% CI [0.68-0.91]) for CSS. Conclusion. Based on current evidence, LNU could provide equivalent prognostic effects for upper tract urothelial carcinoma, and had better oncological control of ExRFS and CSS compared to ONU. However, considering all eligible studies with the intrinsic bias of retrospective study design, the results should be interpreted with caution. Prospective randomized trials are needed to verify these results.
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BACKGROUND: Laparoscopic renal surgery has been widely used in the treatment of renal diseases. However, there is still little research about its application in addressing renal tuberculosis. The purpose of this study is to retrospectively investigate the surgical results of laparoscopic and open surgery for nonfunctional tuberculous kidneys. METHODS: Between May 2011 and June 2016, 120 nephrectomies were performed in patients with a nonfunctional tuberculous kidney. Of these, 69 patients underwent retroperitoneal laparoscopic nephrectomy, and 51 patients underwent open nephrectomy. Data about the patients' characteristics and surgical outcomes were collected from their electronic medical records. Outcomes were compared between these two groups. RESULTS: Our results showed that a number of renal tuberculosis patients presented no significant symptoms during their disease. Lower urinary tract symptoms (LUTS) were the most common at a rate of 73/120, followed by flank pain or accidently discovery (66/120), urine abnormality (30/120) and fever (27/120). Patients who underwent open surgery were similar to laparoscopic patients with regard to sex, BMI, location, previous tuberculous history, grade, anemia, adhesion, hypertension, diabetes and preoperative serum creatinine level, but were generally older than laparoscopic patients. There were no significant differences between open and laparoscopic surgery in estimated blood loss, transfusion, postoperative hospital days and perioperative complication rate. However, the median operation time of laparoscopic operation was much longer than open surgery (180 [150-225] vs 135 [120-165] minutes, P < 0.01). Seven of the 69 laparoscopic operations were converted to open surgery because of severe adhesions. CONCLUSION: Laparoscopic nephrectomy is as an effective treatment as open surgery for a nonfunctional tuberculous kidney, although it requires more time during the surgical procedure. No significant differences in other surgical outcomes were observed.
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The relationship between inflammation and tumor development and progression has been recognized in recent decades. NLR is an easily reproducible and widely used inflammatory response marker. The prognostic value of NLR for urologic tumors has been reported in succession. Here, we perform a systematic review and meta-analysis to summarize the association between the NLR and prognosis of urologic tumors. We conducted a computerized search of PubMed, Embase, and ISI Web of Knowledge to identify clinical studies that had evaluated the association between the pretreatment NLR and prognosis in urologic tumors. Prognostic outcomes included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and metastasis-free survival (MFS). We extracted and synthesized corresponding hazard ratios (HRs) and confidence intervals (CIs) using Review Manager 5.3 and STATA 13. We identified 34 retrospective cohort studies and conducted the meta-analysis. The results showed that all OS, CSS, RFS, PFS, and MFS risks were significantly different between patients with an elevated NLR and those with a low NLR in various urologic tumors. A high NLR portended poor prognosis. However, no significance was observed for CSS in patients with renal cell carcinoma (HR = 1.38, 95% CI: 0.96-1.99). Our meta-analysis suggests that NLR could be a prognostic predictor for urologic tumors. Patients with a high NLR were deemed to have a poor prognosis.
