RESUMEN
Hyperoside is a natural flavonol glycoside widely found in plants and has been reported to have a variety of pharmacological effects, including anticancer abilities. In this study, we demonstrated for the first time that hyperoside inhibited the proliferation of bladder cancer cells in vitro and in vivo. Moreover, hyperoside could not only induce cell cycle arrest, but also induce apoptosis of a few bladder cancer cells. Quantitative proteomics, bioinformatics analysis and Western blotting confirmed that hyperoside induced the overexpression of EGFR, Ras and Fas proteins, which affects a variety of synergistic and antagonistic downstream signaling pathways, including MAPKs and Akt, ultimately contributing to its anticancer effects in bladder cancer cells. This study reveals that hyperoside could be a promising therapeutic strategy for the prevention of bladder cancer.
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Quercetina/análogos & derivados , Transducción de Señal , Neoplasias de la Vejiga Urinaria , Humanos , Puntos de Control del Ciclo Celular , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Apoptosis , Carcinogénesis/genética , Receptores ErbB/genética , Proliferación Celular , Línea Celular TumoralRESUMEN
Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.
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Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1) , Células Madre Pluripotentes Inducidas , Sirtuina 3 , Animales , Ratones , Cardiotoxicidad/metabolismo , Gemcitabina , Homeostasis , Células Madre Pluripotentes Inducidas/metabolismo , Mitocondrias/metabolismo , Miocitos Cardíacos , Oxidación-Reducción , Sirtuina 3/genética , Quinasa 1 Reguladora del Ciclo Celular (Checkpoint 1)/metabolismoRESUMEN
Cardiac hypertrophy, as one of the major predisposing factors for chronic heart failure, lacks effective interventions. Exploring the pathogenesis of cardiac hypertrophy will reveal potential therapeutic targets. S-nitrosylation is a kind of posttranslational modification that occurs at active cysteines of proteins to mediate various cellular processes. We here identified heat shock protein 90 (Hsp90) as a highly S-nitrosylated target in the hearts of rodents with hypertrophy, and the role of Hsp90 in cardiac hypertrophy remains undefined. The S-nitrosylation of Hsp90 (SNO-Hsp90) levels were elevated in angiotensin II (Ang II)- or phenylephrine (PE)-treated neonatal rat cardiomyocytes (NRCMs) in vitro as well as in cardiomyocytes isolated from mice subjected to transverse aortic constriction (TAC) in vivo. We demonstrated that the elevated SNO-Hsp90 levels were mediated by decreased S-nitrosoglutathione reductase (GSNOR) expression during cardiac hypertrophy, and delivery of GSNOR adeno-associated virus expression vectors (AAV9-GSNOR) decreased the SNO-Hsp90 levels to attenuate cardiac hypertrophy. Mass spectrometry analysis revealed that cysteine 589 (Cys589) might be the S-nitrosylation site of Hsp90. Delivery of the mutated AAV9-Hsp90-C589A inhibited SNO-Hsp90 levels and attenuated cardiac hypertrophy. We further revealed that SNO-Hsp90 led to increased interaction of glycogen synthase kinase 3ß (GSK3ß) and Hsp90, leading to elevated GSK3ß phosphorylation and decreased eIF2Bε phosphorylation, thereby aggravating cardiac hypertrophy. Application of GSK3ß inhibitor TWS119 abolished the protective effect of Hsp90-C589A mutation in Ang II-treated NRCMs. In conclusion, this study demonstrates a critical role of SNO-Hsp90 in cardiac hypertrophy, which may be of a therapeutic target for cardiac hypertrophy treatment.
