Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
Mol Ther ; 32(4): 920-934, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38341611

RESUMO

CRISPR-Cas9 is the most commonly used genome-editing tool in eukaryotic cells. To modulate Cas9 entry into the nucleus to enable control of genome editing, we constructed a light-controlled CRISPR-Cas9 system to control exposure of the Cas9 protein nuclear localization signal (NLS). Although blue-light irradiation was found to effectively control the entry of Cas9 protein into the nucleus with confocal microscopy observation, effective gene editing occurred in controls with next-generation sequencing analysis. To further clarify this phenomenon, a CRISPR-Cas9 editing system without the NLS and a CRISPR-Cas9 editing system containing a nuclear export signal were also constructed. Interestingly, both Cas9 proteins could achieve effective editing of target sites with significantly reduced off-target effects. Thus, we speculated that other factors might mediate Cas9 entry into the nucleus. However, NLS-free Cas9 was found to produce effective target gene editing even following inhibition of cell mitosis to prevent nuclear import caused by nuclear membrane disassembly. Furthermore, multiple nucleus-localized proteins were found to interact with Cas9, which could mediate the "hitchhiking" of NLS-free Cas9 into the nucleus. These findings will inform future attempts to construct controllable gene-editing systems and provide new insights into the evolution of the nucleus and compatible protein functions.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Proteína 9 Associada à CRISPR/genética , Sinais de Localização Nuclear/genética
2.
Hum Gene Ther ; 34(3-4): 112-128, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36453226

RESUMO

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based genome editing system exhibits marked potential for both gene editing and gene therapy, and its continuous improvement contributes to its great clinical potential. However, the largest hindrance to its application in clinical practice is the presence of off-target effects (OTEs). Thus, in addition to continuous optimization of the CRISPR system to reduce and eventually eliminate OTEs, further development of unbiased genome-wide detection of OTEs is key for its successful clinical application. This article summarizes detection strategies for OTEs of different CRISPR systems, to provide detailed guidance for the detection of OTEs in CRISPR-based genome editing.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Genoma , Terapia Genética
3.
Hum Gene Ther ; 33(7-8): 358-370, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34963339

RESUMO

The clustered regularly interspaced short palindromic repeats (CRISPR) system is inarguably the most valuable gene editing tool ever discovered. Currently, three classes of CRISPR-based genome editing systems have been developed for gene editing, including CRISPR/CRISPR associate system (Cas) nucleases, base editors, and prime editors. Ever-evolving CRISPR technology plays an important role in medicine; however, the biggest obstacle to its use in clinical practice is the induction of off-target effects (OTEs) during targeted editing. Therefore, continuous improvement and optimization of the CRISPR system for reduction of OTEs is a major focus in the field of CRISPR research. This review aims to provide a comprehensive guide for optimization of the CRISPR-based genome editing system.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Endonucleases/genética
4.
Front Mol Biosci ; 7: 115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733913

RESUMO

Phenylketonuria (PKU) is a common genetic metabolic disorder that affects the infant's nerve development and manifests as abnormal behavior and developmental delay as the child grows. Currently, a triple-quadrupole mass spectrometer (TQ-MS) is a common high-accuracy clinical PKU screening method. However, there is high false-positive rate associated with this modality, and its reduction can provide a diagnostic and economic benefit to both pediatric patients and health providers. Machine learning methods have the advantage of utilizing high-dimensional and complex features, which can be obtained from the patient's metabolic patterns and interrogated for clinically relevant knowledge. In this study, using TQ-MS screening data of more than 600,000 patients collected at the Newborn Screening Center of Shanghai Children's Hospital, we derived a dataset containing 256 PKU-suspected cases. We then developed a machine learning logistic regression analysis model with the aim to minimize false-positive rates in the results of the initial PKU test. The model attained a 95-100% sensitivity, the specificity was improved 53.14%, and positive predictive value increased from 19.14 to 32.16%. Our study shows that machine learning models may be used as a pediatric diagnosis aid tool to reduce the number of suspected cases and to help eliminate patient recall. Our study can serve as a future reference for the selection and evaluation of computational screening methods.