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Linfocitos/citología , Neutrófilos/citología , Neoplasias Urológicas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Estudios de Cohortes , Humanos , Recuento de Leucocitos , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Upper tract urothelial carcinoma (UTUC) is a relatively rare and highly aggressive tumor. However, the prognosis of UTUC is rarely predicted accurately due to the lack of reliable biomarkers. C-reactive protein (CRP) has been found to be correlated with several types of cancer. In this study, we performed a systematic review and meta-analysis to determine the association between CRP levels and prognosis in UTUC. A computerized search was conducted through PubMed, Embase, Web of Science, the Cochrane Library and CBM databases to identify clinical studies that have evaluated the association between preoperative CRP levels and prognosis of UTUC. The prognostic outcomes included recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). We extracted and synthesized corresponding hazard ratios (HRs) and confidence intervals (CIs) using Review Manager 5.3 software. We identified 7 retrospective cohort studies including a total of 1,919 patients and analyzed these studies using univariate and multivariate models. Our meta-analysis results revealed that RFS and CSS were significantly different between patients with elevated CRP levels and those with low CRP levels (P<0.0001 and P<0.00001, respectively); however, that was not the case for OS (P=0.22) in the multivariate or the univariate model. The pooled HR of RFS was 2.90 (95% CI: 1.87-4.51, P<0.00001) in the univariate analysis and 1.57 (95% CI: 1.26-1.97, P<0.0001) in the multivariate analysis. The pooled HRs of CSS were 2.78 (95% CI: 1.75-4.43, P<0.0001) and 1.64 (95% CI: 1.32-2.03, P<0.00001) in the univariate and multivariate analysis, respectively. However, the pooled HRs of OS were not significant in the univariate [1.24 (95% CI: 0.72-2.15, P=0.43)] or the multivariate analysis [1.24 (95% CI: 0.88-1.75, P=0.22)]. In conclusion, our meta-analysis results suggested that CRP level may be a prognostic predictor in UTUC.
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Recent studies suggest that statin may benefit cancer prognosis, especially through its radiosensitization effect. But controversy exists in other studies. Hence, we performed a meta-analysis of results from 35 studies to evaluate the effect of statin use on urologic cancers.We conducted computerized search from PubMed, Embase, and ISI Web of Knowledge through May 2015, screened the retrieved references, and collected and evaluated relevant information. We extracted and synthesized corresponding hazard ratios (HR) and confidence interval (CI) by using Review Manager 5.3 and STATA 13. This review was registered at PROSPERO with registration No. CRD42015020171.We selected total 35 retrospective studies and conducted a meta-analysis of results from these studies. The pooled results suggested no benefit of statin use to bladder cancer and renal cell carcinoma, except overall survival [HRâ=â0.81, 95% CI: 0.69-0.96]. However, significant improvement of prostate cancer prognosis including overall survival [HRâ=â0.82, 95% CI: 0.70-0.97] and cancer-specific survival [HRâ=â0.70, 95% CI: 0.59-0.83] was indicated, but not including tumor progression [HRâ=â0.84, 95% CI: 0.62-1.14]. Statin use improved biochemical recurrence of prostate cancer in radiotherapy patients [HRâ=â0.68, 95% CI: 0.54-0.85] but not in radical prostatectomy patients [HRâ=â0.97, 95% CI: 0.82-1.15].Current evidence suggests no benefit of statin use to bladder cancer and renal cell carcinoma, except in overall survival. While statin use benefited prostate cancer patients in overall survival, cancer-specific survival but not in tumor progression; it also improved biochemical recurrence in radiotherapy patients but not in radical patients. To verify these results, randomized controlled trials are necessary.
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Carcinoma de Células Renales/diagnóstico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Carcinoma de Células Renales/terapia , Progresión de la Enfermedad , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Vejiga Urinaria/terapiaRESUMEN
PURPOSE: To evaluate and update evidence for prognostic effects of kidney-sparing (KS) management and nephroureterectomy (NU) for upper tract urothelial carcinomas. MATERIALS AND METHODS: Pubmed, Embase and the Cochrane Library were retrieved for the identification of comparative studies of kidney-sparing procedure and nephroureterectomy for upper tract urothelial carcinoma prior to December 2014. The data were extracted independently by 2 reviewers and the quality of the included studies was assessed. Review Manager 5.3 and STATA 13 were used to perform the meta-analysis. RESULTS: Twenty-three observational studies including 1,587 KS and 3,996 NU were evaluated. The results of the meta-analysis showed that nephroureterectomy had no significant benefit with regard to intravesical recurrence (IRFS), metastasis (MFS), cancer specific survival (CSS) and overall survival (OS) except the total tumor recurrence (RFS) when compared with kidney sparing management. The respectively pooled outcomes were HR 1.36 (0.69-2.68, P=0.38) for IRFS, 1.09 (0.59-2.01, P=0.78) for MFS, 1.17 (0.77-1.79, P=0.47) for CSS, 1.50 (0.90-2.48, P=0.12) for OS and 1.61 (1.03-2.51, P=0.04) for RFS. CONCLUSIONS: On the whole, kidney-sparing management had equivalent prognostic effect on upper tract urothelial carcinoma as the standard nephroureterectomy except in tumor recurrence. However, the results should be interpreted with caution for lack of stage and grade stratification and multi-center randomized controlled trials are still needed to verify our results.
