Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
Biomedicines ; 9(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34829899

RESUMO

BACKGROUND: Erectile dysfunction (ED) remains an emotional wrench to patients and a therapeutic challenge to urologists in andrology clinics worldwide. This is, in part, related to refraction to, or transient effect of phosphodiesterase 5 inhibitors (PDE5i), coupled with patients' dissatisfaction with this treatment modality. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is an evolving treatment option, with promising curative potential. Current international guidelines are inconclusive, bear weak recommendation strength, and lack ethnogeographic consensus. OBJECTIVES: This study evaluated the safety, efficacy, and effect duration of Li-ESWT, as well as exploring disease-associated determinants of treatment success in Taiwanese males with ED. METHODS: A cohort of 69 eligible cases treated with 12 sessions of Li-ESWT and followed up for at least 12 months after treatment, between January 2018 and December 2019 at our medical facility, was used. The present single-center, retrospective, non-randomized, single-arm study employed standardized erectile function evaluation indices, namely, the five-item International Index of Erectile Function (IIEF-5) and Erection Hardness Score (EHS). Clinicopathological analyses of selected variables and comparative analyses of time-phased changes in the EF indices relative to baseline values were performed. Evaluation of treatment success was based on minimal clinically important difference (MCID), using a binomial logistic regression model. RESULTS: The median age and duration of ED for our Taiwanese cohort were 55 years and 12 months, respectively, and an average of 31.3% presented with co-morbidities. The mean improvement in IIEF-5, EHS, and quality of life (QoL) domain scores relative to the baseline values was statistically very significant (p < 0.001) at all indicated follow-up time-points. When stratified, Taiwanese patients with severe and moderate ED benefited more from Li-ESWT, compared with those in the mild or mild-to-moderate group. Patients' pre-Li-ESWT PDE5i response status was not found to significantly influence Li-ESWT response. Univariate analysis showed that age > 45 years (p = 0.04), uncontrolled diabetes mellitus (p = 0.04), and uncontrolled hyperlipidemia (p = 0.01) were strongly associated with Li-ESWT efficacy; however, only age > 45 years (p = 0.04) and uncontrolled hyperlipidemia (p = 0.03) were found to be independent negative predictors of Li-ESWT success by the multivariate logistic model. Follow-up was uneventful, with no treatment-related adverse events or side effects reported. Of the treated patients, 86.1% indicated satisfaction with the treatment regimen, and over 90% indicated they would recommend the same therapy to others. CONCLUSIONS: Li-ESWT is a safe and efficacious therapeutic modality for Taiwanese patients with ED. Uncontrolled hyperlipidemia and age > 45 years are independent negative predictors of treatment success for this cohort.

2.
J Chin Med Assoc ; 84(11): 1028-1037, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596082

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect countries worldwide. To inhibit the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), testing of patients, contact tracing, and quarantine of their close contacts have been used as major nonpharmaceutical interventions. The advantages of antigen tests, such as low cost and rapid turnaround, may allow for the rapid identification of larger numbers of infectious persons. This meta-analysis aimed to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. METHODS: We searched PubMed, Embase, Cochrane Library, and Biomed Central databases from inception to January 2, 2021. Studies evaluating the diagnostic accuracy of antigen testing for SARS-CoV-2 with reference standards were included. We included studies that provided sufficient data to construct a 2 × 2 table on a per-patient basis. Only articles in English were reviewed. Summary sensitivity and specificity for antigen tests were generated using a random-effects model. RESULTS: Fourteen studies with 8624 participants were included. The meta-analysis for antigen testing generated a pooled sensitivity of 79% (95% CI, 66%-88%; 14 studies, 8624 patients) and a pooled specificity of 100% (95% CI, 99%-100%; 14 studies, 8624 patients). The subgroup analysis of studies that reported specimen collection within 7 days after symptom onset showed a pooled sensitivity of 95% (95% CI, 78%-99%; four studies, 1342 patients) and pooled specificity of 100% (95% CI, 97%-100%; four studies, 1342 patients). Regarding the applicability, the patient selection, index tests, and reference standards of studies in our meta-analysis matched the review title. CONCLUSION: Antigen tests have moderate sensitivity and high specificity for the detection of SARS-CoV-2. Antigen tests might have a higher sensitivity in detecting SARS-CoV-2 within 7 days after symptom onset. Based on our findings, antigen testing might be an effective method for identifying contagious individuals to block SARS-CoV-2 transmission.