5.
Medicine (Baltimore) ; 98(5): e14237, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30702581

RESUMO

Recent studies have confirmed the efficacy of sorafenib for patients with advanced renal cell carcinoma; however, its efficacy and safety as an adjuvant therapy in patients with non-metastatic and loco-regional renal cell carcinoma after surgery remains controversial. Thus, the aim of the present retrospective study was to evaluate the efficacy of adjuvant sorafenib therapy in such patients from 8 centers in northwestern China that were treated from August 2009 to December 2016.After surgery, the patients (n = 48) received oral sorafenib for 3 months. The control group (n = 48) comprised patients that underwent the same surgery from December 2009 to June 2016 but without adjuvant therapy who were matched 1:1 with the sorafenib group with respect to sex, age, pathological findings, disease stage and grade, operation time, and surgical procedure. The primary outcome compared between the groups was disease-free survival. Adverse events were also recorded to evaluate the safety of sorafenib. The influence of patients' characteristics and laboratory tests on recurrence was analyzed using unconditional logistic regression.Overall, the demographic characteristics of the 2 groups were similar. There was no significant difference in the rate of recurrence (8.3% for sorafenib patients and 6.2% for the matched patients, P = .66) or median disease-free survival between the 2 groups (hazard ratio = 1.561, 95% confidence interval = 0.349-6.987, P = .56). In multiple logistic regression analysis, increased blood urea nitrogen (BUN) emerged as an independent predictor of recurrence risk (P = .02).These results indicate that postoperative sorafenib adjuvant therapy did not achieve the expected beneficial effect, pointing to the need for further studies to evaluate its utility in such cases.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nefrectomia/métodos , Sorafenibe/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos
6.
BMC Cancer ; 19(1): 162, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786867

RESUMO

BACKGROUND: Metastasis in penile corpus cavernosum from esophageal squamous carcinoma is a rare but fatal disease, which was reported in cases without series studies. CASE PRESENTATION: An 84-year-old male smoker, who had a history of curative resection of esophageal squamous carcinoma 12 months before, presented with aggressive dysuria and penis pain for 1 month. Ultrasonic guided biopsy diagnosed metastatic squamous carcinoma from the primary in the esophagus. The accurately modulated conformal radiotherapy and non-steroidal antiinflammatory drugs achieved to alleviate the penis pain temporarily. But the disease progressed and disseminated in a short period. He died of multiple metastases and cancer cachexia in 4 months. CONCLUSIONS: Primary esophageal cancer metastasis to penile corpus cavernosum refers to short onset time of metastasis, extensive dissemination, bad response to treatment and poor prognosis. Palliative therapy to patients with the disease could achieve temporary local symptom relief, but not prolong survival time. More research is necessary to understand the underlying mechanism of esophagheal metastasis.


Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Cuidados Paliativos , Neoplasias Penianas/secundário , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia , Dor do Câncer/fisiopatologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Disuria/fisiopatologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/radioterapia , Pênis/diagnóstico por imagem , Pênis/fisiopatologia , Radioterapia , Doenças Raras , Fumantes , Ultrassonografia
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(1): 93-99, 2019 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-30692073

RESUMO

OBJECTIVE: To analyze the association of the clinical inflammatory indices with the severity of urinary sepsis. METHODS: We reviewed the clinical data of 70 patients with urinary sepsis treated in our hospital between January, 2013 and April, 2018. All the patients were diagnosed in line with the Guidelines for Diagnosis and Treatment of Urological Diseases in China (2014 edition), including 22 patients with sepsis, 12 with hypotension and severe sepsis, 17 with septic shock, and 19 with critical septic shock. White blood cell count (WBC), neutrophil percentage (N%), platelets (PLT), fibrinogen (FIB), Ddimer, interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP) were examined in all the cases and compared among the 4 groups. The correlations of these inflammatory markers with the severity of sepsis were analyzed using logistic regression analysis. RESULTS: The 4 groups of patients showed significant differences in N%, PLT, D-dimer, and PCT (P < 0.05) but not in CRP (P>0.05). Kruskal-Wallis Pairwise comparisons showed that the N% and PCT in patients with sepsis differed significantly from those in the other 3 groups; platelets in patients with sepsis differed significantly from those in patients with septic shock and critical septic shock; D-dimer differed significantly between patients with sepsis and those with septic shock. Among the 4 groups, the median levels of PLT decreased and PCT and N% increased with the worsening of sepsis. Logistic regression analysis indicated that PCT (r=0.186, P=0.000), N% (r=0.047, P=0.035) and PLT (r=-0.012, P=0.003) were significantly correlated with the severity of sepsis in these patients. CONCLUSIONS: PCT, PLT and N% are all significantly correlated with the severity of sepsis, and their combined detection can be informative for assessing the severity of sepsis to facilitate clinical decisions on treatment.


