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1.
World J Urol ; 42(1): 134, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38478100

RESUMEN

OBJECTIVE: To investigate the safety and feasibility of using a novel purpose-built single-port robotic system (the SHURUI Robotic Surgical System) with deformable surgical instruments to perform retroperitoneal single-port partial nephrectomy. MATERIALS AND METHODS: A prospective study was conducted to recruit patients with a single renal tumor no more than 4 cm. Robot-assisted single-port partial nephrectomy was performed by using the novel purpose-built single-port robotic system with deformable surgical instruments. Patients' demographics, tumor characteristics, and perioperative parameters were recorded and analyzed. RESULTS: Sixteen patients were recruited to the study. The median tumor size was 2.0 cm (IQR: 1.2-2.4 cm). The median R.E.N.A.L score was 6 (IQR: 4-4.5). In 3 cases, pure single-port surgery was carried out, and all the assistance was through the robotic port. Median docking time was 15.5 min (IQR: 14.25-22.25 min). Median operating time was 148.5 min (IQR: 178-238.5 min). Median console time was 107 min (IQR: 92.75-149.75 min). Median warm ischemic time was 26.5 min (IQR: 24.5-30 min). Median blood loss was 17.5 ml (IQR: 10-50 ml). CONCLUSIONS: Retroperitoneal partial nephrectomy can be safely performed with this novel purpose-built single-port robotic system (SHURUI) with deformable surgical instruments. Further studies are needed to fully evaluate the role of this new platform.


Asunto(s)
Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Estudios Prospectivos , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Nefrectomía , Resultado del Tratamiento , Estudios Retrospectivos
2.
Cell Mol Biol Lett ; 27(1): 36, 2022 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-35562668

RESUMEN

BACKGROUND: RING finger protein 7 (RNF7) is a highly conserved protein that functions as an E3 ubiquitin ligase. RNF7 overexpression is indicated in multiple human cancers, but its role in renal cell carcinoma (RCC) and the mechanisms underlying how it regulates the initiation and progression of RCC have not been explored. METHODS: Bioinformatics analysis, quantitative reverse-transcription polymerase chain reaction (RT-PCR), and Western blot were conducted to determine the expression of RNF7 in RCC tissues and cell lines. Knockdown and overexpression experiments were performed to examine the effects of RNF7 on cell viability, apoptosis, and glycolysis in vitro and on tumor growth in nude mice in vivo. RESULTS: The elevated RNF7 expression in tumor tissues of patients with RCC was correlated with poor survival. RNF7 overexpression inhibited apoptosis and promoted glycolysis in vitro and increased tumor growth in vivo by activating the JAK/STAT3 signaling pathway by ubiquitination of SOCS1. Moreover, RNF7 overexpression affected the sensitivity of RCC cells to sunitinib. Finally, STAT3 activation was necessary for transcriptional induction of RNF7. CONCLUSION: These results demonstrate that RNF7 inhibited apoptosis, promoted glycolysis, and inhibited sunitinib sensitivity in RCC cells via ubiquitination of SOCS1, thus activating STAT3 signaling. These suggest the potential for targeting the RNF7-SOCS1/JAK/STAT3 pathway for RCC treatment.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Animales , Apoptosis , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Proliferación Celular , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Glucólisis , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Masculino , Ratones , Ratones Desnudos , Factor de Transcripción STAT3/metabolismo , Sunitinib/farmacología , Proteína 1 Supresora de la Señalización de Citocinas/genética , Proteína 1 Supresora de la Señalización de Citocinas/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/genética , Ubiquitina-Proteína Ligasas
3.
BMC Cancer ; 21(1): 841, 2021 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-34284744

RESUMEN

BACKGROUND: The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. METHODS: The mRNA levels of TRIM27 and Kaplan-Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. RESULTS: We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. CONCLUSIONS: Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.