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Cardiomegalia , Insuficiencia Cardíaca , Angiotensina II/metabolismo , Angiotensina II/farmacología , Animales , Cardiomegalia/patología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Insuficiencia Cardíaca/metabolismo , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Ratas , Transducción de SeñalRESUMEN
Cardiac fibrosis (CF) is an irreversible pathological process that occurs in almost all kinds of cardiovascular diseases. Phosphorylation-dependent activation of c-Jun N-terminal kinase (JNK) induces cardiac fibrosis. However, whether S-nitrosylation of JNK mediates cardiac fibrosis remains an open question. A biotin-switch assay confirmed that S-nitrosylation of JNK (SNO-JNK) increased significantly in the heart tissues of hypertrophic patients, transverse aortic constriction (TAC) mice, spontaneously hypertensive rats (SHRs), and neonatal rat cardiac fibroblasts (NRCFs) stimulated with angiotensin II (Ang II). Site to site substitution of alanine for cysteine in JNK was applied to determine the S-nitrosylated site. S-Nitrosylation occurred at both Cys116 and Cys163 and substitution of alanine for cysteine 116 and cysteine 163 (C116/163A) inhibited Ang II-induced myofibroblast transformation. We further confirmed that the source of S-nitrosylation was inducible nitric oxide synthase (iNOS). 1400 W, an inhibitor of iNOS, abrogated the profibrotic effects of Ang II in NRCFs. Mechanistically, SNO-JNK facilitated the nuclear translocation of JNK, increased the phosphorylation of c-Jun, and induced the transcriptional activity of AP-1 as determined by chromatin immunoprecipitation and EMSA. Finally, WT and iNOS-/- mice were subjected to TAC and iNOS knockout reduced SNO-JNK and alleviated cardiac fibrosis. Our findings demonstrate an alternative mechanism by which iNOS-induced SNO-JNK increases JNK pathway activity and accelerates cardiac fibrosis. Targeting SNO-JNK might be a novel therapeutic strategy against cardiac fibrosis.
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Fibrosis/patología , Cardiopatías/patología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Angiotensina II/farmacología , Animales , Aorta/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Humanos , Iminas/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico Sintasa de Tipo II/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Transducción de Señal/efectos de los fármacosRESUMEN
We retrospectively studied the diagnosis and treatment of a case of AAD misdiagnosed as stroke since atypical symptoms as the first manifestation, and discussed the clinical features and manifestations, diagnosis, and differential diagnosis of the case in the context of relevant domestic and international literature. The patient, a 49year-old male with herpes zoster for more than 1 month, presented with sudden onset of right-sided chest and back pain, accompanied by numbness and weakness of the left limb, and was tentatively diagnosed with post-herpetic neuralgia combined with stroke due to the history of herpes zoster. Non-specific ST-T alterations, D-dimer 20ugâ/âml, and non-traumatic angiographic findings in the transthoracic and abdominal aorta demonstrated slight thickening of the patient's ascending aorta, and the lumen of the root sinus region showed intimal flap formation with a larger pseudocoel and smaller true lumen, which ultimately confirmed the diagnosis of acute aortic coarctation with atypical presentation. So clinicians need to improve their basic theoretical knowledge, strengthen the understanding of AAD, focus on physical examination, improve relevant auxiliary examinations expeditiously, and pay attention to the significance of specific auxiliary examinations in order to decrease misdiagnosis and missed diagnosis of atypical manifestations of AAD patients.
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Disección Aórtica , Discinesias , Herpes Zóster , Accidente Cerebrovascular , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico , Disección Aórtica/cirugía , Dolor de Espalda/complicaciones , Discinesias/complicaciones , Herpes Zóster/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/complicacionesRESUMEN