Assuntos
Sepse/sangue , Índice de Gravidade de Doença , Biomarcadores/sangue , Proteína C-Reativa/análise , China , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Humanos , Interleucina-6/sangue , Contagem de Leucócitos , Contagem de Plaquetas , Pró-Calcitonina/sangue , Sepse/diagnóstico , Choque Séptico/sangue , Choque Séptico/diagnóstico , Estatísticas não Paramétricas , Infecções Urinárias/diagnóstico
8.
Chin J Traumatol ; 21(6): 316-322, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30340979

RESUMO

PURPOSE: Urosepsis in adults comprises approximately 25% of all sepsis cases, and is due to complicated urinary tract infections in most cases. However, its mechanism is not fully clarified. Urosepsis is a very complicated disease with no effective strategy for early diagnosis and treatment. This study aimed to identify possible target-related proteins involved in urosepsis using proteomics and establish possible networks using bioinformatics. METHODS: Fifty patients admitted to the Urology Unit of Lanzhou General PLA (Lanzhou, China), from October 2012 to October 2015, were enrolled in this study. The patients were further divided into shock and matched-pair non-shock groups. 2-DE technique, mass spectrometry and database search were used to detect differentially expressed proteins in serum from the two groups. RESULTS: Six proteins were found at higher levels in the shock group compared with non-shock individuals, including serum amyloid A-1 protein (SAA1), apolipoprotein L1 (APOL1), ceruloplasmin (CP), haptoglobin (HP), antithrombin-III (SERPINC1) and prothrombin (F2), while three proteins showed lower levels, including serotransferrin (TF), transthyretin (TTR) and alpha-2-macroglobulin (A2M). CONCLUSION: Nine proteins were differentially expressed between uroseptic patients (non-shock groups) and severe uroseptic patients (shock groups), compared with non-shock groups, serum SAA1, APOL1,CP, HP, SERPINC1and F2 at higher levels, while TF, TTR and A2M at lower levels in shock groups.these proteins were mainly involved in platelet activation, signaling and aggregation, acute phase protein pathway, lipid homeostasis, and iron ion transport, deserve further research as potential candidates for early diagnosis and treatment. (The conclusion seems too simple and vague, please re-write it. You may focus at what proteins have been expressed and introduce more detail about its significance.).


Assuntos
Proteômica , Sepse/diagnóstico , Sepse/etiologia , Infecções Urinárias/complicações , Adulto , Idoso , Antitrombina III , Apolipoproteína L1/sangue , Ceruloplasmina , Feminino , Haptoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Pré-Albumina , alfa 2-Macroglobulinas Associadas à Gravidez , Protrombina , Sepse/sangue , Sepse/genética , Proteína Amiloide A Sérica , Transferrina
9.
Oncotarget ; 9(15): 12186-12200, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29552302

