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1.
J Surg Oncol ; 129(6): 1073-1081, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38321865

RESUMEN

OBJECTIVE: To investigate the effect of adrenal surgery on blood pressure (BP) improvements in patients with hormone-negative adrenal adenoma (HNA) concomitant with hypertension and analyze associated prognostic factors. METHODS: We retrospectively reviewed the clinical data of patients with HNA and hypertension and patients with aldosterone-producing adenoma (APA) and hypertension who underwent adrenal surgery at our center between 2019 and 2022. Hypertension outcomes were evaluated in all patients and subjects were divided into three groups according to follow-up BP and the administration of anti-hypertensive agents: a clinical curation group, an improvement group, and a no-improvement group. Logistic regression analysis was performed to predict factors associated with clinical curation in patients with HNA post-surgery. RESULTS: Of the 182 patients with HNA, clinical curation was achieved in 58 patients (31.9%), improvement in 72 (39.5%), and no improvement in 52 (28.6%). The clinical curation, improvement and no improvement rates in patients with APA were 64.8% (n = 118), 15.9% (n = 29), and 19.2% (n = 35). Multivariate logistic regression analysis indicated that a duration of hypertension ≤6 years and a plasma aldosterone level >160 pg/ml were both independent factors for the clinical curation of hypertension in patients with HNA after adrenal surgery. CONCLUSION: Adrenal surgery can cure or improve hypertension in most patients with HNA, especially in a short duration of hypertension and high plasma levels of aldosterone.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Adrenalectomía , Presión Sanguínea , Hipertensión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias de las Glándulas Suprarrenales/metabolismo , Adenoma/cirugía , Adenoma/metabolismo , Adenoma/complicaciones , Adenoma/patología , Pronóstico , Adulto , Estudios de Seguimiento , Aldosterona/sangre , Adenoma Corticosuprarrenal/cirugía , Adenoma Corticosuprarrenal/complicaciones , Adenoma Corticosuprarrenal/metabolismo , Anciano
2.
Gynecol Endocrinol ; 37(1): 97-100, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32945709

RESUMEN

Mutations of the CYP17A1 gene could cause complete or partial and combined or isolated 17α-hydroxylase/17,20-lyase deficiency (17OHD), which is characterized by hypertension, hypokalemia, and abnormal development of the genitalia. Most of the mutations are located in the coding sequence, and very few are located in the intronic region. The aim of this study is to investigate the novel intronic CYP17A1 mutation and its possible influence on phenotype. A 30-year-old Chinese female patient (46, XY) was referred to our Urology Department for severe hypertension, hypokalemia and a right adrenal mass. Physical examination revealed a hypertrophic clitoris and blind-ending vagina. Hormone analysis exhibited increased concentrations of ACTH and low levels of cortisol and sexual steroids. Mutation analysis revealed compound heterozygous CYP17A1 mutations, with c.1072C > T (p.Arg358*) in one allele and a novel intronic splicing mutation (c.970-1G > A) in another allele. Bioinformatics software predicted that the novel mutation may activate a cryptic splice site, shifting the reading frame and introducing a premature stop codon. In conclusion, we discovered a novel splicing mutation of the CYP17A1 gene in a Chinese patient with 17OHD. Our study extended the CYP17A1 mutation spectrum and provided valuable information for patient management and genetic counseling.


Asunto(s)
Hiperplasia Suprarrenal Congénita/genética , Sistema Enzimático del Citocromo P-450/deficiencia , Sitios de Empalme de ARN/genética , Esteroide 17-alfa-Hidroxilasa/genética , Adulto , Codón sin Sentido , Sistema Enzimático del Citocromo P-450/genética , Femenino , Humanos , Intrones
3.
Zhonghua Nan Ke Xue ; 27(8): 733-737, 2021 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34914247