Asunto(s)
Carcinoma de Células Renales/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Renales/genética , Inhibidor NF-kappaB alfa/genética , FN-kappa B/genética , Proteínas Nucleares/metabolismo , Animales , Apoptosis/fisiología , Carcinoma de Células Renales/patología , Proliferación Celular/fisiología , Humanos , Neoplasias Renales/patología , Ratones , Ratones Desnudos , Persona de Mediana Edad , Inhibidor NF-kappaB alfa/metabolismo
4.
Nanomedicine ; 34: 102370, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33713859

RESUMEN

Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with poor prognosis. Therapeutic drugs for RCC can easily develop resistance or have unignorable toxicity or limited efficiency. Here, the thermosensitive mitochondrial metabolism-interfering anticancer drug lonidamine (LND) was combined with the photothermal material polydopamine (PDA) to treat RCC. To delivery drugs accurately to RCC site, LND and PDA were loaded in stellate mesoporous silica nanoparticles (MSNs) with a large surface area and cloaked with RCC membranes (MLP@M). The results showed that MLP@M exhibited excellent tumor targeting ability. The synergistic effects of LND and PDA in MLP@M were greatly enhanced when triggered by an 808 nm laser. Moreover, the antiproliferative and tumor suppressing abilities were enhanced with good biocompatibility after MLP@M + laser treatment. Additionally, 80% of RCC tumor-bearing mice treated with MLP@M + laser did not relapse. Our study provides a potential therapeutic approach for RCC treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Indazoles/uso terapéutico , Indoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Terapia Fototérmica , Polímeros/uso terapéutico , Animales , Antineoplásicos/farmacología , Carcinoma de Células Renales/metabolismo , Humanos , Indazoles/farmacología , Indoles/farmacología , Neoplasias Renales/metabolismo , Ratones , Mitocondrias/metabolismo , Polímeros/farmacología , Dióxido de Silicio/química , Ensayos Antitumor por Modelo de Xenoinjerto
5.
World J Surg Oncol ; 19(1): 195, 2021 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-34215279

RESUMEN

BACKGROUND: To describe the techniques and outcomes of complete transperitoneal laparoscopic nephroureterectomy (CTLNU) for upper urinary tract urothelial carcinoma (UTUC) in a single position. MATERIALS AND METHODS: Those patients with localized UTUC were included, among which 50 cases had CTLNU while 48 cases had laparoscopic nephroureterectomy with open bladder cuff excision (LNOBE). The clinical data were collected and analyzed retrospectively. RESULTS: All 98 patients underwent successful procedures of radical nephroureterectomy without transferring into open surgery. No significant difference was found among baseline clinical characteristics. Compared with the LNOBE group, the CTLNU group had a shorter operative time (98.5±40.3 min vs. 132.4±60.2 min), less blood loss (60.4±20.3 ml vs. 150.6±50.2 ml), shorter length of hospital stay (5.3±2.2 days vs. 8.1±2.3 days), and shorter incision (6.3±1.2 cm vs. 11.5±3.2 cm). The disease-related outcomes such as pathological stage, tumor grade, and recurrence rate were similar between the two groups. CONCLUSIONS: The CTLNU in a single position had advantages of shorter operation time, less blood loss, and shorter incision length. This surgical technique is a more minimally invasive, simplified, and effective way to perform the radical nephroureterectomy.


Asunto(s)
Carcinoma de Células Transicionales , Laparoscopía , Uréter , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/cirugía , Humanos , Recurrencia Local de Neoplasia , Nefrectomía , Nefroureterectomía , Pronóstico , Estudios Retrospectivos , Neoplasias Ureterales/cirugía
6.
Ther Drug Monit ; 41(1): 97-101, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30520827

RESUMEN

BACKGROUND: Kidney transplant recipients on long-term cyclosporine (CsA) therapy may develop multiple adverse drug events, and immunosuppression conversion from CsA to tacrolimus (Tac) is an option. Genetic variations, especially cytochrome P450 (CYP) 3A5*3, affects Tac dosing. However, little information is available to guide the conversion with regards to patients' pharmacogenomics. We aimed to investigate whether CYP3A5, CYP3A4, and ABCB1 genotyping could contribute to a more precise and individualized initial dosing of Tac at the time of immunosuppressant conversion. METHODS: Genotypes of 5 candidate genes (CYP3A5*3, CYP3A4*1G, ABCB1C1236T, ABCB1C3435T, and ABCB1G2677T/A) were investigated by polymerase chain reaction and restriction fragment-length polymorphism methods in 46 adult kidney transplant recipients requiring immunosuppressant conversion from CsA to TAC. Associations between these functional genetic polymorphisms and the dose-adjusted trough concentrations of CsA and Tac were evaluated, retrospectively. RESULTS: Based on the linear regression analysis, CYP3A5 expressers (*1/*1 and *1/*3) had lower Tac dose-adjusted trough concentrations on days 7, 14, 21, and 28, and they required 1.40- to 1.75-fold higher daily dose to reach the target concentration compared with nonexpressers (*3/*3) on day 28 [0.07 (0.06-0.09) mg/kg/d versus 0.05 (0.02-0.06) mg/kg/d, P = 0.001]. CYP3A4*1G or ABCB1 genetic polymorphisms had no effect on the Tac dose-adjusted trough concentrations. CONCLUSIONS: Our preliminary study supports the use of CYP3A5 genotyping to guide the initial dosing of Tac when converting the immunosuppression therapy from CsA to Tac.