Assuntos
Antígenos Virais/análise , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Humanos , Sensibilidade e Especificidade
3.
Front Oncol ; 11: 731460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671556

RESUMO

Purpose: This study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy. Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches. Results: Among the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p <0.001). Conclusions: Minimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.

4.
Surg Endosc ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716480

RESUMO

PURPOSE: Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear. METHODS: We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment. RESULTS: The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively). CONCLUSIONS: The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.

5.
Sci Rep ; 11(1): 19059, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561545

RESUMO

Tumor multifocality and location are prognostic factors for upper tract urothelial carcinoma (UTUC). However, confounding effects can appear when these two factors are analyzed together. Therefore, we aimed to investigate the impact of tumor distribution on the outcomes of multifocal UTUC after radical nephroureterectomy. From the 2780 UTUC patients in the Taiwan UTUC Collaboration Group, 685 UTUC cases with multifocal tumors (defined as more than one tumor lesion in unilateral upper urinary tract) were retrospectively included and divided into three groups: multiple renal pelvic tumors, multiple ureteral tumors, and synchronous renal pelvic and ureteral tumors included 164, 152, and 369 patients, respectively. We found the prevalence of carcinoma in situ was the highest in the synchronous group. In multivariate survival analyses, tumor distribution showed no difference in cancer-specific and disease-free survival, but there was a significant difference in bladder recurrence-free survival. The synchronous group had the highest bladder recurrence rate. In summary, tumor distribution did not influence the cancer-specific outcomes of multifocal UTUC, but synchronous lesions led to a higher rate of bladder recurrence than multiple renal pelvic tumors. We believe that the distribution of tumors reflects the degree of malignant involvement within the urinary tract, but has little significance for survival or disease progression.

6.
Biomedicines ; 9(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34572412

RESUMO

BACKGROUND: Despite its widespread use, the use of prostate-specific antigen (PSA) alone as a screening biomarker for prostate cancer (PCa) leads often to unwarranted prostate biopsy, over-diagnosis, and consequently, over-treatment, because of its limited specificity. There are reports that the apoptosis inhibitor of macrophage (AIM), secreted mainly by macrophages and epithelial cells, is upregulated during inflammation and facilitates immune recognition of cancerous cells by blocking human regulator of complement activation. OBJECTIVE: These controversies around the PSA utility necessitate a reexamination of its use as a screening tool. More so, despite the suggested implication of AIM in anticancer immunosurveillance, there is a dearth of information on its role in therapy response, disease progression, and clinical outcomes of patients with PCa. These inform the present study to probe the nature and role of AIM/PSA signaling in anticancer immunity and prognosis in PCa. METHODS: A combination of bioinformatics-aided statistical analyses, gene function annotation, and immune infiltrate analyses, coupled with tissue staining, and function assays, namely migration, invasion, and clonogenicity assays, we employed. RESULTS: We demonstrated that AIM and PSA expression levels are inversely correlated in PCa clinical samples and cell lines, with AIMlowPSAhigh defining PCa, compared to AIMhighPSAlow in normal samples. Concomitant aberrant PSA and significantly suppressed AIM expression levels positively correlated with high-grade disease and characterized by advanced stage prostate cancer, regardless of mutation status. We found that a high PSA/AIM ratio is associated with disease recurrence in patients with prostate cancer but is equivocal for overall survival. In addition, PSA-associated AIM suppression is implicated in the enhanced 'metastability' of PCa and a high AIM/PSA ratio is associated with strong castration-induced regression. CRISPR-mediated AIM knockout was associated with higher PSA expression while ectopic expression of AIM significantly attenuated the migration and invasive capability of PC3 and DU145 cells. Interestingly, compared to normal samples, we observed that AIM, biomarkers of T-cell activation and M1 phenotype markers are co-suppressed in PCa samples. CONCLUSION: Herein, we demonstrate that AIM/CD5L binds to PSA and that a high PSA/AIM ratio defines advanced stage PCa (regardless of mutation status), is implicated in enhanced metastability, and associated with disease recurrence, while a high AIM/PSA ratio is associated with strong castration-induced regression. More so, the ectopic expression of AIM significantly enhances the anticancer effect of Pembrolizumab and elicits an increased CD8+ T-cell count in AIMhiPSAloPDL1+ PCa cases that are respondent to Pembrolizumab treatment.