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of Lingze Tablets in the treatment of BPH with kidney deficiency, blood stasis and dampness resistance. METHODS: Totally 235 eligible BPH patients, aged 50-80 years and meeting the inclusion criteria, were enrolled and treated with Lingze Tablets orally, 4 tablets per time, tid. Before and after an 8-week course of medication, IPSS, quality of life (QOL) and TCM syndromes scores were obtained from the patients. RESULTS: Of the total number of patients, 211 completed the whole course of treatment. Compared with the baseline, the IPSS was dramatically reduced after 4 and 8 weeks of medication (18.28 ± 5.29 vs 12.82 ± 4.66 and 9.23 ± 4.21, P < 0.01), and so were the QOL scores (6.44 ± 1.99 vs 4.95 ± 1.64 and 3.16 ± 1.53, P < 0.01) and TCM syndromes scores (17.49 ± 5.30 vs 12.45 ± 3.74 and 9.17 ± 3.24, P < 0.01). The incidence rates of adverse events and drug-related adverse reactions were 15.2% and 1.9%, respectively, and no organ function impairment was observed. CONCLUSIONS: Lingze Tablets are definitely effective and safe for the treatment of BPH with kidney deficiency, blood stasis and dampness resistance.


Asunto(s)
Hiperplasia Prostática , Calidad de Vida , Humanos , Riñón , Comprimidos
4.
J Cell Mol Med ; 24(24): 14441-14452, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33145941

RESUMEN

The microphthalmia of bHLH-LZ transcription factor (MiT/TFE) family chromosomal translocation or overexpression is linked with a poor prognosis in clear cell renal cell carcinoma (ccRCC) with elevated recurrence and drug resistance, but the molecular mechanism is not fully understood. Here, we investigated whether the resistance to sunitinib (Sun), the standard treatment for metastatic ccRCC, is due to up-regulation of programmed death ligand 1 (PD-L1) by the transcription factor E3 (TFE3). In this study, we propose that TFE3 but not TFEB is essential for tumour survival which was associated with the poorer survival of cancer patients. We also found a positive correlation between TFE3 and PD-L1 expression in ccRCC cells and tissues. Sun treatment led to enhanced TFE3 nuclear translocation and PD-L1 expression. Finally, we observed the therapeutic benefit of Sun plus PD-L1 inhibition which enhanced CD8+ cytolytic activity and thus tumour suppression in a xenografted mouse model. These data revealed that TFE3 is a potent tumour promoting gene and it mediates resistance to Sun by induction of PD-L1 in ccRCC. Our data provide a strong rationale to apply Sun and PD-L1 inhibition jointly as a novel immunotherapeutic approach for ccRCC treatment.


Asunto(s)
Antígeno B7-H1/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Carcinoma de Células Renales/metabolismo , Resistencia a Antineoplásicos , Neoplasias Renales/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Sunitinib/farmacología , Animales , Antígeno B7-H1/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/agonistas , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/etiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/etiología , Terapia Molecular Dirigida , Escape del Tumor/genética , Ensayos Antitumor por Modelo de Xenoinjerto
5.
Zhonghua Nan Ke Xue ; 24(9): 819-823, 2018 Sep.
Artículo en Zh | MEDLINE | ID: mdl-32212461

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of Huang'e Capsules in the treatment of BPH with Qi-deficiency, blood stasis and damp heat block. METHODS: This study included 1 456 cases of BPH with Qi-deficiency, blood stasis and damp heat block from 40 hospitals of Zhejiang and Anhui Provinces between June 2014 and July 2017. The patients were aged 40-85 years and treated with Huang'e Capsules at a dose of 4 capsules, tid, for a course of 6 weeks. The IPSSs of the patients were obtained before and after 2, 4 and 6 weeks of medication, and a stratified analysis was made on the factors influencing the therapeutic effects, such as age, the stage of BPH, and concomitant medication of urogenital and reproductive hormone drugs. RESULTS: After 6 weeks of medication, the IPSS of the patients was decreased by 8.4 ± 5.4 (ï¼»42.9 ± 22.7ï¼½ %) as compared with the baseline (19.2 ± 6.8) (P < 0.05), with a total effectiveness rate of 71.9% and an excellence rate of 23.1%. After 6 weeks of medication, the IPSSs of the patients with stage-Ⅰ, -Ⅱ and -Ⅲ BPH were decreased by 7.3 ± 6.8, 6.6 ± 4.3 and 11.0 ± 5.5, with total effective rates of 69.5%, 70.1% and 74.7%, respectively, with statistically significant differences among the three stages (P < 0.05), and so were those in the patients aged ≤50 years (by 7.4 ± 5.8), 51-60 years (by 7.9 ± 5.3), 61-70 years (by 8.7 ± 5.6) and >70 years (by 8.6 ± 5.1), but with no statistically significant differences among different age groups (P > 0.05). At 6 weeks, the IPSS was reduced by 7.1 ± 5.9 by concomitant medication of urogenital and reproductive hormone drugs, 8.7 ± 5.4 by concomitant medication of other drugs, and 8.4 ± 5.3 by non-concomitant medication, with no statistically significant differences among the three types of medication (P > 0.05). CONCLUSIONS: Huang'e Capsules can evidently improve the symptoms of BPH, with the best effect on stage-Ⅲ BPH, and the effect does not differ significantly with age or drug concomitance.

