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Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer genesis and progression, including prostate cancer. Large amount of lncRNAs have been found that differentially expressed between prostate cancer tissues and normal prostate tissues. Whether these lncRNAs could serve as a novel biomarker for prostate cancer diagnosis or prognosis, and their biological functions in prostate cancer need further investigation. In the present study, we identified that lncRNA lnc-MX1-1 is over-expressed in prostate cancer tissues compared with their adjacent normal prostate tissues by gene expression array profiling. The expression of lnc-MX1-1 in 60 prostate cancer cases was determined by real-time quantitative PCR and the correlations between lnc-MX1-1 expression and patients' clinical features were further analyzed. Next, we impaired lnc-MX1-1 expression using RNAi in LNCaP and 22Rv1 prostate cancer cells to explore the effects of lnc-MX1-1 on proliferation and invasiveness of the cells. Our results showed that there was a significant association between over-expression of lnc-MX1-1 and patients' clinical features such as PSA, Gleason score, metastasis, and recurrence free survival. Moreover, knockdown of lnc-MX1-1 reduced both proliferation and invasiveness of LNCaP and 22Rv1 cells. In conclusion, the results suggest that lnc-MX1-1 may serve as a potential biomarker and therapeutic target for prostate cancer.
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Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Longo não Codificante/metabolismo , Proliferação de Células , Humanos , Masculino , Invasividade Neoplásica , Regulação para CimaRESUMO
Two-micrometer thulium laser resection of the prostate-tangerine technique (TmLRP-TT) has been introduced as a minimally invasive treatment for benign prostatic hyperplasia (BPH). Acute urinary retention (AUR) is a common and serious complication of BPH. The study was undertaken to assess the clinical efficacy and safety of TmLRP-TT in the treatment of patients with AUR secondary to BPH. A prospective evaluation of 52 patients undergoing TmLRP-TT from December 2011 to November 2012 was carried out. Preoperative status, surgical details, and perioperative complications were recorded. The follow-up outcome was evaluated with subjective and objective tests at 1 and 6 months. Mean age was 70.3 ± 7.8 years old. Mean prostate volume was 69.6 ± 31.6 ml, and mean residual volume with retention was 274.5 ± 150.7 ml. Mean operative time was 64.1 ± 30.4 min. Mean catheterization duration was 5.4 ± 1.1 days. The mean International Prostate Symptom Score, quality of life score, and postvoid residual urine volume decreased significantly at 6-month follow-up (21.6 ± 6.8 vs. 6.8 ± 3.2, 4.4 ± 1.2 vs. 0.9 ± 0.8, 274.5 ± 150.7 vs. 40.6 ± 22.5 ml). The mean maximum urinary flow rate was 18.7 ± 6.9 ml/s postoperative. Two (3.8 %) of the patients required blood transfusion in operation. Five (9.6 %) of the patients had transient hematuria postoperative, and two (3.8 %) of them received 3 days recatheterization due to clot retention. The early clinical results suggest that the TmLRP-TT is a promising safe, effective, and minimally invasive treatment for patients with AUR secondary to BPH. The incidence of complications was low.