Small double-stranded RNAs (dsRNAs) have been proved to effectively up-regulate the expression of particular genes by targeting their promoters. These small dsRNAs were also termed small activating RNAs (saRNAs). We previously reported that several small double-stranded RNAs (dsRNAs) targeting the PRKC apoptosis WT1 regulator (PAWR) promoter can up-regulate PAWR gene expression effectively in human cancer cells. The present study was conducted to evaluate the antitumor potential of PAWR gene induction by these saRNAs in bladder cancer. Promisingly, we found that up-regulation of PAWR by saRNA inhibited the growth of bladder cancer cells by inducing cell apoptosis and cell cycle arrest which was related to inhibition of antiapoptotic protein Bcl-2 and inactivation of the NF-κB and Akt pathways. The activation of the caspase cascade and the regulation of cell cycle related proteins also supported the efficacy of the treatment. Moreover, our study also showed that these saRNAs cooperated with cisplatin in the inhibition of bladder cancer cells. Overall, these data suggest that activation of PAWR by saRNA may have a therapeutic benefit for bladder cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Proteínas Reguladoras de la Apoptosis/agonistas , ARN Bicatenario/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/genética , Línea Celular Tumoral , Cisplatino/farmacología , Cisplatino/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Humanos , Regiones Promotoras Genéticas/genética , ARN Bicatenario/uso terapéutico , Activación Transcripcional/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: We sought to investigate epidemiologic features of Kawasaki disease (KD) in Shanghai from 2013 through 2017 and identify risk factors for coronary artery lesions (CAL). METHODS: As in our previous three surveys, a set of questionnaires and diagnostic guidelines for KD were sent to 50 hospitals providing pediatric medical care in Shanghai. Medical records of KD patients diagnosed from January 2013 through December 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify risk factors for CAL. RESULTS: A total of 4,452 cases were enrolled. Male-to-female ratio was 1.7:1. The incidence of KD was 68.8 to 107.3 per 100,000 children aged <5 years from 2013 to 2017. Age at onset ranged from 15 days to 14.0 years (median: 1.8 years). KD occurred more frequently in spring and summer. Of 4,325 patients (97.0%) receiving intravenous immunoglobulin (IVIG), 362 (8.4%) were resistant to initial IVIG. CAL occurred in 406 (9.1%) patients, including 118 (2.7%) with medium aneurysms and 31 (0.7%) with giant aneurysms. Recurrent cases were 60 (1.3%). No death was found in this survey. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were independently associated with CAL. CONCLUSIONS: The incidence of KD in Shanghai had substantially increased while the proportion of CAL had substantially decreased as compared with our previous surveys. Higher platelet levels, lower albumin levels, male sex, incomplete KD, IVIG resistance, and receiving initial IVIG ≤4 days or >10 days, were risk factors for CAL.
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Enfermedad de la Arteria Coronaria/epidemiología , Síndrome Mucocutáneo Linfonodular/epidemiología , Adolescente , Edad de Inicio , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Incidencia , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Estudios Retrospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 µmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 µmol/g). In addition, the practicality of the SiO2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.
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Ácidos Borónicos/química , Glicoproteínas/química , Nanocompuestos/química , Dióxido de Silicio/química , Adsorción , Clara de Huevo/química , Estructura Molecular , Tamaño de la Partícula , Dióxido de Silicio/síntesis química , Propiedades de SuperficieRESUMEN
OBJECTIVE: To explore the value of artificial intelligence combined with multi-parametric MRI (AI-mpMRI) in the early diagnosis of prostate cancer. METHODS: This retrospective study included 64 cases of prostate cancer confirmed by biopsy and treated by radical prostatectomy from May 2017 to February 2018. The mpMRI images of T2 weighted imaging (T2WI), diffusion weighted imaging (DWI) and dynamic-contrast enhanced (DCE) MRI and the pathological sections corresponding to the three sequential MRI images were collected. The benign and malignant regions were labeled on the pathological slice level, the three sequential MRI axial images at the same level were virtually covered with the pathological slice using computer-aided transparent mapping technology, and selected the fixed-sized benign and malignant regions of interest (ROI). The MATLAB software was used to display the features of the images and screen out the characteristic parameters with P < 0.05, so as to derive high-accuracy analytical methods for the diagnosis of prostate cancer. RESULTS: A total of 31 image characteristics were extracted with the MATLAB software, and 3 high-accuracy analytical methods screened out for the diagnosis of prostate cancer, including the linear discrimination, logistic regression analysis, and support vector machine classification, with the accuracy rates of 75.9%, 75.4% and 74.9% and the areas under the curve (AUC) of 0.83, 0.82 and 0.82, respectively. CONCLUSIONS: AI-mpMRI can achieve a high detection rate in the early diagnosis of prostate cancer and therefore has a high clinical application value.