Asunto(s)
Ciclosporina/uso terapéutico , Citocromo P-450 CYP3A/genética , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Adulto , Femenino , Genotipo , Humanos , Trasplante de Riñón/métodos , Masculino , Polimorfismo Genético/genética , Estudios Retrospectivos , Receptores de Trasplantes
7.
Front Oncol ; 13: 1102623, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37035174

RESUMEN

Background: Clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT) have poor prognosis. We aimed to reveal features of ccRCC with VTT and develop a urine-based prognostic classifier to predict ccRCC prognosis through integrative analyses of transcriptomic landscape and urinary signature. Methods: RNA sequencing was performed in five patients with ccRCC thrombus-tumor-normal tissue triples, while mass spectrometry was performed for urine samples from 12 ccRCC and 11 healthy controls. A urine-based classifier consisting of three proteins was developed to predict patients' survival and validated in an independent cohort. Results: Transcriptomic analysis identified 856 invasion-associated differentially expressed genes (DEGs). Furthermore, proteomic analysis showed 133 differentially expressed proteins (DEPs). Integration of transcriptomic landscape and urinary signature reveals 6 urinary detectable proteins (VSIG4, C3, GAL3ST1, TGFBI, AKR1C3, P4HB) displaying abundance changes consistent with corresponding genes in transcriptomic profiling. According to TCGA database, VSIG4, TGFBI, and P4HB were significantly overexpressed in patients with shorter survival and might be independent prognostic factors for ccRCC (all p<0.05). A prognostic classifier consisting of the three DEPs highly associated with survival performed satisfactorily in predicting overall survival (HR=2.0, p<0.01) and disease-free survival (HR=1.6, p<0.001) of ccRCC patients. The ELISA analysis of urine samples from an independent cohort confirmed the satisfied predictive power of the classifier for pathological grade (AUC=0.795, p<0.001) and stage (AUC=0.894, p<0.001). Conclusion: Based on integrative analyses of transcriptomic landscape and urinary signature, the urine-based prognostic classifier consisting of VSIG4, TGFBI, and P4HB has satisfied predictive power of ccRCC prognosis and may facilitate ccRCC molecular subtyping and treatment.

8.
Transl Androl Urol ; 12(11): 1638-1644, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38106687

RESUMEN

Background: Urologists still encounter challenges when it comes to the surgical management of tumors located on the posterior lip and posterior renal hilar region. We propose a trans-retro-peritoneal (TRP) technique to address the difficulties associated with posterior hilar tumors during retroperitoneal laparoscopic partial nephrectomy (LPN). Its efficacy was evaluated in a retrospective case-control study. Methods: The patients with posterior hilar tumors (≤7 cm) that underwent retroperitoneal LPN were included. The TRP technique allowed the posterior hilar tumor completely visible by incising the ventral peritoneum and rotating kidney ventrally during retroperitoneal LPN, which was applied in 36 cases, while the conventional retroperitoneal LPN was performed in 22 cases. Perioperative data were analyzed to evaluate the efficacy of TRP-LPN. Results: In TRP-LPN group, the TRP technique was successfully performed in all the patients without converting to open surgery or radical nephrectomy. The warm ischemia time was significantly shorter in TRP-LPN group than conventional LPN group (20.3 vs. 28.5 min, P<0.001). Furthermore, the mean estimated blood loss in TRR-LPN group was significantly less than that in conventional LPN group (86.5 vs. 90.9 mL, P<0.05). The mean operation time and recovery time of gastrointestinal function were similar between two groups. No severe complications occurred, and no positive surgical margin was found. The rate of Trifecta achievement was 50.0% (18/36) and 31.8% (7/22) respectively for TRP-LPN and conventional LPN (P=0.175). After mean follow-up of 21 months, no recurrence or metastasis occurred in all cases. Conclusions: Our findings, as demonstrated by the Trifecta outcomes, support the feasibility and efficacy of TRP-LPN in managing posterior renal hilar tumors. This approach may be considered as an efficient option for surgical management of such tumors.