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Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática/complicações , Retenção Urinária/cirurgia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Retenção Urinária/etiologiaRESUMO
Thulium laser resection of the prostate-tangerine technique (TmLRP-TT) dissects whole prostatic lobes off the surgical capsule, similar to peeling a tangerine. The present study aimed to evaluate the safety and efficacy of TmLRP-TT for older symptomatic benign prostatic hyperplasia patients with large prostates during 18 months of follow-up. A prospective analysis of 95 consecutive patients with large prostates (>80 ml) who underwent surgical treatment using TmLRP-TT was carried out. All patients were evaluated preoperatively and at 1, 6, 12, and 18 months postoperatively by the International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Q max), postvoid residual urine volume (PVR), International Index of Erectile Function 5 (IIEF-5), urine analysis, and urine culture. Perioperative complications were recorded and graded by the modified Clavien classification system (CCS). Mean preoperative prostate volume was 106.81 ± 24.79 ml. TmLRP-TT was successfully completed in all patients. The mean operative duration, catheterization time, and hospital stay were 95.36 ± 27.06 min, 2.25 ± 0.9 days, and 5.39 ± 1.18 days, respectively. The decrease in mean hemoglobin level was 1.23 ± 0.72 g/dl, and that in mean serum sodium level was 0.71 ± 2.56 mmol/l. Within the observation period of 18 months, the patients showed an improvement in IPSS (20.01 ± 7.08 vs. 4.96 ± 3.68), QoL (4.10 ± 1.16 vs. 1.23 ± 1.30), Q max (8.14 ± 3.81 ml/s vs. 18.33 ± 2.56 ml/s) and PVR (102.70 ± 70.64 ml vs. 20.28 ± 30.02 ml), compared with baseline values (P < 0.001). IIEF-5 remained stable. Minor complications occurred in 10 (10.52 %) of 95 patients (Clavien grade 1, 9.47 % and grade 2, 1.05 %). There were no severe complications requiring reintervention (Clavien grade 3, 0 % and grade 4, 0 %). TmLRP-TT is a safe and effective surgical endoscopic technique associated with a low complication rate in large prostates as assessed during an 18-month follow-up period. It is a promising technology, which may be considered as one of the alternatives to open simple prostatectomy (OP) for large prostates in the future.
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Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers , Próstata/patologia , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Túlio/uso terapêutico , Idoso , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Cuidados Pré-Operatórios , Estudos Prospectivos , Prostatectomia/efeitos adversos , Hiperplasia Prostática/fisiopatologia , Resultado do Tratamento , MicçãoRESUMO
Men with azoospermia or severe oligospermia (< 5 x 10(6)/ml) should have genetic testing to identify the reason for male infertility before treatment. Identification of obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is essential because genetic testing differs for OA (which has normal testicular function, testicular volume, and FSH) versus NOA (which has small, soft testes and increased FSH). Among patients with NOA, history and physical examination along with laboratory testing is required to choose genetic testing specifically for primary testicular failure or congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with OA due to congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be indicated if patient has severe oligospermia or NOA. These genetic tests help to identify which patients may benefit from medical and/or surgical intervention. The most recent techniques for genetic analysis will improve diagnosis and management of male infertility.
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Infertilidade Masculina/genética , Testes Genéticos , Humanos , Masculino , Oligospermia/genéticaRESUMO
Male infertility microsurgery represents the fastest growing sub-specialty in urology and clinical andrology over the past two decades. The importance of microsurgery for male infertility has risen as a part of the urologist's armamentarium in the medical and surgical management of male infertility. Despite the advances in male infertility microsurgery in China, the lack of standardized and well-organized training programs for male infertility microsurgery remains a serious problem affecting its development. In this article, Zhao and Peng have shared their experience with the learning curve of male infertility microsurgery at the Center for Male Reproductive Medicine and Microsurgery, Weill Medical College of Cornell University, which centers on how to pay attention to the details and basic principles of microsurgery. Male infertility microsurgery is physically, technically and mentally challenging, and must be first learned in the laboratory. Clinical success depends heavily upon appropriate training in a microsurgical laboratory. Good training can significantly reduce operation time and surgical errors as well as improve the quality of outcomes.