6.
Zhonghua Nan Ke Xue ; 20(9): 824-9, 2014 Sep.
Artículo en Zh | MEDLINE | ID: mdl-25306812

RESUMEN

OBJECTIVE: To investigate the effects of Bushen Huoxue Fang (BSHX) on the apoptosis of epithelial cells in the prostatic ductal system of rats with benign prostatic hyperplasia (BPH) and its possible action mechanism. METHODS: One hundred 3- month-old male Wistar rats were randomly divided into four groups of equal number (control, castrated, BPH model, and BSHX). BPH models were made by subcutaneous injection of testosterone following castration; the rats in the BSHX group were treated intragastrically with BSHX at 2.34 g/ml after modeling, while those in the other two groups with equal volume of saline, all for 37 days. On the 38th day, all the rats were sacrificed and their prostates harvested for detection of the distribution of TGF-beta1 and alpha-actin and the count of positive cells in the prostatic ductal system by immunohistochemical staining. The apoptosis rate of epithelial cells in the prostatic ductal system was determined by TUNEL assay. RESULTS: The expression of TGF-beta1 was significantly increased in the rats of the BSHX group as compared with the BPH models in both the proximal prostatic duct ([15.28 +/- 4.30]% vs [36.42 +/- 8.10]%, P < 0.01) and the distal prostatic duct ([4.42 +/- 2.07]% vs [8.71 +/- 2.28 ]%, P < 0.05), while the expression of alpha-actin in the proximal duct was remarkably higher in the BSHX-treated rats than in the models ([28.14 +/- 7.43]% vs [18.28 +/- 4.07]%, P < 0.01), but lower than in the control animals ([33.57 +/- 6.85]%, P < 0.05). Compared with the control group, the BPH models and BSHX-treated rats both exhibited markedly decreased apoptosis of epithelial cells in the proximal prostatic duct ([39.42 +/- 9.20]% vs [3.86 +/- 1.34]%, P < 0.01, and [31.14 +/- 5.64]%, P < 0.01) and distal prostatic duct ([17.60 +/- 4.86]% vs [3.07 +/- 1.14]%, P < 0.01, and [12.37 +/- 2.25]%, P < 0.05). The apoptosis rate of epithelial cells in the prostatic ductal system was significantly higher in the BSHX-treated rats than in the BPH models (P < 0.01). CONCLUSION: By upregulating the expression of TGF-beta, BSHX can suppress the reduction of smooth muscle cells in the proximal prostatic duct, promote the apoptosis of prostatic epithelial cells, and thus effectively inhibit benign prostatic hyperplasia.


Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Células Epiteliales/efectos de los fármacos , Hiperplasia Prostática/patología , Factor de Crecimiento Transformador beta1/metabolismo , Actinas/metabolismo , Animales , Modelos Animales de Enfermedad , Células Epiteliales/patología , Masculino , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/metabolismo , Ratas , Ratas Wistar
7.
J Surg Case Rep ; 2024(3): rjae100, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38455983

RESUMEN

Teratoma are germ cell tumors, most frequently arising in the gonads and retroperitoneal teratomas are rare, especially adrenal teratomas. Only a few case reports have been documented in the literature so far. We report the case of a 52-year-old asymptomatic male patient who had an incidental finding of a left adrenal teratoma during an abdominal computed tomography scan; due to the large size of the tumor, he underwent laparoscopic left adrenalectomy, and histopathological examination revealed a mature teratoma of the left adrenal gland, Patient recovering well after surgery and had no recurrence after 6 months of postoperative follow-up. The preoperative diagnosis of adrenal teratoma is challenging because imaging features are usually non-specific. Minimally invasive surgical resection is the best option for diagnosis and treatment of adrenal teratoma.