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Neoplasias Renales/cirugía , Nefrectomía , Tratamientos Conservadores del Órgano , Uréter/cirugía , Neoplasias Ureterales/cirugía , Manejo de la Enfermedad , Humanos , Neoplasias Renales/patología , Pronóstico , Neoplasias Ureterales/patologíaRESUMEN
OBJECTIVE: To evaluate the value of liquid-based cytology (LBC) in the diagnosis of urothelial carcinoma. METHOD: Diagnostic studies were searched for the diagnostic value of LBC in urothelial carcinoma in PubMed, Embase, Cochrane Library, Web of Science, CBM and CNKI. The latest retrieval date was September 2014. The data were extracted and the quality of the included studies was independently assessed by 2 reviewers. Stata 13 software was used to perform the statistical analysis. The research was conducted in compliance with the PRISMA statement. RESULT: Nineteen studies, which included 8293 patients, were evaluated. The results of the meta-analysis showed that the pooled sensitivity and specificity of LBC were 0.58 (0.51-0.65) and 0.96 (0.93-0.98), respectively. The diagnostic odds ratio (DOR) was 31 (18-56) and the area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.83 (0.80-0.86). The post-test probability was 80% when a positive diagnosis was made. Compared with high grade urothelial carcinoma (HGUC), the sensitivity of detecting low-grade urothelial carcinoma (LGUC) was significantly lower, risk ratio of sensitivity was 0.54 (0.43-0.66), P<0.001. However, no significant sensitivity improvement was observed with LBC when compared with traditional cytospin cytology, risk ratio was 1.03 (0.94-1.14), P = 0.524. CONCLUSION: Despite LBC having a pooled 58% positive rate for urothelial carcinoma diagnosis in our meta-analysis, no significant improvement in sensitivity was observed based on the studies evaluated. Further research is needed to validate these findings.
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Carcinoma de Células Transicionales/diagnóstico , Técnicas Citológicas , Orina/citología , Neoplasias Urológicas/diagnóstico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/orina , Centrifugación , Humanos , Oportunidad Relativa , Proyectos de Investigación , Sensibilidad y Especificidad , Soluciones , Coloración y Etiquetado , Neoplasias Urológicas/patología , Neoplasias Urológicas/orinaRESUMEN
We wished to evaluate the effects of Pseudomonas aeruginosa (mannose-sensitive hemagglutination pilus strain, PA-MSHA) as an immunostimulating and anti-tumor agent for treatment of bladder cancer. Immunostimulating effects were assessed by the in vitro proliferation assay of murine splenic lymphocytes. Anti-tumor effects were studied in a subcutaneous tumor model established in female C57BL/6 mice using the MB49 bladder cell line. These mice received subcutaneous injections of normal saline (control group) or PA-MSHA (high, medium, or low dose, respectively, 1.6-2.0 × 10(9), 3.2- .0 × 10(8), 6.4-8.0 × 10(7) CFU/ml) twice a week for 3 weeks. Mice survival, tumor volume, vascular endothelial growth factor (VEGF) expression, microvessel density (MVD), serum levels of TNF-α and IFN-γ, and blood CD4(+) /CD8(+) counts were the study outcomes. We observed that PA-MSHA promoted the growth of splenic lymphocytes in vitro. In the murine tumor model, PA-MSHA prolonged mice survival and reduced tumor growth. Furthermore, VEGF and MVD were also diminished by PA-MSHA. Mice that received high and medium dose of PA-MSHA had significantly higher serum levels of IFN-γ and TNF-α (days 21 and 28), and higher levels of CD4(+) /CD8(+) cells (days 21 and 28). In conclusion, PA-MSHA exerts beneficial effects on increasing proliferation of murine splenic lymphocytes in vitro and inhibits the growth of bladder tumor in a murine model. Therefore, PA-MSHA may be useful an immunostimulating and anti-tumor agent for bladder cancer therapy.