RESUMO

The current study aimed to identify a comprehensive expression-profile of microRNAs (miRNAs) in expressed prostatic secretion (EPS) collected from healthy men and patients with CP/CPPS (Chronic prostatitis/Chronic pelvic pain syndrome). After clinical screening of 382 participants, 60 healthy men and 59 IIIA CP/CPPS patients with significant pelvic-pain were included into this study from March 2012 to December 2014. High-throughput sequencing was employed to identify characteristic expression-profile of EPS-miRNAs. QRT-PCR was further performed to confirm elevated levels of differential EPS-miRNAs. Finally, candidate EPS-miRNAs were measured traceably in 21 follow-up patients and their classify-accuracy on IIIA CP/CPPS were analyzed by ROC (receiver operating characteristic) curve. In discovery-phage, 41 and 43 predominant EPS-miRNAs were found in pooled EPS-sample from 40 healthy men and 39 IIIA CP/CPPS patients, respectively. Furthermore, 22 abundant EPS-miRNAs were up-regulated with ≥ 2-fold in 20 patients compared to 20 healthy men. In testing-phage, elevated levels of miR-21-5p, miR-30a-5p, miR-30d-5p, miR-103a-3p and miR-141-3p were further confirmed in 33 patients by comparing to 30 healthy men. In validation-phage, relieved pelvic-pain symptom of 21 follow-up patients was found to be accompanied by significant down-regulation of miR-21-5p, miR-103a-3p and miR-141-3p. Particularly, ROC curve analysis indicated the highest area under ROC curve (AUC) was found for miR-21-5p (0.891), followed in order by miR-141-3p and miR-103a-3p. Our studies provided evidence that secretory miRNAs existed in EPS and dysregulated EPS-miRNAs were associated with prostatitis. In particular, miR-21-5p possessed a high classify-accuracy for IIIA CP/CPPS patients with significant pelvic pain.

10.
Zhonghua Nan Ke Xue ; 23(10): 878-882, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29727535

RESUMO

OBJECTIVE: To investigate the safety and efficacy of pancreatic kininogenase combined with sildenafil in the treatment of erectile dysfunction(ED) in type 2 diabetes mellitus (DM) patients in the high-altitude area. METHODS: This study included 93 ED patients with type 2 DM, all residents of the Xining area 1500 meters above sea level. We randomly divided them into an experimental group (n = 48) and a control group (n = 45), the former treated with pancreatic kininogenase(120 u, tid) and sildenafil (25 mg, qd at bedtime), while the latter with sildenafil only (25 mg, qd at bedtime).After 4 and 8 weeks of medication, we obtained the penile hemodynamic parameters,IIEF-5 scores, and sexual intercourse satisfaction(SIS) scores and compared them between the two groups of patients. RESULTS: There were no statistically significant differences in age or DM course between the two groups of patients (P >0.05).Compared with the baseline, both the experimental and control groups showed remarkably improvement inthe IIEF-5 score (8.81 ± 2.06 vs 11.54 ± 7.72 and 8.29 ± 1.91 vs 9.37± 1.65, P <0.05), SIS score (3.35 ± 2.43vs6.83± 2.61and 3.41 ± 2.38 vs 4.92± 2.49, P <0.05), and penile hemodynamic parameters obtained by color duplex Doppler ultrasonography(P <0.05), with significant differences between the two groups in the IIEF-5 score (11.54 ± 7.72 vs 9.37± 1.65, P <0.05) and SIS score (6.83± 2.61 vs 4.92± 2.49, P <0.05) but not in the penile hemodynamic parameters (P >0.05). Even more remarkable improvement was observed at 8 weeks in the experimental and control groups in the IIEF-5 score (19.29± 1.85 and 15.43± 1.74)(P <0.05), SIS score (11.73 ± 2.57 and 6.55± 2.71) (P <0.05), and penile hemodynamic parameters(P <0.05), all with significant differences between the two groups (P <0.05). CONCLUSIONS: Pancreatic kininogenase combined with sildenafil has a better clinical effect than sildenafil alone on ED in type 2 DM patientsin the high-altitude area.


Assuntos
Altitude , Diabetes Mellitus Tipo 2/complicações , Disfunção Erétil/terapia , Calicreínas/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Idoso , Coito , Quimioterapia Combinada , Disfunção Erétil/etiologia , Humanos , Masculino , Pâncreas/enzimologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/fisiologia , Resultado do Tratamento
11.
Exp Ther Med ; 11(6): 2139-2146, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27284295