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Andrologia/educação , Infertilidade Masculina/cirurgia , Microcirurgia/educação , Humanos , MasculinoRESUMO
OBJECTIVE: To evaluate the clinical efficiency and safety of two-micron laser resection of the prostate-tangerine technique (TmLRP-TT) for the treatment of large-volume ( > 70 ml) prostate in patients with benign prostatic hyperplasia (BPH). METHODS: This retrospective analysis included 80 BPH patients with the prostatic volume larger than 70 ml, all treated by TmLRP-TT. We comparatively analyzed the levels of hemoglobin and serum sodium before and after surgery, recorded intra- and post-operative com- plications, and followed up the patients at 6 and 12 months after operation for International Prostate Symptom Score (IPSS), quality of life (QOL), maximum flow rate (Qmax), and postvoid residual urine volume (PVR). RESULTS: All the operations were successfully completed. The mean hemoglobin decreased (0.68 +/- 0.43) g/dl intraoperatively, but no apparent reduction was observed in serum sodium. Lower urinary tract symptoms were relieved significantly in all the cases. At 12 months after surgery, IPSS was decreased by 73.89% as compared with the baseline (20.03 +/- 6.9 vs 5.23 +/- 3.59), QOL by 64.55% (4.09 +/- 1.19 vs 1.45 +/- 1.36), and PVR by 79.30% (97.31 +/- 57.90 vs 20.14 +/- 24.20 ml), while Qmax increased by 140.42% ([8.04 +/- 3.62] vs [19.33 +/- 3.28] ml/s). The incidence of complications was low either intraoperatively or during the 12 months after operation. CONCLUSION: TmLRP-TT is a safe and effective surgical endoscopic approach to the treatment of large-volume prostate in BPH patients.
Assuntos
Terapia a Laser/métodos , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Increasingly accumulated results from randomized controlled trials and other clinical studies have demonstrated that male circumcision reduces the risks of acquisition and transmission of HIV, HPV, HSV-2, and other sexually transmitted infections, and thus has a potential role in preventing cervical cancer, penile cancer and prostate cancer. The prevalence of male circumcision in China is currently less than 5%. The clinical evaluation studies and randomized controlled trials of the Shang Ring device showed excellent safety profiles, extremely high acceptability, and satisfaction among the participants and service providers in Africa and China. Given the recent recommendations by the World Health Organization and the Joint United Nations Program on HIV/AIDS (UNAIDS), voluntary medical male circumcision should be promoted in China at the national level as an important alternative intervention to reduce reproductive tract infections and prevent both males and females from reproductive tract cancers. More emphasis is required on the studies of the long-term health benefits of male circumcision in uro-andrology.
Assuntos
Circuncisão Masculina , Neoplasias Penianas/prevenção & controle , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Urinárias/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , China , Feminino , Infecções por HIV/prevenção & controle , Humanos , Masculino , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Organização Mundial da SaúdeRESUMO
Male infertility is a common and complex disease in urology and andrology, and for many years there has been no effective surgical treatment. With the emergence of microsurgery and assisted reproductive medicine (IVF/ICSI), rapid development has been achieved in the treatment of male infertility. The Center for Male Reproductive Medicine and Microsurgery at Weill Cornell Medical College of Cornell University has been playing an important leading role in developing microsurgical techniques for the management of male infertility. The development of microsurgical treatment of male infertility in China has experienced the 3 periods of emerging, making, and boosting ever since its systematic introduction from Weill Cornell Medical College 15 years ago. At present, many Chinese hospitals have adopted microsurgery in the management of male infertility, which has contributed to the initial establishment of a microsurgical treatment system for male infertility in China. However, some deficiencies do exist concerning microsurgical treatment of male infertility, as in normalized technical training programs for competent surgeons, unified criteria for evaluation of surgical outcomes, and detailed postoperative follow-up data. This article presents an overview on the 15-year development of microsurgical management of male infertility in China, points out the existing deficiencies, and offers some propositions for the promotion of its development.
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Infertilidade Masculina/cirurgia , Microcirurgia , China , Humanos , MasculinoRESUMO
In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress-strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.
