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OBJECTIVE: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. METHODS: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. RESULTS: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. CONCLUSION: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.
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MicroARNs , Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Retroalimentación , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patologíaRESUMEN
ABSTRACT Objective: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. Methods: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. Results: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. Conclusion: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.
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Background: lncRNAs affect adaptive and innate immunity of cancer via mediating functional states of immune cells, genes, and pathways. Nonetheless, little is known about the molecular mechanism of lncRNA-mediated CD8+ T cell immune infiltration in progression of clear cell renal cell carcinoma (ccRCC). We designed this work to investigate the role of LINC00887 in regulating CD8+ T cell immune infiltration in ccRCC. Methods: Correlation between LINC00887 and immune factors and the expression level of LINC00887 in ccRCC were analyzed by bioinformatics methods (TCGA-KIRC database, "edgeR" package, "clusterProfiler" package, and "CIBERSORT" package). LINC00887 expression in ccRCC was examined via RT-qPCR. The cytokilling capacity of CD8+ T cells was evaluated by the lactate dehydrogenase assay. The apoptotic ability of CD8+ T cells was measured by flow cytometry. The chemotactic ability of CD8+ T cells was revealed by chemotaxis assay. CXCR3, CXCL9, and CXCL10 levels were assessed by RT-qPCR. Results: As suggested by bioinformatics analysis, LINC00887 was markedly upregulated in ccRCC patients and associated with expression of immune-suppression molecule, thereby abating the immune infiltration level of CD8+ cells in tumor tissue. As revealed by cellular assay, LINC00887 was upregulated in ccRCC cells, and knockdown of LINC00887 resulted in a decreased PD-L1 expression, increased CD8+ T cell toxicity, decreased apoptotic levels, and enhanced chemotaxis. Moreover, we found that LINC00887 exhibited inhibitory effect on immune infiltration of CD8+ cells in clinical tissues. Conclusions: The results of this study suggested that LINC00887 promoted ccRCC progression by inhibiting immune infiltration of CD8+ T cells, providing new insights into pathogenesis of ccRCC and suggesting LINC00887 being a promising immunotherapy target for ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , ARN Largo no Codificante , Linfocitos T CD8-positivos , Carcinoma de Células Renales/genética , Humanos , Inmunoterapia , Neoplasias Renales/genética , ARN Largo no Codificante/genéticaRESUMEN
We focused on studying the effects of a key miRNA-mRNA axis in bladder urothelial carcinoma (BUC). Firstly, miRNAs and mRNAs differentially expressed in BUC were analyzed. Clinical information in the TCGA database was used for survival analysis, and the regulator of miRNA-93-5p was predicted. miRNA-93-5p and KLF9 mRNA expression were detected by qRT-PCR. Protein level detection and targeting measurement were, respectively, achieved by western blot and dual-luciferase approaches. The proliferative, invasive, and migratory abilities were tested through CCK-8, Transwell, and wound healing methods. Cell apoptosis in each group was detected through flow cytometry. As discovered, miRNA-93-5p level was markedly high in BUC cells while KLF9 expression was remarkably low. miRNA-93-5p overexpression promoted BUC cell abilities. Besides, miRNA-93-5p inhibited KLF9 expression. Furthermore, KLF9 overexpression dramatically attenuated such promotion on cancer cell abilities. On the whole, miRNA-93-5p/KLF9 axis facilitated BUC progression, offering a new potential target for BUC patients.
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Carcinoma de Células Transicionales , MicroARNs , Neoplasias de la Vejiga Urinaria , Proliferación Celular/genética , Femenino , Humanos , Factores de Transcripción de Tipo Kruppel/genética , Masculino , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
OBJECTIVE: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. METHODS: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. RESULTS: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively (p = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively (p = 0.002). CONCLUSION: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.