7.
Cancers (Basel) ; 13(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34439112

RESUMO

BACKGROUND: prostate cancer (PCa) is a principal cause of cancer-related morbidity and mortality. Castration resistance and metastasis are clinical challenges and continue to impede therapeutic success, despite diagnostic and therapeutic advances. There are reports of the oncogenic activity of genetic suppressor element (GSE)1 in breast and gastric cancers; however, its role in therapy resistance, metastasis, and susceptibility to disease recurrence in PCa patients remains unclear. OBJECTIVE: this study investigated the role of aberrantly expressed GSE1 in the metastasis, therapy resistance, relapse, and poor prognosis of advanced PCa. METHODS: we used a large cohort of multi-omics data and in vitro, ex vivo, and in vivo assays to investigate the potential effect of altered GSE1 expression on advanced/castration-resistant PCa (CRPC) treatment responses, disease progression, and prognosis. RESULTS: using a multi-cohort approach, we showed that GSE1 is upregulated in PCa, while tumor-associated calcium signal transducer 2 (TACSTD2) is downregulated. Moreover, the direct, but inverse, correlation interaction between GSE1 and TACSTD2 drives metastatic disease, castration resistance, and disease progression and modulates the clinical and immune statuses of patients with PCa. Patients with GSE1highTACSTD2low expression are more prone to recurrence and disease-specific death than their GSE1lowTACSTD2high counterparts. Interestingly, we found that the GSE1-TACSTD2 expression profile is associated with the therapy responses and clinical outcomes in patients with PCa, especially those with metastatic/recurrent disease. Furthermore, we demonstrate that the shRNA-mediated targeting of GSE1 (shGSE1) significantly inhibits cell proliferation and attenuates cell migration and tumorsphere formation in metastatic PC3 and DU145 cell lines, with an associated suppression of VIM, SNAI2, and BCL2 and the concomitant upregulation of TACSTD2 and BAX. Moreover, shGSE1 enhances sensitivity to the antiandrogens abiraterone and enzalutamide in vitro and in vivo. CONCLUSION: these data provide preclinical evidence of the oncogenic role of dysregulated GSE1-TACSTD2 signaling and show that the molecular or pharmacological targeting of GSE1 is a workable therapeutic strategy for inhibiting androgen-driven oncogenic signals, re-sensitizing CRPC to treatment, and repressing the metastatic/recurrent phenotypes of patients with PCa.

8.
Cancers (Basel) ; 13(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34439119

RESUMO

To assess the predictive value of tumor burden on the biochemical response, and radiological response in Taiwanese metastatic castration-resistant prostate cancer (mCRPC) patients receiving enzalutamide. The mCRPC patients treated with enzalutamide were recruited from three hospitals. High tumor burden (HTB) was classified as metastases at either appendicular bone or visceral organ. Good prostate-specific antigen (PSA) response was defined as PSA reduction of 80%. In this cohort, there were 104 (54.2%) HTB patients and 88 (45.8%) with low tumor burden (LTB). Compared to LTB patients, fewer HTB patients had good PSA response (odds ratio: 0.43, range: 0.22-0.87, p = 0.019) and fewer radiological response (complete and partial remission) (odds ratio: 0.78, range: 0.36-1.68, p = 0.52) to enzalutamide. The disease control rate which also contained stable disease, was still lower in HTB (76.0%) than LTB group (92.9%, OR: 0.24, range: 0.07-0.77, p = 0.016) in the multivariable model. In addition, HTB patients had significantly shorter progression-free survival duration than did LTB patients (median: 8.3 vs. 21.6 months, log-rank test p = 0.003) in the univariable analysis. The tumor burden before the use of enzalutamide was associated with treatment outcomes. HTB reduced PSA response rate, radiological response rate and progression-free survival duration.