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Inteligencia Artificial , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Medios de Contraste , Detección Precoz del Cáncer , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: The aim of this study was to investigate the ability of Pref-1+ adipocyte progenitor cells to mobilize into mesenteric lymph nodes (MLNs) and the dynamic expression of related chemokines during the development of rat MLNs. METHODS: Immunohistochemical analyses were used to detect the expression of Pref-1 and related chemokines. Transmission electron microscopy (TEM) was used to observe the changes in ultrastructure of MLNs. RESULTS: Cells containing lipid droplets were found in all rat MLNs at embryonic day (E) 18.5, 2 and 6 weeks (w) after birth, and they were similar to fibroblastic reticular cells (FRCs) or follicular dendritic cells (FDCs) under TEM. Pref-1+ adipocyte progenitor cells were found in all MLNs. The expression level of Pref-1 was significantly increased at 2 w after birth and decreased at 6 w after birth. The tendency of Cxcl12 expression was consistent with that of Pref-1 and was positively correlated with the expression of Pref-1 (P < 0.01; r = 0.897). At E18.5, Cxcl13, and Ccr7 were significantly expressed in the MLN anlage, but the expression level of Ccl21 was low. The expression level of Cxcl13, Ccr7, and Ccl21 in MLN were significantly increased at 2 w after birth (P < 0.05), while the expression of Ccr7 and Ccl21 were significantly decreased at 6 w after birth (P < 0.05). CONCLUSION: Adipocyte progenitor cells are involved in the rat MLNs development through differentiation into FRC and FDC. The expression of the relevant chemokines during the development of MLNs is dynamic and may be related to the maintenance of lymph nodes self-balance state.
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Quimiocinas/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ganglios Linfáticos/metabolismo , Proteínas de la Membrana/metabolismo , Mesenterio/embriología , Animales , Quimiocinas/genética , Femenino , Péptidos y Proteínas de Señalización Intercelular/genética , Ganglios Linfáticos/embriología , Proteínas de la Membrana/genética , Embarazo , RatasRESUMEN
OBJECTIVE: To analyze the clinical features,response to therapy and prognosis of intravascular large B-cell lymphoma (IVLBCL). METHODS: The clinical data of 17 cases with IVLBCL were retrospectively reviewed,and survival analysis was conducted. RESULTS: The study involved 10 males and 7 females of IVLBCL with a mean age of 53 years old. The most common symptom of the disease was recurrent fever (76.5%). The lymphoma was mainly observed in bone marrow (64.7%) and was clinically determined as stage â £B (70.6%). Many of the patients were also diagnosed with the hemophagocytic syndrome (29.4%). R-CHOP (rituximab,cyclophosphamide,epirubicin,vindesine,prednisone) or CHOP regimen chemotherapy significantly improved the survival of the patients (P=0.000 2). Unfortunately,those patients with bone marrow involvement were prone to relapse after treatment. CONCLUSION: IVLBCL is highly invasive and associated with poor prognosis. R-CHOP chemotherapy can significantly improve the prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Prednisona/uso terapéutico , Pronóstico , Estudios Retrospectivos , Rituximab , Vincristina/uso terapéuticoRESUMEN
Diabetes and its complications continue to be an increasing global health problem. Hydrogen sulfide (H2S)has emerged as the third gasotransmitter following the nitric oxide and carbon monoxide in the body, and plays an important role in both physiology and pathophysiology. Recent work has suggested important roles for H2S in the regulation of pancreatic ß-cell function, as well as development of insulin resistance and diabetic complications. Targeting H2S represents a novel therapeutic approach in diabetes and its associated complications. This review article summarizes the current body of evidence regarding the role of H2S in diabetes mellitus, and especially in its associated vascular complications, as well as the underlying signaling mechanisms.
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Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Sulfuro de Hidrógeno/metabolismo , Monóxido de Carbono , Humanos , Óxido NítricoRESUMEN
BACKGROUND Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities. MATERIAL AND METHODS We used different concentrations of JA and JB (20 µg/ml, 40 µg/ml, 60 µg/ml, 80 µg/ml, and 100 µg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs). RESULTS We found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide. CONCLUSIONS Our results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer.