8.
Int J Surg Case Rep ; 116: 109341, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38340623

RESUMEN

INTRODUCTION: The occurrence of hypercortisolism resulting from adrenocorticotropic hormone (ACTH)-secreting pheochromocytoma is exceedingly uncommon, with limited documented instances thus far. PRESENTATION OF CASE: We present a case of ectopic ACTH-secreting pheochromocytoma in a patient who suffered from severe metabolic disorders. Our clinical case outlines the diagnostic history, preoperative correction of the patient's metabolic disturbances and surgical strategy for management of a rare ectopic ACTH producing pheochromocytoma. DISCUSSION: Ectopic adrenocorticotropic hormone-secreting pheochromocytoma displays multifaceted clinical features and requires prompt diagnosis and multidisciplinary management in order to overcome the related severe clinical derangements. CONCLUSION: The combination of biochemical and hormonal testing and imaging procedures is mandatory for the diagnosis of ectopic ACTH secretion, and in the presence of an adrenal mass, the possibility of an ACTH-secreting pheochromocytoma should be taken into account.

9.
PLoS Pathog ; 7(10): e1002285, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21998584

RESUMEN

The molecular details of Chlamydia trachomatis binding, entry, and spread are incompletely understood, but heparan sulfate proteoglycans (HSPGs) play a role in the initial binding steps. As cell surface HSPGs facilitate the interactions of many growth factors with their receptors, we investigated the role of HSPG-dependent growth factors in C. trachomatis infection. Here, we report a novel finding that Fibroblast Growth Factor 2 (FGF2) is necessary and sufficient to enhance C. trachomatis binding to host cells in an HSPG-dependent manner. FGF2 binds directly to elementary bodies (EBs) where it may function as a bridging molecule to facilitate interactions of EBs with the FGF receptor (FGFR) on the cell surface. Upon EB binding, FGFR is activated locally and contributes to bacterial uptake into non-phagocytic cells. We further show that C. trachomatis infection stimulates fgf2 transcription and enhances production and release of FGF2 through a pathway that requires bacterial protein synthesis and activation of the Erk1/2 signaling pathway but that is independent of FGFR activation. Intracellular replication of the bacteria results in host proteosome-mediated degradation of the high molecular weight (HMW) isoforms of FGF2 and increased amounts of the low molecular weight (LMW) isoforms, which are released upon host cell death. Finally, we demonstrate the in vivo relevance of these findings by showing that conditioned medium from C. trachomatis infected cells is enriched for LMW FGF2, accounting for its ability to enhance C. trachomatis infectivity in additional rounds of infection. Together, these results demonstrate that C. trachomatis utilizes multiple mechanisms to co-opt the host cell FGF2 pathway to enhance bacterial infection and spread.


Asunto(s)
Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/patogenicidad , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Caspasa 1/metabolismo , Infecciones por Chlamydia/metabolismo , Chlamydia trachomatis/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Células HeLa , Proteoglicanos de Heparán Sulfato/metabolismo , Humanos , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Unión Proteica , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo , Transcripción Genética , Regulación hacia Arriba , Vacuolas/metabolismo
10.
PLoS Pathog ; 7(9): e1002198, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21909260