9.
J Clin Med ; 10(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34441902

RESUMO

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), affecting over 90% of patients with symptomatic prostatitis, remains a therapeutic challenge and adversely affects patients' quality of life (QoL). This study probed for likely beneficial effects of ESWT, evaluating its extent and durability. PATIENTS AND METHODS: Standardized indices, namely the pain, urinary, and QoL domains and total score of NIH-CPSI, IIEF-5, EHS, IPSS, and AUA QoL_US were employed in this study of patients with CP/CPPS who had been refractory to other prior treatments (n = 215; age range: 32-82 years; median age: 57.5 ± 12.4 years; modal age: 41 years). RESULTS: For CP symptoms, the mean pre-ESWT NIH-CPSI total score of 27.1 ± 6.8 decreased by 31.3-53.6% over 12 months after ESWT. The mean pre-ESWT NIH-CPSI pain (12.5 ± 3.3), urinary (4.98 ± 2.7), and QoL (9.62 ± 2.1) domain scores improved by 2.3-fold, 2.2-fold, and 2.0-fold, respectively, by month 12 post-ESWT. Compared with the baseline IPSS of 13.9 ± 8.41, we recorded 27.1-50.9% amelioration of urinary symptoms during the 12 months post-ESWT. For erectile function, compared to pre-ESWT values, the IIEF-5 also improved by ~1.3-fold by month 12 after ESWT. This was corroborated by EHS of 3.11 ± 0.99, 3.37 ± 0.65, 3.42 ± 0.58, 3.75 ± 0.45, and 3.32 ± 0.85 at baseline, 1, 2, 6, and 12 months post-ESWT. Compared to the mean pre-ESWT QoL score (4.29 ± 1.54), the mean QoL values were 3.26 ± 1.93, 3.45 ± 2.34, 3.25 ± 1.69, and 2.6 ± 1.56 for months 1, 2, 6, and 12 after ESWT, respectively. CONCLUSIONS: This study shows ESWT, an outpatient and easy-to-perform, minimally invasive procedure, effectively alleviates pain, improves erectile function, and ameliorates quality of life in patients with refractory CP/CPPS.

10.
Cancers (Basel) ; 13(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34298692

RESUMO

Background: Testosterone plays a critical role in prostate development and pathology. However, the impact of the molecular interplay between testosterone-associated genes on therapy response and susceptibility to disease relapse in PCa patients remains underexplored. Objective: This study investigated the role of dysregulated or aberrantly expressed testosterone-associated genes in the enhanced dissemination, phenoconversion, and therapy response of treatment-resistant advanced or recurrent PCa. Methods: Employing a combination of multi-omics big data analyses, in vitro, ex vivo, and in vivo assays, we assessed the probable roles of HSD17B2, HSD17B3, SHBG, and SRD5A1-mediated testosterone metabolism in the progression, therapy response, and prognosis of advanced or castration-resistant PCa (CRPC). Results: Our bioinformatics-aided gene expression profiling and immunohistochemical staining showed that the aberrant expression of the HSD17B2, HSD17B3, SHBG, and SRD5A1 testosterone metabolic tetrad characterize androgen-driven PCa and is associated with disease progression. Reanalysis of the TCGA PRAD cohort (n = 497) showed that patients with SRD5A1-dominant high expression of the tetrad exhibited worse mid-term to long-term (≥5 years) overall survival, with a profoundly shorter time to recurrence, compared to those with low expression. More so, we observed a strong association between enhanced HSD17B2/SRD5A1 signaling and metastasis to distant lymph nodes (M1a) and bones (M1b), while upregulated HSD17B3/SHBG signaling correlated more with negative metastasis (M0) status. Interestingly, increased SHBG/SRD5A1 ratio was associated with metastasis to distant organs (M1c), while elevated SRD5A1/SHBG ratio was associated with positive biochemical recurrence (BCR) status, and shorter time to BCR. Molecular enrichment and protein-protein connectivity network analyses showed that the androgenic tetrad regulates testosterone metabolism and cross-talks with modulators of drug response, effectors of cell cycle progression, proliferation or cell motility, and activators/mediators of cancer stemness. Moreover, of clinical relevance, SHBG ectopic expression (SHBG_OE) or SRD5A1 knockout (sgSRD5A1) induced the acquisition of spindle fibroblastoid morphology by the round/polygonal metastatic PC-3 and LNCaP cells, attenuated their migration and invasion capability, and significantly suppressed their ability to form primary or secondary tumorspheres, with concomitant downregulation of stemness KLF4, OCT3/4, and drug resistance ABCC1, ABCB1 proteins expression levels. We also showed that metronomic dutasteride synergistically enhanced the anticancer effect of low-dose docetaxel, in vitro, and in vivo. Conclusion: These data provide proof of concept that re-reprogramming of testosterone metabolism through "SRD5A1 withdrawal" or "SHBG induction" is a workable therapeutic strategy for shutting down androgen-driven oncogenic signals, reversing treatment resistance, and repressing the metastatic/recurrent phenotypes of patients with PCa.