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Adenocarcinoma Bronquioloalveolar/tratamiento farmacológico , Diterpenos/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Células A549 , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patología , Animales , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To explore the diagnosis, treatment, and prognosis of prostatic malignant mesenchymal tumors (PMMT). METHODS: We retrospectively analyzed the clinical and follow-up data about 20 cases of PMMT and reviewed the literature relevant to the diagnosis, treatment, and prognosis of the disease. RESULTS: Based on the results of pathology and immunohistochemistry, the 20 PMMT cases included leiomyosarcoma (n = 7), rhabdomyosarcoma (n = 5), prostatic stromal sarcoma (n = 3), chondrosarcoma (n = 1), and undifferentiated PMMT (n = 4). Twelve of the patients were treated by radical prostatectomy (3 concurrently by sigmoid colostomy and 1 by cystostomy), 2 by pelvic tumor resection following arterial embolization, 1 by total pelvic exenteration, 1 by colostomy with pelvic lymph node biopsy, and 4 by conservative therapy because of metastasis to the lung, pelvis and bone. Of the 20 patients, 9 died of systemic metastasis within 3 months after treatment, 3 died at 6, 7, and 14 months, respectively, 3 survived with tumor for 5, 11, and 12 months, respectively, 2 survived without tumor for 12 and 24 months so far, all subjected to periodic chemotherapy postoperatively, and 3 lost to follow-up. CONCLUSION: PMMT is a tumor of high malignancy and rapid progression, for which transrectal ultrasound-guided biopsy remains the main diagnostic method. The clinical stage of the tumor is an important factor influencing its prognosis and the survival rate of the patients can be improved by early diagnosis and combined therapy dominated by radical prostatectomy.
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Mesenquimoma/patología , Mesenquimoma/terapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Terapia Combinada/métodos , Humanos , Inmunohistoquímica , Masculino , Mesenquimoma/mortalidad , Pronóstico , Prostatectomía , Neoplasias de la Próstata/mortalidad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the pathogenesis and treatment of penile necrosis resulting from microwave diathermy following circumcision. METHODS: We retrospectively analyzed the clinical data about 9 cases of penile necrosis resulting from postoperative microwave diathermy following circumcision. The 9 males, aged 20 - 39 (mean 26) years, underwent traditional circumcision for redundant prepuce or phimosis in other hospitals, followed by microwave diathermy for 30 - 60 minutes daily, which resulted in penile necrosis. With no response to conservative therapy, the patients were referred to our hospital at 3 -30 days postoperatively. Of the 9 patients, 5 presented with dry gangrene and 4 with moist gangrene. Six of the patients underwent partial penectomy, including 1 that received penis lengthening.3 months later, while the other 3 underwent total penectomy for total penile necrosis followed by penile reconstruction 3 months later, with deep inferior epigastric perforator (DIEP) flaps and by implantation of the 12th costal cartilage in 2 cases and with epigastric groin island flaps and by urethroplasty in the other. RESULTS: The patients were followed up for 2 - 8 years, and all could urinate smoothly in the standing position. Of the 6 men treated by partial penectomy, 1 received penis lengthening and achieved a penile length of 7 cm and 5 had the remaining penile length of 3 -5 cm, 4 with erectile function and the other 2 capable of sexual intercourse. The 3 men treated by total penectomy achieved nearly normal external appearance of the penis, with a finalized length of (11.7 ± 1.3) cm, a circumference of (11.4 ± 2.1) cm, and a normal feel of the skin. Of the 3 cases of penile reconstruction, 2 achieved sufficient erectile hardness of the penis (grade 3) for sexual intercourse, while the other 1 remained impotent. CONCLUSION: Post-circumcision microwave diathermy may result in penile necrosis, for the management of which, early debridement is necessitated and penile lengthening or reconstruction can be performed according to the severity of the lesion and needs of the patient.
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Circuncisión Masculina/métodos , Diatermia/efectos adversos , Microondas/efectos adversos , Adulto , Coito , Cartílago Costal/trasplante , Diatermia/métodos , Humanos , Masculino , Pene/anomalías , Pene/cirugía , Fimosis/cirugía , Periodo Posoperatorio , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: Tea is supposed to have chemopreventive effect against various cancers. However, the protective role of tea in prostate cancer is still controversial. The aim of this study is to elucidate the association between tea consumption and prostate cancer risk by meta-analysis. METHODS: A total of 21 published articles were retrieved via both computerized searches and review of references. Estimates of OR/RR for highest versus non/lowest tea consumption levels were pooled on the basis of random effect model or fixed effect model as appropriate. Stratified analyses on tea type, population and study design were also conducted. RESULTS: No statistical significance was detected between tea consumption and prostate cancer risk in meta-analysis of all included studies (odds ratio (OR) = 0.86, 95% CI (0.69-1.04)). Furthermore, stratified analyses on population (Asian, OR = 0.81, 95% CI (0.55-1.08); non-Asian, OR = 0.89, 95% CI (0.72-1.07)) and tea type (green tea, OR = 0.79, 95% CI (0.43-1.14); black tea, OR = 0.88, 95% CI (0.73-1.02)) also yielded non-significant association. Only the case-control study subgroup demonstrated a borderline protective effect for tea consumption against prostate cancer (OR = 0.77, 95% CI (0.55-0.98)). CONCLUSION: Our analyses did not support the conclusion that tea consumption could reduce prostate cancer risk. Further epidemiology studies are needed.