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The aim of this study was to examine correlation between low cytoplasmic expression of VPS33B and clinicopathologic features of renal cell carcinoma (RCC). In this study, ninety RCC patients ranging from years 2006 to 2012 were reviewed. VPS33B expression in tumor tissues and adjacent normal tissues was examined using immunohistochemistry (IHC) and association of VPS33B expression with RCC patient clinicopathologic parameters was evaluated. Final staining scores of 0-5 and 6-7 were respectively considered to be low and high expression. Immunohistochemical analysis confirmed that VPS33B protein expression was predominantly localized in cytoplasm of both RCC and adjacent normal tissues. Lower cytoplasmic VPS33B expression was observed in RCC compared to normal cells (P = 0.007). In addition, cytoplasmic VPS33B protein levels in tumor tissues were correlated with T stage (T1 vs. T2 vs. T3) (P = 0.038), stage (I-II vs. III-IV) (P = 0.035), and renal vein invasion (P = 0.039) of RCC patients. Lower RCC cytoplasmic VPS33B expression had a significantly shorter disease free survival (DFS) compared to the higher expression group (P = 0.030). Multivariate analysis suggested that low cytoplasmic VPS33B expression was an independent predictor for DFS of RCC patients. (P = 0.030). Our results suggest that low cytoplasmic VPS33B expression is a potential unfavorable prognostic factor for progression and prognosis of RCC.
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OBJECTIVES: To develop and validate an individualized nomogram to predict probability of patients with ureteral calculi developing into urosepsis. METHODS: The clinical data of 747 patients with ureteral calculi who were admitted from June 2013 to December 2015 in Affiliated Nanhai Hospital of Southern Medical University were selected and included in the development group, while 317 ureteral calculi patients who were admitted from January 2016 to December 2016 were included in the validation group. The independent risk factors of ureteral calculi associated with urosepsis were screened using univariate and multivariate logistic regression analyses. The corresponding nomogram prediction model was drawn according to the regression coefficients. The area under the receiver operating characteristic curves and the GiViTI calibration belts were used to estimate the discrimination and calibration of the prediction model, respectively. RESULTS: Multivariate logistic regression analysis showed that the five risk factors of gender, mean computed tomography(CT) attenuation value of hydronephrosis, functional solitary kidney, urine white blood cell(WBC) count and urine nitrite were independent risk factors of ureteral calculi associated with urosepsis. The areas under the receiver operating characteristic curve of the development group and validation group were 0.913 and 0.874 respectively, suggesting that the new prediction model had good discrimination capacity. P-values of the GiViTI calibration test of the two groups were 0.247 and 0.176 respectively, and the 95% CIs of GiViTI calibration belt in both groups did not cross the diagonal bisector line. Therefore the predicted probability of the model was consistent with the actual probability which suggested that the calibration of the prediction model in both groups were perfect and prediction model had strong concordance performance. CONCLUSION: The individualized prediction model for patients with ureteral calculi can facilitate improved screening and early identification of patients having higher risk of urosepsis.
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Modelos Biológicos , Nomogramas , Sepsis/epidemiología , Sepsis/etiología , Cálculos Ureterales/complicaciones , Cálculos Ureterales/epidemiología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Sepsis/diagnóstico por imagen , Sepsis/terapia , Factores Sexuales , Tomografía Computarizada por Rayos X , Cálculos Ureterales/diagnóstico por imagen , Cálculos Ureterales/terapiaRESUMEN
PURPOSE: The purpose of this study was to investigate the expression of long-chain non-coding RNA (lncRNA) SNHG7 in bladder cancer tissues and cell lines, and to explore its impact on bladder cancer cell proliferation, apoptosis and invasion processes. METHODS: Bladder cancer tissues and near-cancer tissues were collected. The expression of lncRNA-SNHG7 in tissues and cell lines was detected by real-time PCR (RT-PCR). The expression of lncRNA-SNHG7 was downregulated by RNA interference (siRNA) as detected by RT-PCR that was used to detect the interference efficiency. CCK-8, flow cytometry and Transwell assays were used to evaluate the effect of lncRNASNHG7 on the proliferation, apoptosis and invasion capability of bladder cancer cells. The downregulation effect of lncRNA-SNHG7 on Epithelial-Mesenchymal Transition (EMT) related markers was tested by westernblot. RESULTS: lncRNA-SNHG7 was upregulated in bladder cancer cell lines. After the expression of lncRNA-SNHG7 was downregulated, the proliferation of bladder cancer cells was decreased, the apoptosis was increased, and the invasion ability of cells was decreased. The expression of E-cadherin was increased, but the expression of N-cadherin, vimentin and snail were decreased. Increased expression of lncRNASNHG7 in cancer tissues was significantly related to tumor size, metastasis and stage. CONCLUSIONS: This study showed that lncRNA -SNHG7 is overexpressed in bladder cancer tissues and cells. Downregulation of lncRNA-SNHG7 can inhibit the proliferation of bladder cancer cells and promote apoptosis, as well as inhibit cell invasion, which provides a potential molecular target for future tumor targeted therapy.