11.
Sci Rep ; 11(1): 4040, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597574

RESUMO

Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan-Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.

12.
BMC Cancer ; 21(1): 80, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468084

RESUMO

BACKGROUND: A high incidence of upper urinary tract urothelial carcinoma has been reported in the southwestern area of Taiwan, where arsenic water contamination was considered the main cause. However, there is no definite proof to show a correlation between arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival, and cancer-specific survival. METHODS: The records of a total of 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from the medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups. RESULTS: Female predominance was revealed in both endemic and non-endemic groups (male:female ratio = 1:1.2-1.4). No statistical differences were found in histological types, staging, and tumor size between the two groups. Nonetheless, patients with characteristics of aging and having end-stage renal disease were outnumbered in the non-endemic group, while a higher prevalence of previous bladder tumors and more ureteral tumors were found in the endemic group. Adjusted stratified cumulative survival curves suggested a poorer prognosis in endemic patients, especially in disease-free survival of early stage disease. CONCLUSIONS: A higher mortality rate with more previous bladder cancer history and ureteral tumors was seen in patients with upper urinary tract urothelial carcinoma residing in the arsenic water contamination area. This may be attributed to the long-term carcinogenic effect of arsenic underground water.


Assuntos
Arsenicais/efeitos adversos , Carcinoma de Células de Transição/epidemiologia , Neoplasias Renais/epidemiologia , Doenças Vasculares Periféricas/epidemiologia , Neoplasias Ureterais/epidemiologia , Idoso , Carcinoma de Células de Transição/induzido quimicamente , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Intervalo Livre de Doença , Doenças Endêmicas/estatística & dados numéricos , Feminino , Geografia , Humanos , Incidência , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/induzido quimicamente , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Neoplasias Ureterais/induzido quimicamente , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/patologia , Poluição Química da Água/estatística & dados numéricos
13.
J Microbiol Immunol Infect ; 54(2): 193-205, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31296484

RESUMO

BACKGROUND: Patients with diabetes mellitus (DM) have higher incidence and more severe urinary tract infections (UTIs) for longer duration than those of the patients without DM. It causes more complicated etiologies during uropathogenic Escherichia coli (UPEC) infection. However, studies regarding the molecular mechanism are scarce. METHODS: The present study (1) aimed to verify if sugar influences the process of UPEC-induced cystitis and invasion into the uroepithelial cells and (2) illustrated the mechanism of effects for sugar enhanced the UPEC infection into uroepithelial cells is related to TLR-4-mediated and JAK/STAT1-dependent pathway. RESULTS: The results of the present study indicated that sugar can enhance UPEC infection in uroepithelial cells by up-regulating the transduced circuit between TLR-4-mediated UPEC interaction and JAK/STAT-1 signal pathways. The results of the inhibitor-co-incubating experiments demonstrated that the mechanism involved in the synergistic amplification of TLR-4-mediated UPEC interaction and JAK/STAT1 signaling pathways is responsible for the increased UPEC infection in uroepithelial cells. CONCLUSION: The results also proved that STAT-1 plays a critical role in the regulation of UPEC invasion and infection in the uroepithelial cells, especially those pretreated with glucose. The present study suggests a possible therapeutic approach to preferentially suppress UPEC infection during UTIs in the patients with diabetes.