9.
Transl Androl Urol ; 12(1): 90-96, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36760872

RESUMEN

Background: Laparoendoscopic single-site (LESS) surgery is performed to further narrow the incisions and reduce tissue injury. It has been more than10 years since the surgery was first described. However, there is still no report on the results of 10-year follow-up. This study evaluated the use of long-term oncology and the renal outcomes of LESS radical nephrectomy (LESS-RN) in the treatment of localized renal cancer. Methods: We retrospectively analyzed the clinical data of patients treated with LESS-RN at Changhai Hospital from 2009 to 2012. Patients with localized kidney cancer who were followed-up for at least 10 years were included in the study. The baseline data and major perioperative outcome variables were analyzed. Overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method. Results: A total of 48 patients were included in the study, which had a median follow-up of 11 years (interquartile range, 10.7-11.8 years). The 10-year OS and CSS rates were 87.5% [42/48; 95% confidence interval (CI): 0.778-0.972] and 97.9% (47/48; 95% CI: 0.937-1.021), respectively. At the most recent follow-up, there were 5 patients with a chronic kidney disease stage ≥3. Among these 5 patients, 3 developed uremia and required continuous dialysis. Conclusions: For localized renal cancer, LESS-RN is safe and effective with excellent long-term oncology controllability and good functional outcomes. Prospective studies with large sample sizes need to be conducted to validate our results.

10.
Sci Rep ; 13(1): 9778, 2023 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-37328520

RESUMEN

Clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is associated with poor prognosis. Our integrative analyses of transcriptome and proteome reveal distinctive molecular features of ccRCC with VTT, and yield the development of a prognostic classifier to facilitate ccRCC molecular subtyping and treatment. The RNA sequencing and mass spectrometry were performed in normal-tumor-thrombus tissue triples of five ccRCC patients. Statistical analysis, GO and KEGG enrichment analysis, and protein-protein interaction network construction were used to interpret the transcriptomic and proteomic data. A six-gene-based classifier was developed to predict patients' survival using Cox regression, which was validated in an independent cohort. Transcriptomic analysis identified 1131 tumorigenesis-associated differentially expressed genes (DEGs) and 856 invasion-associated DEGs. Overexpression of transcription factor EGR2 in VTT indicated its important role in tumor invasion. Furthermore, proteomic analysis showed 597 tumorigenesis-associated differentially expressed proteins (DEPs) and 452 invasion-associated DEPs. The invasion-associated DEPs showed unique enrichment in DNA replication, lysine degradation, and PPAR signaling pathway. Integration of transcriptome and proteome reveals 142 tumorigenesis-associated proteins and 84 invasion-associated proteins displaying changes consistent with corresponding genes in transcriptomic profiling. Based on their different expression patterns among normal-tumor-thrombus triples, RAB25 and GGT5 were supposed to play a consistent role in both tumorigenesis and invasion processes, while SHMT2 and CADM4 might play the opposite roles in tumorigenesis and thrombus invasion. A prognostic classifier consisting of six DEGs (DEPTOR, DPEP1, NAT8, PLOD2, SLC7A5, SUSD2) performed satisfactorily in predicting survival of ccRCC patients (HR = 4.41, P < 0.001), which was further validated in an independent cohort of 40 cases (HR = 5.52, P = 0.026). Our study revealed the transcriptomic and proteomic profiles of ccRCC patients with VTT, and identified the distinctive molecular features associated with VTT. The six-gene-based prognostic classifier developed by integrative analyses may facilitate ccRCC molecular subtyping and treatment.


Asunto(s)
Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Trombosis , Humanos , Carcinogénesis , Carcinoma de Células Renales/patología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Renales/patología , Pronóstico , Proteoma/genética , Proteómica , Transcriptoma
11.
Asian J Urol ; 10(4): 467-474, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38024423