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Apoptosis/genética , Proliferación Celular/genética , Invasividad Neoplásica/genética , ARN Largo no Codificante/genética , Neoplasias de la Vejiga Urinaria/genética , Cadherinas/genética , Línea Celular Tumoral , Movimiento Celular/genética , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Interferencia de ARN/fisiología , ARN Interferente Pequeño/genética , Regulación hacia Arriba/genética , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in human renal cell carcinoma (RCC) tissues and established/primary human RCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells. THOR silencing (by targeted siRNAs) or CRISPR/Cas9 knockout inhibited RCC cell growth, viability and proliferation in vitro. Reversely, forced over-expression of THOR promoted RCC cell survival and proliferation. IGF2BP1-regulated genes, including IGF2, GLI1 and Myc, were downregulated by THOR silencing or knockout, but they were upregulated after THOR over-expression. In vivo, THOR-knockout 786-O tumors grew significantly slower than the control tumors in nude mice. CONCLUSION: THOR expression promotes RCC cell growth in vitro and in vivo. THOR could be a novel and important therapeutic target for human RCC.
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Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Animales , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular , Humanos , Riñón/metabolismo , Riñón/patología , Neoplasias Renales/patología , Masculino , Ratones Desnudos , Persona de Mediana Edad , Proteínas de Unión al ARN/genética , Células Tumorales CultivadasRESUMEN
BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.
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Adrenocortical carcinoma (ACC) is a rare, but aggressive endocrine malignancy with a generally poor clinical outcome. There is no effective therapy for advanced and metastatic ACC. In our study, we found that an existing drug (rottlerin) exerted its tumour-suppressive function in ACC. Specifically, rottlerin inhibited cellular proliferation of ACC cell lines (NCI-H295R and SW-13) in a dose- and time-dependent manner. We also found that rottlerin induced cell apoptosis and promoted G0/G1 cell cycle arrest in ACC cell lines. The cellular migration and invasion of ACC cell lines were decreased after treatment with rottlerin. Further, the molecular expression of lipoprotein receptor related protein 6 (LRP6) and ß-catenin were down-regulated in rottlerin-treated ACC cells, which indicated that Wnt/ß-catenin signaling was involved in the tumour-suppressive function of rottlerin. To further confirm the anti-tumour function of rottlerin, a nude mouse ACC xenograft model was used. The xenograft growth curves and TUNEL assays demonstrated that rottlerin inhibited proliferation and induced apoptosis in the ACC xenograft model. Furthmore, we verified that rottlerin down-regulated the expression of LRP6 and ß-catenin in vivo. The ACC cell line and xenograft mouse model data indicated that rottlerin significantly inhibited proliferation and induced apoptosis of ACC cells, likely via suppression of the Wnt/ß-catenin signaling pathway. Our study indicated the potential therapeutic utility of rottlerin as a novel and potential chemotherapeutic agent for ACC.
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Acetofenonas/farmacología , Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Benzopiranos/farmacología , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Vía de Señalización Wnt/efectos de los fármacos , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/patología , Animales , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of the present study was to explore sunitinib-induced autophagic effects and the specific molecular mechanisms involved, in vitro, using PC-3 and LNCaP human prostate cancer cell lines. Cells were exposed to escalating doses of sunitinib treatment and subsequent cell viability and cell cycle analyses were performed to evaluate the inhibitory effect of sunitinib in vitro. Immunofluorescence staining of microtubule associated protein 1A/1B-light chain 3 (LC3) puncta was employed to assess autophagy levels after sunitinib treatment. Western blot analysis was performed to evaluate variations in the levels of LC3, sequestosome-1, extracellular signal regulated kinase 1/2 (ERK1/2), mammalian target of rapamycin (mTOR), p70 ribosomal protein S6 kinase (p70S6K) and cleaved caspase-3 proteins. The present study revealed that sunitinib treatment inhibited cell growth and triggered autophagy in a dose-dependent manner in both cell lines. In addition, sunitinib activated ERK1/2 and inhibited mTOR/p70S6K signaling. Sunitinib-induced autophagy was notably reversed by ERK1/2 kinase inhibitor, U0126. Furthermore, inhibition of sunitinib-induced autophagy by 3-methyladenine enhanced apoptosis and exhibited improved cell viability, which indicated that sunitinib induces not only apoptosis but also autophagic cell death in prostate cancer cell lines. These results may lead to an improved understanding of the mechanism of sunitinib's cytotoxic action and may provide evidence that combined sunitinib autophagy-regulating treatment may be of benefit to anti-prostate cancer therapy.