RESUMEN

The strain designated Chlamydia trachomatis serovar that was used for experiments in this paper is Chlamydia muridarum, a species closely related to C. trachomatis (and formerly termed the Mouse Pneumonitis strain of C. trachomatis. [corrected]. The obligate intracellular pathogen Chlamydia trachomatis replicates within a membrane-bound inclusion that acquires host sphingomyelin (SM), a process that is essential for replication as well as inclusion biogenesis. Previous studies demonstrate that SM is acquired by a Brefeldin A (BFA)-sensitive vesicular trafficking pathway, although paradoxically, this pathway is dispensable for bacterial replication. This finding suggests that other lipid transport mechanisms are involved in the acquisition of host SM. In this work, we interrogated the role of specific components of BFA-sensitive and BFA-insensitive lipid trafficking pathways to define their contribution in SM acquisition during infection. We found that C. trachomatis hijacks components of both vesicular and non-vesicular lipid trafficking pathways for SM acquisition but that the SM obtained from these separate pathways is being utilized by the pathogen in different ways. We show that C. trachomatis selectively co-opts only one of the three known BFA targets, GBF1, a regulator of Arf1-dependent vesicular trafficking within the early secretory pathway for vesicle-mediated SM acquisition. The Arf1/GBF1-dependent pathway of SM acquisition is essential for inclusion membrane growth and stability but is not required for bacterial replication. In contrast, we show that C. trachomatis co-opts CERT, a lipid transfer protein that is a key component in non-vesicular ER to trans-Golgi trafficking of ceramide (the precursor for SM), for C. trachomatis replication. We demonstrate that C. trachomatis recruits CERT, its ER binding partner, VAP-A, and SM synthases, SMS1 and SMS2, to the inclusion and propose that these proteins establish an on-site SM biosynthetic factory at or near the inclusion. We hypothesize that SM acquired by CERT-dependent transport of ceramide and subsequent conversion to SM is necessary for C. trachomatis replication whereas SM acquired by the GBF1-dependent pathway is essential for inclusion growth and stability. Our results reveal a novel mechanism by which an intracellular pathogen redirects SM biosynthesis to its replicative niche.


Asunto(s)
Chlamydia trachomatis/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Cuerpos de Inclusión/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Esfingomielinas/biosíntesis , Proteínas de Transporte Vesicular/metabolismo , Amidas/farmacología , Benzamidas/farmacología , Benzoatos/farmacología , Brefeldino A/farmacología , Quinasa de la Caseína I/metabolismo , Chlamydia trachomatis/crecimiento & desarrollo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Células HeLa , Humanos , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Transferasas (Grupos de Otros Fosfatos Sustitutos)/metabolismo
11.
J Transl Int Med ; 11(3): 275-281, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37662893

RESUMEN

Background and Objectives: Treatment resistant hypertension (trHTN) is a common clinical problem faced by many clinicians. Laparoscopic adrenalectomy effectively trims blood pressure (BP) elevation secondary to various functional adrenal disorders. However, the impact of adrenalectomy on BP within trHTN patients has never been reported. Our present study aims to investigate the effect of adrenalectomy on BP management within trHTN patients, and to explore clinical predictors for postoperative BP normalization. Patients and Methods: In our current study, 117 patients diagnosed with trHTN and performed with unilateral adrenalectomy were consecutively enrolled, demographic and medical information were documented for baseline data collection. BP was measured with a standard electronic sphygmomanometer twice a day. Long-term periodical interview was conducted and 109 (93.2%) enrolled patients were successfully followed-up at an averaged 36.2 months. Results: At follow-up, 27/109 (25%) trHTN patients acquired BP normalization and 68/109 (62%) patients acquired BP improvement. Mean taking anti-hypertensive agents reduced from presurgical 4.24 to present 1.21 (P < 0.01), along with 7.2 mmHg reduction in SBP (P < 0.01). Image macro-adenoma and hypokalemia history were found to be the two strongest predictors for postoperative BP normalization. (χ2= 28.032, P < 0.01). The incidence of adverse postoperative events was quite small. Conclusions: In summary, this current study implicates that adrenalectomy is an efficacious and safe surgical strategy for BP management in trHTN patients. Patients with both unilateral macro-adenoma and hypokalemia are more prone to acquire postoperative BP normalization.