RESUMO

The aim of the present study was to investigate the association between connexin (Cx)43 levels and alterations in gap junctional mediation of intercellular communication in overactive bladder syndrome (OAB), and to examine the effects of connexin inhibitor on this condition. Adult female Wistar rats with OAB following partial bladder outlet obstruction (PBBO) (OAB group, n=37) and sham-operated rats (control group, n=17) were studied. The ultrastructure of the rat detrusor was observed by transmission electron microscopy and the protein expression levels of Cx43 were analyzed using western blot analysis. Furthermore, bladder detrusor cells in both groups were cultured and cells in the OAB group were randomly divided into ten groups. In nine of these groups, 18-ß glycyrrhetinic acid (18ß-GA) was administered at various doses and durations. All groups were compared using fluorescence redistribution after photobleaching and a laser scanning confocal microscope. Cystometry demonstrated that gap junctions were an abundant mechanism among adjacent cells, and Cx43 protein expression levels were increased in the OAB group following 6 weeks of obstruction, as compared with the control group. Mean fluorescence recovery rates in the OAB group were significantly increased, as compared with the control group (P<0.01). Mean fluorescence recovery rates were noted following 18ß-GA administration. These results suggested that upregulation of Cx43 induces structural and functional alterations in gap junctional intercellular communication following PBOO, and connexin inhibitors may be a novel therapeutic strategy for the clinical treatment of OAB.

12.
Medicine (Baltimore) ; 94(49): e2222, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26656362

RESUMO

The aim of the study is to evaluate the relationship between the adverse events and efficacy of sorafenib in patients with metastatic renal cell carcinoma (mRCC), with a purpose to guide the judgment of efficacy in sorafenib treatment.Eighty-three mRCC patients who received sorafenib therapy at northwest China were studied retrospectively. Univariate and multivariate analyses were performed to correlate tumor response, progression-free survival (PFS), and overall survival (OS) with adverse event types and grades.Among 83 patients who underwent sorafenib therapy, 2 cases (2.4%) had completed response (CR), 14 cases (16.9%) had partial response (PR), 57 cases (68.7%) had stable disease (SD), and 10 cases (12.0%) developed progressive disease (PD). The median PFS and OS were 15.0 and 29.0 months, respectively. The most frequent grade 1 or 2 adverse events included hand-foot syndrome (68.7%), diarrhea (54.2%), and alopecia (51.8%). The most common grade 3 or 4 adverse events were hand-foot syndrome (6.0%), hypertension (4.8%), and diarrhea (3.6%). The frequency and severity of adverse events correlated with tumor response rate (both with P < 0.05). Multivariate analysis showed the independent predictors of better PFS included rash (OR 0.307, 95%CI 0.148-0.636, P = 0.001) and diarrhea (OR 0.391, 95%CI 0.169-0.783, P = 0.008). Elevated transaminase was the independent predictor of poor PFS (OR 2.606, 95%CI 1.299-5.532, P = 0.012). For OS, rash (OR 0.473, 95%CI 0.253-0.886, P = 0.019) and diarrhea (OR 0.321, 95%CI 0.171-0.605, P = 0.000) correlated with better OS.Sorafenib-related adverse events are associated with efficacy in patients with mRCC from northwest China. Rash and diarrhea are independent protective factors of both PFS and OS, and elevated transaminase is an independent risk factor of PFS. A large prospective study is warranted.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , China , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Adulto Jovem
13.
Zhonghua Nan Ke Xue ; 21(5): 414-9, 2015 May.
Artigo em Chinês | MEDLINE | ID: mdl-26117938

RESUMO

OBJECTIVE: To study the relationship of the expression of FOXA1 in the prostate cancer (PCa) tissue with the Gleason score and clinical staging of PCa and with castration-resistant PCa (CRPC). METHODS: Using the immunohistochemical method, we detected the expressions of FOXA1 and Ki-67 in the pathological sections of 35 cases of PCa and 21 cases of benign prostatic hyperplasia (BPH). Then we analyzed their correlation with the Gleason score and TNM staging of PCa and that with CRPC. RESULTS: The positive expression of FOXA1 was significantly higher in the PCa than in the BPH tissue (P < 0.001) and was positively correlated with that of Ki-67 (P < 0.001) as well as with the Gleason score (P = 0.027) and clinical staging of PCa (P = 0.002), but showed no correlation with CRPC (P = 0.391). CONCLUSION: The positive expression of FOXA1 is increased in PCa, most significantly in the advanced stage of the tumor.