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OBJECTIVE: To evaluate the long-term efficacies and complications of thulium laser resection of prostate-tangerine technique (TmLRP-TT) in the treatment of benign prostatic hyperplasia (BPH). METHODS: From November 2004 to December 2009, a total of 348 BPH patients undergoing TmLRP-TT at our hospital were evaluated retrospectively for long-term efficacies and complications. The follow-up data included international prostate symptom score (IPSS), quality of life score (QOL), maximum urinary flow (Qmax) and post void urinary residual (PVR). RESULTS: After 4 years, IPSS decreased 70% (22.7 ± 7.7 vs 6.8 ± 5.1) , QOL decreased 65% (4.3 ± 0.7 vs 1.5 ± 1.0), Qmax increased 212% (6.0 ± 2.6 ml/s vs 18.7 ± 4.6 ml/s) and PVR decreased 83% (104.7 ± 34.3 ml vs 17.7 ± 10.7 ml). Cumulative incidences of long-term complications was 6.0% (n = 21), including a second TmLRP-TT due to BPH recurrence (n = 4, 1.2%), urethral stricture (n = 8, 2.3%) and bladder neck contracture (n = 9, 2.6%). Overall, 93% were satisfied with surgical outcomes. CONCLUSION: TmLRP-TT has excellent efficacies with a low rate of long-term complications. Most patients are satisfied with surgical outcomes.
Assuntos
Hiperplasia Prostática/cirurgia , Túlio/uso terapêutico , Ressecção Transuretral da Próstata/métodos , Idoso , Idoso de 80 Anos ou mais , Humanos , Lasers de Estado Sólido , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Stepwise mini-incision microdissection testicular sperm extraction (mTESE) is a procedure that attempts to minimize testicular damage. However, the mini-incision approach may vary in patients with different etiologies. Here, we performed a retrospective analysis of 665 men with nonobstructive azoospermia (NOA) who underwent stepwise mini-incision mTESE (Group 1) and 365 men who underwent standard mTESE (Group 2). The results showed that the operation time (mean ± standard deviation) for patients with successful sperm retrieval in Group 1 (64.0 ± 26.6 min) was significantly shorter than that in Group 2 (80.2 ± 31.3 min), with P <0.001. The total sperm retrieval rate (SRR) was 23.1% in our study, and there was no significant difference between Group 1 and Group 2 ( P >0.05), even when the etiologies of NOA were taken into consideration. The results of consecutive multivariate logistic regression analysis (odds ratio [OR]: 0.57; 95% confidence interval [CI]: 0.38-0.87; P =0.009) and receiver operating characteristic (ROC) analysis (area under the ROC curve [AUC]=0.628) showed that preoperative anti-Müllerian hormone (AMH) level in idiopathic NOA patients was a potential predictor for surgical outcomes after initial three small incisions made in the equatorial region without sperm examined under an operating microscope (Steps 2-4). In conclusion, stepwise mini-incision mTESE is a useful technique for NOA patients, with comparable SRR, less surgical invasiveness, and shorter operation time compared with the standard approach. Low AMH levels may predict successful sperm retrieval in idiopathic patients even after a failed initial mini-incision procedure.
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Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Assuntos
Azoospermia , Ducto Deferente , Gravidez , Feminino , Humanos , Masculino , Ducto Deferente/cirurgia , Ducto Deferente/anormalidades , Azoospermia/cirurgia , Epididimo/cirurgia , Estudos Retrospectivos , Centros de Atenção Terciária , China , SêmenRESUMO
Although previous studies have reported a facial expression classification deficit among adults with SDB, we do not know whether these findings can be generalized to children. In our study, children with sleep-disordered breathing (SDB) were divided into three groups: primary snoring (n = 51), mild obstructive sleep apnea (OSA) (n = 39), and moderate/severe OSA (n = 26). All participants, including 20 healthy controls, underwent an overnight polysomnography recording and the Emotional Expression Recognition Task. Psychosocial problems were evaluated using the parent-reported Strengths and Difficulties Questionnaire (SDQ). There was a borderline significant interaction between expression category and group on reaction times. Further analysis revealed that positive classification advantage (PCA) disappeared in the moderate/severe OSA group, whereas it persisted in the control, primary snoring, and mild OSA groups. Emotional symptoms were positively correlated with OAHI. In both the happy and sad conditions, RT was negatively related to age and body mass index (BMI) but was independent of the obstructive apnea-hypopnea index (OAHI), arterial oxygen (SaO2) and total sleep time. The accuracy of identifying a sad expression was negatively related to conduct problems. Children with moderate/severe OSA exhibited dysfunction in facial expression categorization, which could potentially affect social communication ability.