14.
J Clin Med ; 9(12)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33261187

RESUMO

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121-1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169-2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095-1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141-1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

15.
Am J Mens Health ; 14(6): 1557988320977630, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33319613

RESUMO

The p16/Ki67 dual immunostaining was performed on anal cytology specimens; this is an anal cancer screening method. A literature search was performed in the BioMed Central, Cochrane Library, Embase, Google Scholar, and PubMed electronic databases for relevant articles. We included studies that discussed the efficacy of p16/Ki67 dual immunostaining for detecting anal intraepithelial neoplasia (AIN). Studies that calculated the diagnostic efficacy on a per-patient basis were included. We excluded review articles, case series, and studies that did not provide sufficient information. We extracted data on true positive, true negative, false positive, and false negative from the included studies to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). All analyses were performed with a random-effects model using MetaDiSc 1.4 and MetaDTA. The meta-analysis produced a pooled sensitivity of 0.63 (95% CI: 0.34, 0.86) and specificity of 0.65 (95% CI: 0.46, 0.81) for p16/Ki67 dual immunostaining in detecting AIN. The pooled DOR was 3.26 (95% CI: -0.29, 6.82). A subgroup analysis of HIV-infected men who have sex with men (MSM) demonstrated a pooled sensitivity of 0.75 (95% CI: 0.28, 0.96). p16/Ki67 dual immunostaining might have a higher sensitivity for detecting AIN in HIV-infected MSM. p16/Ki67 dual immunostaining might be more sensitive in HIV-infected MSM and has higher specificity compared to human papillomavirus testing among this high-risk group. p16/Ki67 dual immunostaining might be an adjuvant and potential triage test for anal cytology in anal cancer screening.


Assuntos
Neoplasias do Ânus , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Neoplasias do Ânus/diagnóstico , Homossexualidade Masculina , Humanos , Antígeno Ki-67 , Masculino , Infecções por Papillomavirus/diagnóstico
16.
Int J Med Microbiol ; 310(7): 151450, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33092696

RESUMO

BACKGROUND: UPEC can internalize clonally in prostate to form biofilm-like intracellular bacterial communities (IBCs) for recurrent or chronic infection. We previously indicated that the exposure of prostate cells to testosterone could suppress UPEC invasion and their persistent survival within cells by effectively inhibiting the JAK/STAT1 signaling pathway. However, the regulatory mechanism by which testosterone affects UPEC-induced prostatitis via STAT3, another latent transcription factor signaling pathway is still unclear. The present study aimed to clarify the role of STAT3 in the process of UPEC-induced inflammation and colonization in prostate epithelial cells. METHODS: The effects of testosterone-mediated inhibition were compared between the prostatitis by different UPEC strains (CFT073 and J96) through the specific GFP-UPEC-infected prostate cell model. Fluorescence microscopy was used for UPEC IBCs detection and quantifying, and Flow cytometry, RT-PCR and western blotting were used for analyzing related gene and protein expressions. Pretreatment of JAK and STAT3 inhibitors were also applied to verify the regulation of transduction pathway in testosterone-mediated anti-UPEC infection. RESULTS: This study revealed that testosterone effectively suppresses UPEC infection and IBC formation in prostate cells through the JAK/STAT3 pathway. The results show that CFT073 and J96 UPEC infection rates and colony numbers were dose-dependently reduced in RWPE-1 cells pretreated with 5 and 20 µg/mL testosterone at 0 and 24 h post-infection. Further, testosterone reduced the amounts of UPEC infecting and surviving within the prostate cells, as well as suppressed the size of IBCs formed. We demonstrated that pretreating testosterone effectively inhibited UPEC infection along with dose-dependent suppression of STAT3 and the phosphorylated-STAT3 expression in prostate cells, especially in 24 h J96 UPEC infected groups. The STAT inhibitor, SOCS3 also up-regulated at the same time. In addition, we pretreated the JAK1 or STAT3 inhibitor with testosterone to block the signaling transduction before CFT073 and J96 UPEC infection, and found the significant restoring in both the sizes of IBCs and bacterial numbers in RWPE-1 cells. Therefore, our results suggest that the suppression of STAT3 by testosterone treatment attenuate UPEC growing within IBCs and interfere with their infection to prostate cells. CONCLUSIONS: Overall, our study demonstrates that testosterone suppresses the initial infection of prostate epithelial cells by UPEC and reduces the survival of UPEC within IBCs after infection. These results indicate a critical role for STAT3 in facilitating UPEC infection and persistence, and its participation in driving testosterone-suppressive responses in prostate epithelial cells. In conclusion, this study suggests that testosterone may be beneficial in treating clinically recurrent UPEC infections and, thus, the persistent recurrence of prostatic inflammation.