Assuntos
Fator 3-alfa Nuclear de Hepatócito/metabolismo , Antígeno Ki-67/metabolismo , Proteínas de Neoplasias/metabolismo , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Progressão da Doença , Humanos , Masculino , Gradação de Tumores , Hiperplasia Prostática/patologia
14.
Asian Pac J Cancer Prev ; 16(5): 1977-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25773797

RESUMO

OBJECTIVE: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. MATERIALS AND METHODS: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. RESULTS: Three novel mutations (H125P, 623(?TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding ß-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(?TTTGTtG) carriers presented VHL type 2B or type 2C. CONCLUSIONS: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(?TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research into VHLD pathogenesis.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Povo Asiático/genética , Proteínas de Transporte/genética , Predisposição Genética para Doença/genética , Mutação/genética , Feocromocitoma/genética , Adolescente , Adulto , Criança , Proteínas do Citoesqueleto , Análise Mutacional de DNA/métodos , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares , Linhagem , Adulto Jovem , Doença de von Hippel-Lindau/genética
15.
Zhonghua Nan Ke Xue ; 20(3): 277-80, 2014 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-24738469

RESUMO

The role of autophagy is known to be highly complex and context-dependent, and may be characterized as both tumor suppression and tumor promotion in some tumors, such as breast cancer and prostate cancer. This review outlines recent advances in the studies of the involvement of autophagy in the development, progression and treatment of prostate cancer, focusing on autophagy modulation during androgen deprivation, with a special discussion on the regulatory effect of androgens on the autophagy of prostate cancer cells. A critical evaluation and analysis of the studies suggests that autophagy inhibition combined with androgen deprivation therapy is a promising approach to the treatment of prostate cancer.


Assuntos
Autofagia , Neoplasias da Próstata , Humanos , Masculino
16.
Zhonghua Nan Ke Xue ; 19(4): 315-20, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23678709

RESUMO

OBJECTIVE: To explore the expressions of SIgA and alpha l-AR in benign prostatic hyperplasia (BPH) complicated by chronic prostatitis (CP) and their implications. METHODS: According to the preoperative findings of expressed prostatic secretion (EPS), transrectal prostate ultrasonography, prostate-specific antigen (PSA), international prostate symptom score (IPSS), clinical symptoms, chronic pelvic pain syndrome (CPPS) and postoperative histopathology, 62 cases of BPH pathologically confirmed after transurethral plasma kinetic resection of the prostate (PKRP) were divided into a BPH group (n = 32) and a BPH + CP group (n = 30). The expressions of SIgA and alpha 1-AR in the prostate tissue were determined by immunohistochemistry and PT-PCR. RESULTS: Of the 62 cases, 30 were found to be BPH + CP, and the other 32 to be BPH. The expressions of SIgA and alpha1-AR were significantly higher in the BPH + CP than in the BPH group (0.380 8 +/- 0.144 3 vs 0.295 4 +/- 0.008 4 and 0.440 5 +/- 0.104 1 vs 0.383 2 +/- 0.013 6, P < 0.05). CONCLUSION: The upregulated expressions of SIgA and alpha1-AR expression in BPH complicated by CP suggest a certain association between CP and BPH, and that inflammation may be a pathogenic factor of BPH and correlate with its pathological development.


Assuntos
Imunoglobulina A Secretora/metabolismo , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Prostatite/metabolismo , Receptores Androgênicos/metabolismo , Idoso , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/patologia , Prostatite/complicações , Prostatite/patologia
17.
Zhonghua Nan Ke Xue ; 19(9): 826-30, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24386863

RESUMO

Recent studies have demonstrated the importance of the non-protein coding part of human genome in carcinogenesis and metastasis of prostate cancer. Long non-coding RNAs (lncRNAs) play a key regulatory role in prostate cancer biology. LncRNAs are dysregulated in prostate cancer and the expression levels of certain lncRNAs are associated with the recurrence, metastasis and prognosis of cancer. It is also proved that lncRNAs, as oncogenes, can promote carcinogenesis and development of prostate cancer. This review focuses on the progress in the studies of lncRNAs in prostate cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Próstata/genética , RNA Longo não Codificante , Humanos , Masculino
18.
Zhonghua Nan Ke Xue ; 18(9): 835-9, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-23193675

RESUMO

Recent studies show that long exposure to high altitude and hypoxia can seriously affect men's reproductive health by reducing their sperm concentration, which decreases with the increase of altitude. High altitude and hypoxia are strongly associated with spermatogenic reduction, sperm DNA damage, sperm apoptosis, and decreased level of sex hormones. This article reviews the mechanisms of high altitude and hypoxia affecting sperm concentration.