RESUMEN

Objective: This prospective single-arm clinical trial aimed to evaluated the feasibility and safety of the application of the SHURUI system (Beijing Surgerii Technology Co., Ltd., Beijing, China), a novel purpose-built robotic system, in single-port robotic radical prostatectomy. Methods: Sixteen patients diagnosed with prostate cancer were prospectively enrolled in and underwent robotic radical prostatectomy from October 2021 to August 2022 by the SHURUI single-port robotic surgical system. The demographic and baseline data, surgical, oncological, and functional outcomes as well as follow-up data were recorded. Results: The mean operative time was 226.3 (standard deviation [SD] 52.0) min, and the mean console time was 183.4 (SD 48.3) min, with the mean estimated blood loss of 116.3 (SD 90.0) mL. The mean length of postoperative hospital stay was 4.50 (SD 0.97) days. Two patients had postoperative complications (Clavien-Dindo Grade II), and both patients improved after conservative treatment. All patients' postoperative prostate-specific antigen levels decreased to below 0.2 ng/mL 1 month after discharge. The mean prostate-specific antigen level further decreased to a mean of 0.0219 (SD 0.0641) ng/mL 6 months after surgery. Thirty days postoperatively, 12 out of 16 patients reported using no more than one urinary pad per day, and all patients reported satisfactory urinary control without the need for pads 6 months after surgery. Conclusion: The SHURUI system is safe and feasible in performing radical prostatectomy via both transperitoneal and extraperitoneal approaches. Tumor control and urinary continence were satisfying for patients enrolled in. The next phase involves conducting a large-scale, multicenter randomized controlled trial to thoroughly assess the effectiveness and safety of the new technology in a broader population.

12.
Transl Androl Urol ; 11(12): 1645-1654, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36632158

RESUMEN

Background: Patients with clinical T1-2 renal cell carcinoma (RCC) upstaging to pathological T3 showed worse survival prognosis than those without upstaging. We aimed to develop and validate a morphology-based nephrometry scoring system for predicting pathological upstaging to T3 of RCC. Methods: We retrospectively reviewed 200 patients with clinical T1-2 RCC who underwent surgical treatment. The nephrometry scores were measured through preoperative computed tomography images. The risk factors of pathological upstaging were identified by logistic regression models. The predictive accuracy of a novel morphology-based nephrometry scoring system (M-Index), was compared with R.E.N.A.L (radius, exophytic/endophytic, nearness, anterior/posterior, location), PADUA (preoperative aspects and dimensions used for an anatomic classification), DAP (diameter, axial, polar) and C-Index scores. Results: The upstaging rate of the population was 17% (34 out of 200 patients). The upstaging and non-upstaging groups were comparable in terms of age, gender ratio, body mass index, tumor laterality, and pathological type, while the upstaging group tended to have large tumor diameter, irregular tumor morphology, inner tumor location, and short polar and axial distance. Large tumor diameter refers to larger than 5 cm, while irregular tumor morphology refers to not regular shapes such as round, oval, or lobular. Univariate and multivariate logistic regression analyses showed that tumor morphology [odds ratio (OR) 3.26, 95% confidence interval (CI): 1.79-5.97] and tumor rim location (OR 2.95, 95% CI: 1.16-7.46) were independent risk factors for pathological upstaging. The receiver operating characteristic curve and decision curve analysis (DCA) demonstrated the novel M-Index based on tumor morphology and rim location outperformed R.E.N.A.L, PADUA, DAP, and C-Index in the prediction of pathological upstaging (area under curve 0.756 vs. 0.728 vs. 0.641 vs. 0.661 vs. 0.743). Conclusions: Consisting of fewer non-complex parameters, the M-Index is an intuitive and practical tool with satisfactory predictive power for pathological upstaging to T3 in RCC patients undergoing surgery.

13.
Sci Adv ; 7(5)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33571129

RESUMEN

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.


Asunto(s)
Sistemas CRISPR-Cas , Sarcoma , Proteínas Reguladoras de la Apoptosis/metabolismo , Sistemas CRISPR-Cas/genética , Humanos , Células Madre Neoplásicas/metabolismo , Proteínas Represoras/metabolismo , Sarcoma/tratamiento farmacológico , Sarcoma/genética
14.
Theranostics ; 10(4): 1619-1632, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32042326