12.
Front Immunol ; 14: 1097472, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36761744

RESUMEN

Background: Bladder urothelial carcinoma (BLCA) is associated with high mortality and recurrence. Although mRNA-based vaccines are promising treatment strategies for combating multiple solid cancers, their efficacy against BLCA remains unclear. We aimed to identify potential effective antigens of BLCA for the development of mRNA-based vaccines and screen for immune clusters to select appropriate candidates for vaccination. Methods: Gene expression microarray data and clinical information were retrieved from The Cancer Genome Atlas and GSE32894, respectively. The mRNA splicing patterns were obtained from the SpliceSeq portal. The cBioPortal for Cancer Genomics was used to visualize genetic alteration profiles. Furthermore, nonsense-mediated mRNA decay (NMD) analysis, correlation analysis, consensus clustering analysis, immune cell infiltration analysis, and weighted co-expression network analysis were conducted. Results: Six upregulated and mutated tumor antigens related to NMD, and infiltration of APCs were identified in patients with BLCA, including HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2. The patients were subdivided into two immune clusters (IC1 and IC2) with distinct clinical, cellular and molecular features. Patients in IC1 represented immunologically 'hot' phenotypes, whereas those in IC2 represented immunologically 'cold' phenotypes. Moreover, the survival rate was better in IC2 than in IC1, and the immune landscape of BLCA indicated significant inter-patient heterogeneity. Finally, CALD1, TGFB3, and ANXA6 were identified as key genes of BLCA through WGCNA analysis, and their mRNA expression levels were measured using qRT-PCR. Conclusion: HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2 were identified as potential antigens for developing mRNA-based vaccines against BLCA, and patients in IC2 might benefit more from vaccination.


Asunto(s)
Vacunas contra el Cáncer , Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Vacunas de ARNm , Humanos , Antígenos de Neoplasias/genética , Carcinoma de Células Transicionales/genética , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Vacunas contra el Cáncer/genética
13.
Arch Med Sci ; 18(1): 183-194, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35154539

RESUMEN

INTRODUCTION: Emerging evidence has illustrated that Collagen triple helix repeat containing 1 (CTHRC1) is crucial for tumorigenesis and development. However, the effects of CTHRC1 on bladder cancer progression remain largely unclear. Here, we aim to investigate the function and mechanism of CTHRC1 in behaviors of bladder cancer cells in vitro and in vivo. MATERIAL AND METHODS: Interference assays were applied to determine the biological functions of CTHRC1. The expression of CTHRC1 was examined by quantitative real time-PCR (qRT-PCR), Western blot and immunohistochemical (IHC) analysis. Effects of CTHRC1 on proliferation, migration and invasion were evaluated by CCK-8, colony formation, flow cytometry, EdU staining, wound healing, transwell and western blot assays. Bladder cancer cells transfected with sh-CTHRC1 were injected into nude mice to explore the effect of CTHRC1 on tumorigenesis in vivo. RESULTS: CTHRC1 expression was increased in bladder cancer tissues and cell lines compared with normal controls, and associated with advanced clinical stage and lymph node metastasis. Also, patients with high levels of CTHRC1 expression were found to have a poor prognosis. Knockdown of CTHRC1 alleviated bladder cancer cell proliferation, migration and invasion in vitro and impeded tumorigenesis in vivo. Moreover, mechanistic investigation indicated that CTHRC1 could regulate the PI3K/Akt signaling pathway. CONCLUSIONS: Our data demonstrated that CTHRC1 played an oncogenic role in bladder cancer by modulating the PI3K/Akt signaling pathway, which sheds novel light on diagnosis and treatment of bladder cancer.

14.
Front Immunol ; 13: 818984, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35250999

RESUMEN

Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent primary malignancies with high heterogeneity in the urological system. Growing evidence implies that lactate is a significant carbon source for cell metabolism and plays a vital role in tumor development, maintenance, and therapeutic response. However, the global influence of lactate-related genes (LRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response has not been comprehensively elucidated in patients with KIRC. In the present study, we collected RNA sequencing and clinical data of KIRC from The Cancer Genome Atlas (TCGA), E-MTAB-1980, and GSE22541 cohorts. Unsupervised clustering of 17 differentially expressed LRG profiles divided the samples into three clusters with distinct immune characteristics. Three genes (FBP1, HADH, and TYMP) were then identified to construct a lactate-related prognostic signature (LRPS) using the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses. The novel signature exhibited excellent robustness and predictive ability for the overall survival of patients. In addition, the constructed nomogram based on the LRPS-based risk scores and clinical factors (age, gender, tumor grade, and stage) showed a robust predictive performance. Furthermore, patients classified by risk scores had distinguishable immune status, tumor mutation burden, response to immunotherapy, and sensitivity to drugs. In conclusion, we developed an LRPS for KIRC that was closely related to the immune landscape and therapeutic response. This LRPS may guide clinicians to make more precise and personalized treatment decisions for KIRC patients.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/patología , Femenino , Humanos , Inmunidad , Riñón/patología , Neoplasias Renales/patología , Ácido Láctico , Masculino , Pronóstico , Microambiente Tumoral/genética
15.
Aging (Albany NY) ; 13(6): 8276-8289, 2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33686951