Assuntos
Altitude , Hipóxia , Espermatozoides/fisiologia , Humanos , Masculino , Contagem de Espermatozoides , Espermatogênese
19.
Urology ; 78(5): 1142-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22054390

RESUMO

OBJECTIVES: To compare the prevalence, symptoms, and pathologic changes related to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with significant prostatitis-like symptoms between 2 altitude areas in northwest China. METHODS: From October 2009 to March 2010 community male residents at 3000 m (Delingha) and 400 m (Xi'An) constituted the population base for the present cross-sectional study. All participants completed a detailed questionnaire containing the National Institutes of Health Chronic Prostatitis Symptom Index, and the subjects who met our definition were invited to undergo clinical evaluation. After screening, the subjects considered to have CP/CPPS were separated into 2 groups: those with type IIIa and those with type IIIb CP/CPPS. RESULTS: The prevalence of CP/CPPS with significant prostatitis-like symptoms was significantly different between the 2 groups. Moreover, the National Institutes of Health Chronic Prostatitis Symptom Index of patients with type IIIa and IIIb in 2 groups differed significantly, indicating the aggravation of symptoms of CP/CPPS at a high altitude. Additional investigations showed that reactive oxygen species were increased, accompanied by a decrease in the total antioxidant capacity in the expressed prostatic secretions of patients with type IIIa at a higher altitude. In addition, the tumor necrosis factor-α, interleukin-8, and interleukin-10 levels in the expressed prostatic secretions of patients with type IIIa in Delingha were increased compared with that in the patients with type IIIa in Xi'An. Notably, the interleukin-6 level in the expressed prostatic secretions was greater in those with type IIIa and IIIb at a higher altitude than in those with type IIIa and IIIb at a low altitude. CONCLUSIONS: At a high altitude, the symptoms of CP/CPPS were aggravated. Oxidative stress and cytokines might involve in the pathologic process and the aggravation of symptoms. In addition, in a high altitude area the pathomechanisms of type IIIa and IIIb CP/CPPS differed.


Assuntos
Prostatite/diagnóstico , Prostatite/epidemiologia , Adulto , Altitude , China/epidemiologia , Meio Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
20.
Zhonghua Nan Ke Xue ; 17(4): 310-3, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21548206

RESUMO

OBJECTIVE: To investigate the therapeutic effect of pentosan polysulfide sodium (PPS) on chronic non-bacterial prostatitis (CNP) in rats. METHODS: Based on Robinette's method, we established a CNP model in 80 male SD rats, aged 6 months and weighing 315 - 450 g, by castration followed by subcutaneous injection of estradiol at 0.25 mg / (kg x d) for 30 consecutive days. Then we randomly allocated the model rats into a placebo group (n = 40) and a PPS group (n = 40) to receive intragastric administration of normal saline and PPS, respectively. After 8 weeks of treatment, the pathological changes in the rat prostatic tissue were observed by HE staining. RESULTS: Varied degrees of chronic inflammation and inflammatory cell infiltration were seen in the prostatic tissues of both groups of rats before the treatment. The inflammation was significantly improved after the treatment in the PPS group but not in the placebo group. CONCLUSION: PPS has some therapeutic effect on CNP in the rat, and its mechanism may be associated with the abilities of PPS to repair the damaged glycosaminoglycan layer and inhibit inflammation in the prostate.


Assuntos
Poliéster Sulfúrico de Pentosana/uso terapêutico , Prostatite/tratamento farmacológico , Animais , Doença Crônica , Cistite Intersticial/tratamento farmacológico , Modelos Animais de Doenças , Masculino , Próstata/patologia , Prostatite/patologia , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...