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In current studies of safety assessment for complex systems with the evidential reasoning (ER) rule, the evidence reliability is generally given by experts, which makes the observation data by sensors ignored. However, sensors are inevitably affected by such various uncertainties as perturbations in engineering practice, which can reduce their quality and tracking ability. As such, the observation data may become unreliable, and the modeling accuracy of the ER rule is decreased. In this article, a new ER rule-based safety assessment method with sensor reliability for complex systems is proposed, where sensor reliability and perturbation are considered. The coefficient of the variation-based weighting (CVBW) method is employed to obtain sensor weight. The sensor reliability is calculated by static reliability and dynamic reliability, which are determined by experts and the distance-based method, respectively. The perturbation is quantified as a bounded parameter defined as the perturbation factor, which is used to describe uncertainties and aggregate static reliability and dynamic reliability. The performance analysis of safety assessment is conducted to demonstrate the rationality of perturbation and position poor sensors, followed by a safety assessment algorithm. A case study is carried out to validate the effectiveness of the proposed method.
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Algoritmos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To characterize age-related cellular phenotype alterations and growth rates of human prostatic stromal cell cultures from the normal prostatic peripheral zone of young donors (PZ-young) and old donors (PZ-old). METHODS: We isolated stromal cells from 10 donors of different ages, assessed the cellular phenotypes by immunocytostaining for prolyl-4-hydroxylase, alpha-smooth muscle actin (alpha-SMA) and desmin, and analysed the ultrastructure by transmission electron microscopy (TEM). The proliferation and apoptosis of the cells were determined by Cell Counting Kit-8 assay and flow cytometry, respectively. RESULTS: All the stromal cells were positive for prolyl-4-hydroxylase regardless of the donors' age, while alpha-SMA and desmin positive cells increased with their age. The positive expressions of alpha-SMA and desmin were (2.56 +/- 1.81)% and (0.89 +/- 0.93)% in PZ-young, and (38.89 +/- 11.22)% and (14.89 +/- 5.97)% in PZ-old (P < 0.01). The alpha-SMA- and/or desmin-positive stromal cells were morphologically large, flat and polygonal. Ultrastructural analysis showed that the cell cultures from PZ-old were richer in rough endoplasmic reticulum and golgi complexes. The stromal cells of PZ-old had a lower growth rate than that of PZ-young (P < 0.01), but there was no significant difference in the apoptosis rate between the two groups. CONCLUSION: Cellular phenotypes of human prostate stromal cell cultures change with the increase of age from predominantly typical fibroblasts to a mixture of fibroblasts and myofibroblasts, which might responsible for the high incidence of prostate cancer in elderly men.
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Próstata/citologia , Próstata/patologia , Células Estromais/citologia , Células Estromais/patologia , Adulto , Fatores Etários , Idoso , Proliferação de Células , Células Cultivadas , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Neoplasias da Bexiga Urinária/patologia , Adulto JovemRESUMO
To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml-1, 10.1-20.0 ng ml-1, and >20.0 ng ml-1, the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml-2, 0.297 ng ml-2, and 1.180 ng ml-2, respectively (sensitivity >90%). Compared with PSA, PSAD, and TZ-PSAD, the efficiency of PZ-PSAD for predicting PCa is the highest, leading to fewer missed diagnoses and unnecessary biopsies.