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Proteínas Fimbrias/uso terapéutico , Inmunoterapia , Linfocitos/inmunología , Pseudomonas aeruginosa/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Animales , Relación CD4-CD8 , Línea Celular Tumoral , Proliferación Celular , Células Cultivadas , Femenino , Proteínas Fimbrias/inmunología , Interferón gamma/sangre , Linfocitos/fisiología , Ratones , Ratones Endogámicos C57BL , Neovascularización Patológica/terapia , Bazo/citología , Factor de Necrosis Tumoral alfa/sangre , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
This systematic review was conducted to assess the efficacy and safety of bisphosphonates for prevention and treatment of osteopenia or osteoporosis in men with non-metastatic prostate cancer receiving androgen- deprivation therapy. We searched for randomised controlled trials (RCTs) of bisphosphonates compared with placebo from Pubmed, Embase, the Cochrane Library, and ISI - Science Citation Index. Meta-analyses of pre- specified outcomes (bone mineral density, fractures, and adverse events) were performed using Review Manager. Ten RCTs with a total patient population of 1,017 were identified. There was generally more improvement in bone mineral density of the lumbar spine for patients who received bisphosphonate treatment than placebo or other medical treatment at 12 months (WMD 6.02,95%CI 5.39 to 6.65). Similar effects were also observed for total hip, trochanter or femoral neck bone mineral density. However, there was no significant reduction in fractures. Fever and gastrointestinal symptoms were the most common adverse events (10.4% vs. 1.2%; 0.10% vs. 0.03%). Currently, our meta-analysis suggested that oral and intravenous bisphosphonates caused a rapid increase in spine and hip or femoral BMD in non-metastatic prostate cancer patients receiving androgen-deprivation therapy. Fever and gastrointestinal symptoms were common with the use of bisphosphonates. These short-term trials (maximum of 12 months) did not show fracture reduction. In future, more efficient performance of higher quality, more rigorous, large sample, long-term randomised controlled trials (>12 months) are needed where outcomes are detailed.
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Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/uso terapéutico , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Enfermedades Óseas Metabólicas/prevención & control , Fémur/fisiología , Fracturas Óseas/epidemiología , Fracturas Óseas/patología , Cadera/fisiología , Humanos , Vértebras Lumbares/fisiología , Masculino , Osteoporosis/prevención & control , Neoplasias de la Próstata/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Carcinoma Hepatocelular/patología , Inhibidores de la Ciclooxigenasa 2/farmacología , Neoplasias Hepáticas/patología , Nitrobencenos/farmacología , Sulfonamidas/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Células Tumorales CultivadasRESUMEN
AIM: To determine the drug action mechanism of pollen extract EA-10, P5 on the treatment of chronic prostatitis (CP) or infertility with CP. METHODS: Malondiadehyde (MDA), superoxide dismutase (SOD), and nitrogen monoxide (NO) were measured by biochemical assay, and zinc content was assayed by atomical spectrophotography in the pre-treatment and post-treatment of CP or infertility with CP. RESULTS: Compared with control group, leukocytes in expressed protatic secretion (LEPS), MDA, and NO were increased, and zinc content and SOD were decreased significantly in the pre-treatment of CP. After the treatment, LEPS was improved, and MDA and NO were reduced, while zinc content were increased apparently and the alteration of SOD was not evident (P>0.05). In the pre-treatment of infertility with CP, LEPS, MDA, NO, sperm viability, and seminal leukocytes were obviously higher and seminal plasma SOD, zinc content, and sperm motility were obviously lower than those in control group. After the treatment, LEPS, sperm motility, and sperm viability were improved, MDA, NO, and seminal leukocytes were decreased, SOD and zinc content were increased markedly. CONCLUSION: There was inter-correlation between oxygen free radicals (OFR) and occurrence, development, and recovery of CP; Change of OFR may be involved in the drug action mechanism of EA-10, P5 in the treatment of CP or infertility with CP.