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OBJECTIVE: To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant. METHODS: Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. RESULTS: High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups. CONCLUSIONS: The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.
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Supervivencia de Injerto , Modelos Animales , Trasplante de Pene , Reimplantación , Adulto , Anastomosis Quirúrgica , Animales , Arterias/cirugía , Perros , Estudios de Factibilidad , Humanos , Masculino , Microcirugia , Necrosis/etiología , Tempo Operativo , Pene/anatomía & histología , Pene/patología , Complicaciones Posoperatorias/etiología , Tasa de Supervivencia , Micción , Venas/cirugíaRESUMEN
Bladder cancer is still a common malignancy of the urinary tract due to the high metastasis rate and unexpected side effects of drug treatments. The acidic environment of the urinary bladder also strongly limits the efficacy of the chemotherapeutic agents during the treatment of bladder cancer. In this study, a series of selenadiazole derivatives (SeDs) have been rationally designed and synthesized and could actively suppress the progression and metastasis of bladder cancer cells. SeDs demonstrated better antiproliferative activity and higher stability under different physiological conditions, especially in an acidic urocystic environment, than mitomycin, a clinically used anti-bladder cancer drug. In particular, compound 1b displayed better selectivity between cancer and normal cells in comparison with other compounds. Studies on the structure-activity relationship revealed that the introduction of strong electron donating substituents, such as the methoxy group, resulted in a dramatic enhancement in the anticancer efficacy. Furthermore, 1b induced anti-migration and anti-invasion activities against bladder cancer cells. Mechanistic investigation revealed that compound 1b was able to enter the cells through endocytosis and then trigger reactive oxygen species (ROS) overproduction, further causing DNA damage-mediated p53 phosphorylation and promoting cancer cell apoptosis by regulating the AKT and MAPKs signaling pathways. Altogether, the study provides a strategy for rational design of selenadiazole derivatives with improved stability to antagonize bladder cancer.
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Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Compuestos de Organoselenio/química , Compuestos de Organoselenio/farmacología , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Línea Celular , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Humanos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Invasividad Neoplásica/prevención & control , Transducción de Señal/efectos de los fármacos , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/metabolismo , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Metastatic renal cell carcinoma (RCC) disseminates to a number of organ sites and few patients demonstrate long-term survival following surgery. However, synchronous metastasis of RCC to the contralateral adrenal gland and pancreas is rare. In the present report, a case of synchronous RCC metastasis to the contralateral adrenal gland and pancreas in a 55-year-old patient, with an 116×92×61 mm right renal tumor and a 96×79×57 mm left adrenal lesion, is described. In April 2007, right nephrectomy was performed to treat the RCC, left adrenalectomy was performed to treat the adrenal tumor and the pancreatic metastases were resected. The patient remained alive at the 7-year follow-up appointment.
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n-3 polyunsaturated fatty acids (PUFAs) are essential for human health and have been reported to reduce the risk of cancer, inhibit the growth of various types of tumors both in vitro and in vivo, and affect adrenal function. However, their effects on adrenocortical carcinoma (ACC) are not known. In the present study, we demonstrated that docosahexenoic acid (DHA) inhibited ACC cell proliferation, colony formation and cell cycle progression, and promoted apoptosis. In addition, ectopic expression of fat-1, a desaturase that converts n-6 to n-3 PUFAs endogenously, also inhibited ACC cell proliferation. Moreover, supplementing n-3 PUFAs in the diet efficiently prevented ACC cell growth in xenograft models. Notably, implanted ACC cells were unable to grow in fat-1 transgenic severe combined immune deficiency mice. Further study revealed that exogenous and endogenous n-3 PUFAs efficiently suppressed both mTOR complex 1 (mTORC1) and mTORC2 signaling in ACC in vitro and in vivo. Taken together, our findings provide comprehensive preclinical evidence that n-3 PUFAs efficiently prevent ACC growth by inhibiting mTORC1/2, which may have important implications in the treatment of ACC.