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Neoplasias de la Próstata/prevención & control , Té , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/etiología , Factores de RiesgoRESUMEN
BACKGROUND: Epidemiological studies of the association between nonsteroidal anti-inflammatory drug (NSAID) intake and the risk of prostate cancer still remain controversial. Therefore, we conducted a meta-analysis to evaluate the potential association between NSAID intake and prostate cancer risk. METHODS: Eligible studies were retrieved by both computerized searches and reviews of references. Subgroup analyses on country and design of study were also performed. Random or fixed-effect models were used to pool estimates of odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We observed that the intake of aspirin was associated with a marginally decreased risk of prostate cancer (OR = 0.95, 95% CI = 0.93 to 0.98). A similar result was found between nonaspirin NSAIDs and prostate cancer risk (OR = 0.94, 95% CI =0.90 to 0.98). However, a positive relation between all-NSAID intake and prostate cancer risk was observed (OR = 1.18, 95% CI = 1.15 to 1.22). CONCLUSIONS: We observed a marginally inverse correlation between the intake of aspirin and prostate cancer risk. On the contrary, a positive relationship between all-NSAID intake and prostate cancer was detected. Further research needs to be conducted to better clarify potential biological mechanisms.
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Antiinflamatorios no Esteroideos/uso terapéutico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/prevención & control , Humanos , Incidencia , Masculino , Pronóstico , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Introduction: Laparoscopic radical prostatectomy (LRP) has become a common option for the treatment of prostate cancer. The aim of our study was to examine whether LRP performed within 12 weeks of transurethral resection of the prostate (TURP) is associated with surgical difficulty or outcomes. Material and methods: A single-institutional retrospective analysis was performed on patients who underwent LRP for incidental prostate cancer after TURP between July 2009 and December 2017. The interval between TURP and LRP was determined and patients with intervals of ≤ 12 weeks were compared to those with intervals of > 12 weeks. Patient characteristics, perioperative, pathological, and postoperative functional outcomes were analyzed to determine statistically significant differences between the 2 groups. Multivariable analyses were performed to determine whether the interval between TURP and LRP was a significant independent predictor of these outcomes. Results: A total of 56 incidental prostate cancer patients detected by TURP were included in this study. No significant differences were detected in estimated blood loss, operative duration, postoperative length of stay, and rate of positive margin, Gleason score upgrading, major complications, incontinence and prostate-specific antigen (PSA) recurrence in patients with a TURP to LRP interval above and below 12 weeks. The TURP to LRP interval was not an independent predictor of outcomes during or after LRP. Conclusions: Our results showed that performing LRP within 12 weeks after TURP does not adversely influence surgical difficulty or outcomes.
RESUMEN
Prostate cancer causes numerous male deaths annually. Although great progress has been made in the diagnosis and treatment of prostate cancer during the past several decades, much about this disease remains unknown, especially its pathobiology. The kinesin superfamily is a pivotal group of motor proteins, that contains a microtubule-based motor domain and features an adenosine triphosphatase activity and motility characteristics. Large-scale sequencing analyses based on clinical samples and animal models have shown that several members of the kinesin family are dysregulated in prostate cancer. Abnormal expression of kinesins could be linked to uncontrolled cell growth, inhibited apoptosis and increased metastasis ability. Additionally, kinesins may be implicated in chemotherapy resistance and escape immunologic cytotoxicity, which creates a barrier to cancer treatment. Here we cover the recent advances in understanding how kinesins may drive prostate cancer progression and how targeting their function may be a therapeutic strategy. A better understanding of kinesins in prostate cancer tumorigenesis may be pivotal for improving disease outcomes in prostate cancer patients.