RESUMEN

Metabolic reprogramming contributes to the high mortality of advanced stage kidney renal clear cell carcinoma (KIRC), the most common renal cancer subtype. This study aimed to identify a metabolism-related gene (MRG) signature to improve survival prediction in KIRC patients. We downloaded RNA sequencing data and corresponding clinical information for KIRC and control samples from The Cancer Genome Atlas database and identified, based on an MRG dataset in the Molecular Signatures Database, 123 MRGs with differential expression in KIRC. Following Cox regression analysis and least absolute shrinkage and selection operator selection, RRM2 and ALDH6A1 were identified as prognosis-related genes and used to construct a prognostic signature with independent prognostic significance. After risk score-based patient separation, stratified survival analysis indicated that high-risk patients showed poorer overall survival than low-risk patients. We then constructed a clinical nomogram that showed a concordance index of 0.774 and good performance based upon calibration curves. Gene set enrichment analysis revealed several metabolic pathways significantly enriched in the target genes. The two-gene metabolic signature identified herein may represent a highly valuable tool for KIRC prognosis prediction, and might also help identify new metabolism-related biomarkers and therapeutic targets for KIRC.


Asunto(s)
Aldehído Oxidorreductasas/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Ribonucleósido Difosfato Reductasa/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Nomogramas , Pronóstico , Transcriptoma
16.
Ther Adv Urol ; 13: 1756287220984046, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33633798

RESUMEN

AIMS: Management of inflammatory renal disease (IRD) can still be technically challenging for laparoscopic procedures. The aim of the present study was to compare the safety and feasibility of laparoscopic and hand-assisted laparoscopic nephrectomy in patients with IRD. PATIENTS AND METHODS: We retrospectively analyzed the data of 107 patients who underwent laparoscopic nephrectomy (LN) and hand-assisted laparoscopic nephrectomy (HALN) for IRD from January 2008 to March 2020, including pyonephrosis, renal tuberculosis, hydronephrosis, and xanthogranulomatous pyelonephritis. Patient demographics, operative outcomes, and postoperative recovery and complications were compared between the LN and HALN groups. Multivariable logistic regression analysis was conducted to identify the independent predictors of adverse outcomes. RESULTS: Fifty-five subjects in the LN group and 52 subjects in the HALN group were enrolled in this study. In the LN group, laparoscopic nephrectomy was successfully performed in 50 patients (90.9%), while four (7.3%) patients were converted to HALN and one (1.8%) case was converted to open procedure. In HALN group, operations were completed in 51 (98.1%) patients and conversion to open surgery was necessary in one patient (1.9%). The LN group had a shorter median incision length (5 cm versus 7 cm, p < 0.01) but a longer median operative duration (140 min versus 105 min, p < 0.01) than the HALN group. There was no significant difference in blood loss, intraoperative complication rate, postoperative complication rate, recovery of bowel function, and hospital stay between the two groups. Multivariable logistic regression revealed that severe perinephric adhesions was an independent predictor of adverse outcomes. CONCLUSION: Both LN and HALN appear to be safe and feasible for IRD. As a still minimally invasive approach, HALN provided an alternative to IRD or when conversion was needed in LN.

17.
Front Oncol ; 11: 716854, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34568046

RESUMEN

Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.