Assuntos
Infecções por Escherichia coli , Escherichia coli Uropatogênica , Biofilmes , Células Epiteliais , Humanos , Masculino , Próstata , Fator de Transcrição STAT3 , Testosterona
17.
Cytokine ; 131: 155112, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32361400

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) is the key regulator of angiogenesis in the development of various cancers. Previous studies have examined the relationship between VEGF gene promoter polymorphisms such as -2578C/A and -460C/T and bladder cancer risk; however, these results are inconclusive. Therefore, we performed this meta-analysis to investigate the association between VEGF gene promoter polymorphisms and bladder cancer risk. METHODS: PubMed, Embase, Cochrane Library and Web of Science databases were searched for studies published before September 2018. The methodological quality assessment of included studies was performed based on the Newcastle-Ottawa Quality Scale (NOS). We conducted a systematic review and meta-analysis using both fixed- and random-effect model. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the relationship. In addition, the stability of our analysis was evaluated by heterogeneity, sensitivity, subgroup of ethnicity, and publication bias analysis. RESULTS: We finally included 7 case-control studies with a total of 2412 bladder cancer patients and 3157 cancer-free controls. In Asian population with the VEGF -2578C/A polymorphism, significantly higher bladder cancer risks of 1.55 (95% CI = 1.25-1.93) and 1.53 (95% CI = 1.11-2.10) were found in the heterozygous model (AC vs CC) and the dominant model (AA + AC vs CC), respectively. Though there was no statistical association between VEGF -460C/T polymorphism and bladder cancer, a tendency to higher bladder cancer risk was observed in various genetic models (T vs C; TT vs CC; TC vs CC and TT + TC vs CC). CONCLUSIONS: Our findings suggest that VEGF -2578C/A polymorphism might be a risk factor with a modest significance for bladder cancer only in Asian population. Further studies with a larger sample size and other functional polymorphisms are needed to explore the effects of VEGF gene on the risk of bladder cancer.


Assuntos
Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/genética , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Humanos , Regiões Promotoras Genéticas
18.
Rapid Commun Mass Spectrom ; 34(15): e8825, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32396680

RESUMO

RATIONALE: Oriental Beauty, a type of oolong tea native to Taiwan, is highly prized by connoisseurs for its unique fruity aroma and sweet taste. Leaves of Oriental Beauty vary in appearance, aroma, and taste, depending on the degree of tea green leafhopper (Jacobiasca formosana) infestation. In this study, the aim is to investigate the differential expression of proteins in leaves with low, medium, and high degrees of leafhopper infestation. METHODS: Proteomic techniques 2DE (two-dimensional electrophoresis) and nanoscale liquid chromatography/tandem mass spectrometry (LC/MS/MS) were used to investigate the differential expression of proteins in tea leaves with different degrees of leafhopper infestation. RESULTS: A total of 89 proteins were found to exhibit significant differences in expression. In a gene ontology analysis, most of these proteins participated in biosynthesis, carbohydrate metabolism, transport, responses to stress, and amino acid metabolism. CONCLUSIONS: These results indicated that the unique aroma and taste of the leaves might be influenced by their protein expression profiles, as well as related factors such as defensive responses to tea green leafhopper saliva.