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Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Ácidos Docosahexaenoicos/farmacología , Complejos Multiproteicos/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/patología , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Femenino , Humanos , Diana Mecanicista del Complejo 1 de la Rapamicina , Diana Mecanicista del Complejo 2 de la Rapamicina , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Ratones SCID , Complejos Multiproteicos/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This is an original research of penis allotransplantation. The paper presents an experiment allogenic penis transplantation model in Beagles, with a focus on recovery of blood supply and changes in tissue architecture. Twenty adult Beagles were allocated to 10 pairs for penile transplantation. After operation, the skin and glans were observed. If adverse symptoms occurred, the transplanted penis was resected and pathologically examined. Frequency of urination, urinary stream, and patency level were recorded 7 days after transplantation. Cystourethrography was performed on Day 10. The transplanted penises were resected on Day 14 for pathological examination. The research showed that transplanted penises survived after allotransplantation, and the dogs regained urination ability. Penis autotransplantation in Beagles is feasible. This preliminary study shows a potential for application of this new procedure for penis transplantation in humans.
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Trasplante de Pene , Procedimientos de Cirugía Plástica , Trasplante Homólogo/métodos , Animales , Perros , Masculino , Pene/irrigación sanguínea , Pene/cirugíaRESUMEN
OBJECTIVE: To evaluate the effect of ejaculatory duct dilation combined with seminal vesicle clysis in the treatment of refractory hematospermia. METHODS: Using ureteroscopy, we treated 32 patients with refractory hematospermia by transurethral dilation of the ejaculatory duct combined with clysis of the seminal vesicle with diluent gentamicin. RESULTS: The operation was successfully accomplished in 31 cases, with the mean operation time of 32 (26ï¼47) minutes. The patients were followed up for 6ï¼39 (mean 23.6) months. No complications, such as urinary incontinence and retrograde ejaculation, were found after operation. Hematospermia completely disappeared in 27 cases, was relieved in 1, and recurred in 3 after 3 months postoperatively. Those with erectile dysfunction or mental anxiety symptoms showed significantly decreased scores of IIEF-Erectile Function (IIEF-EF) and Self-Rating Anxiety Scale (SAS). CONCLUSIONS: Ejaculatory duct dilation combined with seminal vesicle clysis under the ureteroscope, with its the advantages of high effectiveness and safety, minimal invasiveness, few complications, and easy operation, deserves general clinical application in the treatment of refractory hematospermia.
Asunto(s)
Conductos Eyaculadores/cirugía , Hematospermia/cirugía , Vesículas Seminales/cirugía , Dilatación , Enfermedades de los Genitales Masculinos , Humanos , Masculino , Periodo Posoperatorio , Recurrencia , UreteroscopíaRESUMEN
The present study aimed to determine whether actinomycin X2 (AX2) intercepted the mTOR/PTEN/PI3K/Akt signaling pathway to inhibit human prostate cancer cells (PC-3) in vitro. The effects of AX2 on mTOR, PTEN, PI3K, and Akt at the protein level and mRNA were determined by western blotting and real-time reverse transcription-PCR (RT-PCR), respectively. Concurrently, the effects of AX2 on expression levels of MiRNA144 and MiRNA126 in PC-3 were measured by real-time RT-PCR. The association of MiRNA144 with 3'-UTR of mTOR was identified using the Dual-Luciferase Reporter Gene System. The direct effect of MIRNA144 on the mTOR/PTEN/PI3K/Akt pathway was determined by real-time RT-PCR and western blotting. Apoptosis of PC-3 cells induced by AX2 was determined by MTT and flow cytometry. The results indicated that mTOR/PTEN/PI3K/Akt were decreased and PTEN was increased by AX (1, 10 µmol/l) at protein and mRNA levels in a dose-dependent manner. MiRNA144 was decreased, whereas MiRNA126 was increased by AX2. MiRNA144 associated with 3'-UTR of mTOR was corroborated. Overexpression of MiRNA144 decreased mTOR, but did not affect PTEN, PI3K, or Akt. The proliferation rates of AX2 on PC-3 cells were decreased. It suggests that AX2 induces apoptosis of PC-3 cells via meddling in the mTOR/PTEN/PI3K/Akt signaling pathway, but those effects are compounded by MiRNA144. Both AX2 and MiRNA144 intercept the signaling in different ways but cross on mTOR.