18.
Front Med (Lausanne) ; 8: 785331, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34881275

RESUMEN

Background: Tripartite motif containing 46 was initially identified as the oncogene in several human tumors. However, the clinical value and potential functions of tripartite motif containing 46 (TRIM46) in clear cell renal cell carcinoma (ccRCC) remained largely unclear. Methods: The expressing patterns, clinical involvement, and prognostic values of TRIM46 were analyzed using the data obtained from TCGA and GEO databases. A nomogram was constructed to examine the outcome of patients with ccRCC. We estimated the association between TRIM46 with tumor immunity in ccRCC. Results: Tripartite motif containing 46 was highly expressed in ccRCC, and its upregulation revealed an unfavorable prognosis. A nomogram based on TRIM46 expressions and other independent prognostic factors could robustly predict the overall survival of tumor patients. TRIM46 has a strong positive correlation with NUMBL, CACNB1, THBS3, ROBO3, MAP3K12, ANKRD13D, PIF1, PRELID3A, ANKRD13B, and PCNX2. Mechanically, TRIM46 displayed regulatory functions in ccRCC progression via several tumor-associated pathways. Besides, we observed that TRIM46 was distinctly related to tumor immunity in ccRCC. Conclusions: Our findings provide a novel tumor promotive role regarding TRIM46 function in the malignant progression of ccRCC.

19.
J Int Med Res ; 48(10): 300060520961238, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33044120

RESUMEN

OBJECTIVE: To compare the operative and oncologic outcomes between hand-assisted laparoscopic radical nephrectomy (HALRN) and laparoscopic radical nephrectomy (LRN) for large (stage ≥T2b) and locally advanced renal cell carcinoma. METHODS: We retrospectively collected data from patients who underwent HALRN or LRN for stage ≥T2b renal cell carcinoma from January 2011 to January 2018 in our institution. The patients' demographics, perioperative parameters, and postoperative follow-up data were compared between the two groups. The survival outcome was estimated using the Kaplan-Meier method. RESULTS: The HALRN group comprised 78 patients, and the LRN group comprised 63 patients. The median operative duration was significantly shorter in the HALRN than LRN group. The two groups were equivalent in terms of the incision length, blood loss, complication rate, and duration of hospitalization. In the HALRN and LRN groups, the 5-year overall survival rates were 69.4% and 73.1%, the 5-year cancer-specific survival rates were 80.0% and 83.3%, and the 5-year progression-free survival rates were 66.4% and 74.7%, respectively, with no significant differences. CONCLUSIONS: Compared with LRN, HALRN may offer a shorter operative duration and equivalent surgical outcomes without sacrificing oncological efficacy. In addition, HALRN has specific advantages for extremely large and complicated renal tumors.


Asunto(s)
Carcinoma de Células Renales , Laparoscópía Mano-Asistida , Neoplasias Renales , Laparoscopía , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/cirugía , Nefrectomía , Estudios Retrospectivos , Resultado del Tratamiento
20.
Medicine (Baltimore) ; 98(52): e18422, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31876718

RESUMEN

RATIONALE: Extramedullary plasmacytoma (EMP) is a very rare malignant neoplasm arising from clonal proliferation of atypical plasma cells. Most EMPs involve mucosal lymphoid tissue, particularly in the nasopharyngeal area, respiratory tract, and head and neck region. Such neoplasms of the kidney in patients with a human immunodeficiency virus (HIV) infection are extremely rare. PATIENT CONCERNS: A 55-year-old male who had been diagnosed with HIV 1 year previously presented with a 2-week history of intermittent right abdominal pain and gross hematuria. DIAGNOSES: Ultrasonography and computed tomography detected a mass that occupied the upper half of the right kidney. A clinical diagnosis of a renal tumor was suspected. INTERVENTIONS: The patient subsequently underwent a retroperitoneal radical nephrectomy. The postoperative pathological diagnosis was solitary EMP of the kidney. Adjuvant radiation therapy was provided at doses of 50 Gy in 20 fractions. OUTCOMES: Currently, the patient is alive and disease free at 7 months postoperatively. To the best of our knowledge, this is the first case of a primary renal EMP in a patient with HIV. LESSONS: The present case illustrates that this rare type of solitary EMP associated with acquired immune deficiency syndrome can occur in the kidney. Additionally, although rare, solitary EMP should be considered in the differential diagnosis of a renal mass in HIV-infected patients.


Asunto(s)
Infecciones por VIH/complicaciones , Neoplasias Renales/complicaciones , Plasmacitoma/complicaciones , Terapia Combinada , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Nefrectomía , Plasmacitoma/diagnóstico , Plasmacitoma/diagnóstico por imagen , Plasmacitoma/terapia , Tomografía Computarizada por Rayos X , Ultrasonografía
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