RESUMEN

Until recently, there have been limited options for patients with bone metastatic castration-resistant prostate cancer (BmCRPC) following the failure of or development of resistance to docetaxel (DTX), which is one of the frontline treatments. Sterol regulatory element-binding protein 1 (SREBP1) is reported to regulate abnormal lipid metabolism and to promote the progression and metastasis of prostate cancer (PCa). The siRNA interferes SREBP1 may provide an efficient treatment when combined with DTX. Methods: In this study, lipoic acid (LA) and cross-linked peptide-lipoic acid micelles were cross-linked (LC) for DTX and siSREBP1 delivery (LC/D/siR). Then, cell membrane of PCa cells (Pm) and bone marrow mesenchymal stem cells (Bm) were fused for cloaking LC/D/siR (PB@LC/D/siR). Finally, the synthesized PB@LC/D/siR was evaluated in vitro and in vivo. Results: PB@LC/D/siR is internalized in PCa cells by a mechanism of lysosome escape. Tumor targeting and bone homing studies are evaluated using bone metastatic CRPC (BmCRPC) models, both in vitro and in vivo. Moreover, the enhanced anti-proliferation, anti-migration and anti-invasion capacities of DTX- and siSREBP1- loaded PB@LC (PB@LC/D/siR) were observed in vitro. Furthermore, PB@LC/D/siR was able to suppress the growth of the tumor effectively with deep tumor penetration, high safety and good protection of the bone at the tumor site. Additionally, the mRNA levels and protein levels of SREBP1 and SCD1 were able to be significantly downregulated by PB@LC/D/siR. Conclusion: This study presented a bone-cancer dual-targeting biomimetic nanodelivery system for bone metastatic CRPC.


Asunto(s)
Neoplasias Óseas/secundario , Docetaxel/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , ARN Interferente Pequeño/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Animales , Biomimética/métodos , Neoplasias Óseas/tratamiento farmacológico , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Regulación hacia Abajo , Sistemas de Liberación de Medicamentos/métodos , Resistencia a Antineoplásicos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Micelas , Nanomedicina/métodos , Neoplasias de la Próstata Resistentes a la Castración/complicaciones , Ratas , Ratas Sprague-Dawley , Ácido Tióctico/administración & dosificación , Moduladores de Tubulina/administración & dosificación , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/uso terapéutico
15.
Int J Clin Exp Pathol ; 7(6): 2883-93, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25031707

RESUMEN

Early growth response gene-1 (Egr1) has a crucial function in the development and progression of prostate cancer. However, whether Egr1 contributes to the transition of advanced androgen-independent prostate cancer (AIPC) from androgen-dependent prostate cancer (ADPC) remains largely unknown. To the best of our knowledge, through immunohistochemical staining methods, we were the first to identify that Egr1 is more highly expressed in AIPC clinical specimens than in androgen-dependent prostate cancer (ADPC). An in vitro study with quantitative RT-PCR and Western blot demonstrated that Egr1 also has a higher expression in androgen-independent PC3 cells than in the androgen-dependent LNCaP cells. Egr1 expression in LNCaP cells was significantly upregulated during the androgen deprivation treatment (ADT) and was re-downregulated through the addition of dihydrotestosterone. Although no variation in PC3 cells was identified, Egr1 responded to dihydrotestosterone and flutamide in the androgen receptor (AR)-transfected PC3 cells. Further investigation with Egr1 agonist and specific siRNA-targeting Egr1 revealed that Egr1 upregulation or downregulation was accompanied by a change in inhibitors of differentiation and DNA binding-1 (Id1) in the same direction in both LNCaP and PC3 cells. The variation is shown to be negatively regulated by androgen through AR during ADT. Our data suggested that upregulated Egr1 might partially contribute to the emergence of AIPC after prolonged ADT. This study also elucidated the potential mechanism underlying Id1 participation in the progression of prostate cancer. Understanding the key molecular events in the transition from ADPC to AIPC may provide new therapeutic intervention strategies for patients with AIPC.


Asunto(s)
Antineoplásicos Hormonales/farmacología , Proteína 1 de la Respuesta de Crecimiento Precoz/biosíntesis , Proteína 1 Inhibidora de la Diferenciación/biosíntesis , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/metabolismo , Anciano , Anciano de 80 o más Años , Western Blotting , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/tratamiento farmacológico , ARN Interferente Pequeño , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Regulación hacia Arriba
16.
Urology ; 80(1): e1-2, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22607944

RESUMEN

Laparoscopic radical nephrectomy should be executed under the most fundamental principle of early ligature of the renal artery to prevent diffusion of cancerous cells. This is extremely true in the treatment of large renal tumors touching the main renal vasculature. Obviously, the concomitance of a duplicated inferior vena cava (IVC) with associated aberrant tributaries will significantly increase the surgical difficulty and the procedural risk of vascular injury. Herein we describe a transperitoneal left laparoscopic radical nephrectomy for a large hilar left renal tumor in the presence of a duplicated IVC with complicated anomalous tributaries by a transmesocolic approach.


Asunto(s)
Laparoscopía/métodos , Nefrectomía/métodos , Vena Cava Inferior/anomalías , Vena Cava Inferior/cirugía , Humanos , Masculino , Persona de Mediana Edad
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