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Valor Preditivo dos Testes , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , China , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não ParamétricasRESUMO
The androgen receptor (AR) is expressed in prostate fibroblasts in addition to normal prostate epithelial cells and prostate cancer (PCa) cells. Moreover, AR activation in fibroblasts dramatically influences prostate cancer (PCa) cell behavior. Androgen deprivation leads to deregulation of AR downstream target genes in both fibroblasts and PCa cells. Here, we identified LIM domain only 2 (LMO2) as an AR target gene in prostate fibroblasts using ChIP-seq and revealed that LMO2 can be repressed directly by AR through binding to androgen response elements (AREs), which results in LMO2 overexpression after AR deactivation due to normal prostate fibroblasts to cancer-associated fibroblasts (CAFs) transformation or androgen deprivation therapy. Next, we investigated the mechanisms of LMO2 overexpression in fibroblasts and the role of this event in non-cell-autonomous promotion of PCa cells growth in the androgen-independent manner through paracrine release of IL-11 and FGF-9. Collectively, our data suggest that AR deactivation deregulates LMO2 expression in prostate fibroblasts, which induces castration resistance in PCa cells non-cell-autonomously through IL-11 and FGF-9.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Benzamidas/farmacologia , Fibroblastos Associados a Câncer/metabolismo , Proteínas com Domínio LIM/metabolismo , Nitrilas/farmacologia , Feniltioidantoína/farmacologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Androgênicos/metabolismo , Regulação para Cima , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sequenciamento de Cromatina por Imunoprecipitação , Fator 9 de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-11/metabolismo , Masculino , Camundongos , Comunicação Parácrina , Cultura Primária de Células , Ativação Transcricional/efeitos dos fármacosRESUMO
This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-beta1 (TGF-beta1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma-epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation.
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Adenocarcinoma/patologia , Próstata/patologia , Neoplasias da Próstata/patologia , Células Estromais/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adulto , Animais , Linhagem Celular Tumoral , Técnicas de Cocultura , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , Próstata/efeitos dos fármacos , Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Células Estromais/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Adulto JovemRESUMO
Post-translational degradation of protein plays an important role in cell life. We employed chimeric molecules (dihydrotestosterone-based proteolysis-targeting chimeric molecule [DHT-PROTAC]) to facilitate androgen receptor (AR) degradation via the ubiquitin-proteasome pathway (UPP) and to investigate the role of AR in cell proliferation and viability in androgen-sensitive prostate cancer cells. Western blot analysis and immunohistochemistry were applied to analyse AR levels in LNCaP cells after DHT-PROTAC treatment. Cell counting and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay were used to evaluate cell proliferation and viability after AR elimination in both LNCaP and PC-3 cells. AR was tagged for elimination via the UPP by DHT-PROTAC, and this could be blocked by proteasome inhibitors. Degradation of AR depended on DHT-PROTAC concentration, and either DHT or an ALAPYIP-(arg)(8) peptide could compete with DHT-PROTAC. Inhibition of cell proliferation and decreased viability were observed in LNCaP cells, but not in PC-3 or 786-O cells after DHT-PROTAC treatment. These data indicate that AR elimination is facilitated via the UPP by DHT-PROTAC, and that the growth of LNCaP cells is repressed after AR degradation.
Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores Androgênicos/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Di-Hidrotestosterona/farmacologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ubiquitina/metabolismoRESUMO
OBJECTIVE: The objective of this survey was to study the association between Helicobacter pylori infection and the severity of coronary atherosclerosis. METHODS: The study population consisted of 961 consecutive patients (711 males and 250 females) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' body mass index, blood pressure, the blood lipid, blood glucose, leukocyte count (10(9)/L), neutrophil count (10(9)/L), and Helicobacter pylori-specific IgG antibodies were performed. Coronary angiograms were scored according to vessel score and Gensini's score. RESULTS: A significant association between H. pylori infection and coronary atherosclerosis as well as its severity was not find in this cross section study (p = 0.858). And, the level distribution of vessel score (p = 0.906) and Gensini's score (p = 0.905) were similar in the seropositivity group and seronegativity group of Helicobacter pylori infection. However, the level of fasting high-density lipoprotein cholesterol (mmol/L) (p = 0.013) was significantly lower in the seropositivity group than that in the seronegativity group of Helicobacter pylori infection. CONCLUSIONS: In conclusion, in the present study, a significantly correlation between Helicobacter pylori seropositivity and angiographically evaluated severity of atherosclerosis was not find. And, the present study showed a good correlation between Helicobacter pylori infection and decreased HDL cholesterol. However, the exact mechanisms need further study.