Assuntos
Camellia sinensis/parasitologia , Hemípteros/fisiologia , Folhas de Planta/química , Animais , Camellia sinensis/química , Camellia sinensis/genética , Camellia sinensis/metabolismo , Cromatografia Líquida , Comportamento Alimentar , Aromatizantes/química , Aromatizantes/metabolismo , Odorantes/análise , Folhas de Planta/genética , Folhas de Planta/metabolismo , Folhas de Planta/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica , Taiwan , Espectrometria de Massas em Tandem
19.
Sci Rep ; 10(1): 8261, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427884

RESUMO

Signaling elicited by the stem cell factors SOX2, OCT4, KLF4, and MYC not only mediates reprogramming of differentiated cells to pluripotency but has also been correlated with tumor malignancy. In this study, we found SOX2 expression signifies poor recurrence-free survival and correlates with advanced pathological grade in bladder cancer. SOX2 silencing attenuated bladder cancer cell growth, while its expression promoted cancer cell survival and proliferation. Under low-serum stress, SOX2 expression promoted AKT phosphorylation and bladder cancer cells' spheroid-forming capability. Furthermore, pharmacological inhibition of AKT phosphorylation, using MK2206, inhibited the SOX2-mediated spheroid formation of bladder cancer cells. Gene expression profiling showed that SOX2 expression, in turn, induced IGF2 expression, while SOX2 silencing inhibited IGF2 expression. Moreover, knocking down IGF2 and IGF1R diminished bladder cancer cell growth. Lastly, pharmacological inhibition of IGF1R, using linsitinib, also inhibited the SOX2-mediated spheroid formation of bladder cancer cells under low-serum stress. Our findings indicate the SOX2-IGF2 signaling affects the aggressiveness of bladder cancer cell growth. This signaling could be a promising biomarker and therapeutic target for bladder cancer intervention.


Assuntos
Fator de Crescimento Insulin-Like II/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Humanos , Fator de Crescimento Insulin-Like II/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Fatores de Transcrição SOXB1/genética , Transdução de Sinais , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
20.
Medicine (Baltimore) ; 99(7): e18842, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049786

RESUMO

Acute urinary retention (AUR) is associated with hormone imbalance in men. However, limited studies focused on exploring the complications of AUR in patients with prostate cancer (PC) who receive androgen deprivation therapy (ADT). Therefore, we aim to evaluate the subsequent risk of AUR in ADT-treated PC patients. We collected data from 24,464 male patients who were newly diagnosed with prostate malignancy from a longitudinal health insurance database of catastrophic illness in 2000 to 2008. All PC patients were categorized into 2 cohorts, namely, ADT cohort and non-ADT cohort, based on whether or not the patient receives ADT. The patients were followed up until the occurrence of AUR. Multivariate Cox proportional hazard regression and Kaplan-Meier analysis were performed. After a 12-year follow-up, the incidence rates of AUR were 12.49 and 9.86 per 1000 person-years in ADT and non-ADT cohorts, respectively. Compared with the non-ADT cohort, the ADT cohort had a 1.21-fold increase in AUR risk based on the adjusted model (95% CI = 1.03-1.43). In addition, PC patients receiving early ADT treatment within 6 months or receiving only luteinizing hormone-releasing hormone treatment also had significantly increased risk of AUR. ADT was positively associated with AUR risk. PC patients receiving ADT should be informed about the risks of bladder outlet obstruction and AUR, and they may benefit from screening for related risk factors. New guidelines and treatments should be proposed in the future to manage ADT-related lower urinary tract symptoms and reduce the risk of AUR.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Retenção Urinária/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Estudos de Casos e Controles , Humanos , Incidência , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taiwan/epidemiologia , Retenção Urinária/induzido quimicamente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...