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1.
Eur Rev Med Pharmacol Sci ; 28(5): 1640, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38497848

RESUMEN

Correction to: Eur Rev Med Pharmacol Sci 2020; 24 (12): 6605-6615-DOI: 10.26355/eurrev_202006_21646-published online on June 25, 2020. After publication, the authors have applied some corrections to the galley proof: -       In Table II, data display in MMP14 expression between Low and high group was inverted. This correction does not involve any statistical data modification and does not affect the conclusion of the article. The correct table display should be as follows: -       In Figure 4F, the cell invasion image of siRNA-2 group in T24 was misplaced. The authors have adjusted the brightness and contrast appropriately as well. The correct Figure 4F display should be as follows: There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21646.

2.
Osteoporos Int ; 34(9): 1613-1623, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37247006

RESUMEN

This study involving 674 elderly osteoporotic fracture (OPF) patients undergoing orthopedic surgery investigated the long-term outcomes of acute phase reaction (APR) after initial zoledronic acid (ZOL). Those who had an APR had a 97% higher risk of mortality and a 73% lower rate of re-fracture than patients who did not. INTRODUCTION: Annual infusion of ZOL efficiently decreases the risk of fracture. A temporary APR, consisting of flu-like symptoms, myalgia, and fever, is frequently observed within 3 days after the first dose. This work aimed to identify whether the occurrence of APR after initial ZOL infusion is a reliable indicator of drug efficacy for mortality and re-fracture in elderly OPF patients undergoing orthopedic surgery. METHODS: This retrospectively observed work was constructed on a database prospectively collected from the Osteoporotic Fracture Registry System of a tertiary level A hospital in China. Six hundred seventy-four patients 50 years old or older with newly identified hip/morphological vertebral OPF who received ZOL for the first time after orthopedic surgery were included in the final analysis. APR was identified as a maximum axillary body temperature greater than 37.3 °C for the first 3 days after ZOL infusion. We utilized models of multivariate Cox proportional hazards to compare the risk of all-cause mortality in OPF patients with APR (APR+) and without APR (APR-). Competing risks regression analysis was used to examine the association between the occurrence of APR and re-fracture when mortality was taken into account. RESULTS: In a fully adjusted Cox proportional hazards model, APR+ patients had a significantly higher risk of death than APR- patients with a hazard ratio [HR] 1.97 (95% CI, 1.09-3.56; P-value = 0.02). Furthermore, in an adjusted competing risk regression analysis, APR+ patients had a significantly reduced risk of re-fracture compared with APR- patients with a sub-distribution HR, 0.27 (95% CI, 0.11-0.70; P-value = 0.007). CONCLUSIONS: Our findings suggested a potential association between the occurrence of APR and increased mortality risk. An initial dose of ZOL following orthopedic surgery was found to be protective against re-fracture in older patients with OPFs.


Asunto(s)
Conservadores de la Densidad Ósea , Fracturas Osteoporóticas , Anciano , Humanos , Persona de Mediana Edad , Reacción de Fase Aguda/inducido químicamente , Conservadores de la Densidad Ósea/efectos adversos , Fracturas Osteoporóticas/epidemiología , Estudios Retrospectivos , Ácido Zoledrónico/efectos adversos
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(5): 846-852, 2022 Oct 18.
Artículo en Chino | MEDLINE | ID: mdl-36241227

RESUMEN

OBJECTIVE: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. METHODS: Cdh16-Cre tool mice and Kindlin-2flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. RESULTS: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. CONCLUSION: Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Vía de Señalización Hippo , Proteínas Quinasas Activadas por AMP/metabolismo , Adenosina Monofosfato/metabolismo , Animales , Cadherinas/metabolismo , Proteínas del Citoesqueleto/metabolismo , Endometrio/metabolismo , Eosina Amarillenta-(YS)/metabolismo , Femenino , Hematoxilina/metabolismo , Masculino , Mamíferos/metabolismo , Ratones , Proteínas Musculares , Proteína S6 Ribosómica/metabolismo , Sirolimus/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Señalizadoras YAP
4.
Zhonghua Yi Xue Za Zhi ; 101(46): 3789-3793, 2021 Dec 14.
Artículo en Chino | MEDLINE | ID: mdl-34895418

RESUMEN

Objective: To investigate the feature of immune cells infiltration in inherited renal carcinoma with von Hippel-Lindau (VHL) syndrome and their relationship with clinicopathological characteristics and prognosis. Methods: The samples were collected from patients with VHL syndrome renal carcinoma who were diagnosed and treated surgically at the Department of Urology, Peking University First Hospital from 2010 to 2019. RNA-Seq was performed on 6 pairs of VHL syndrome renal carcinoma and adjacent normal tissues. To identify the specific infiltrated immune cells, RNA-Seq data was converted into the infiltration data of 14 types of immune cells using the TIP tool. Immunohistochemical staining was used to verify the expression of the markers of these specific infiltrated immune cells in the paraffin sections of 54 paired VHL syndrome renal carcinoma and adjacent normal tissues, and to analyze their relationship with clinicopathological characteristics and prognosis. Results: Compared with adjacent normal tissues, CD4 Naive infiltration level was significantly down-regulated (0.289±0.009 vs 0.200±0.012,P<0.001) and CD4 Memory infiltration level was significantly up-regulated (0.123±0.014 vs 0.222±0.016,P<0.001) in VHL syndrome renal carcinoma. Immunohistochemical staining results showed that CD45RA (a CD4 Naive cell marker) expression was significantly reduced (50.9±1.9 vs 15.6±0.9,P<0.001) and CD45RO (a CD4 Memory cell marker) expression was significantly increased (22.2±1.1 vs 80.8±4.3,P<0.001) in VHL syndrome renal carcinoma. Besides, lower CD45RA expression and higher CD45RO expression were associated with higher histological grade, advanced tumor stage and shorter disease-free survival (all P<0.01). In addition, CD45RA expression was positively correlated with VHL expression (r=0.693 3, P<0.000 1) and CD45RO expression was negatively correlated with VHL expression (r=-0.609 0, P<0.000 1). Conclusions: This study found that CD4 Naive and CD4 Memory cells may be differentially infiltrated immune cells in VHL syndrome renal carcinoma, and their infiltration levels were associated with the expression of VHL and the prognosis of patients.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Enfermedad de von Hippel-Lindau , Humanos , Pronóstico , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética
5.
Zhonghua Yi Xue Za Zhi ; 101(46): 3784-3788, 2021 Dec 14.
Artículo en Chino | MEDLINE | ID: mdl-34895417

RESUMEN

Objective: To analyze the epidemiological, clinicopathological and prognostic characteristics of clear cell papillary renal cell carcinoma (CCPRCC) based on Chinese patient population. Method: Patients with renal cell carcinoma diagnosed at Peking University First Hospital from June 2016 to June 2020 were included in this study based on the inclusion and exclusion criteria. All cases were grouped according to CCPRCC, clear cell renal cell carcinoma (ccRCC), and papillary renal cell carcinoma (pRCC), and the general clinical, postoperative pathological and follow-up data of the patients were retrospectively analyzed. Result: A total of 18 CCPRCC patients were enrolled in this study, accounting for 0.44% (18/4 110) of the postoperative pathologically confirmed renal cell carcinoma cases in our hospital during this time period. The age range of the included patients was 28-86 years old, with a median age of 49.5 years old. There were 11/18 males and 7/18 females. All CCPRCC patients had no family history of renal malignant tumors. Among them, only one patient with CCPRCC had related clinical symptoms, that was intermittent waist and abdomen pain, while the other 17 cases were found by physical examination without any related symptoms. Compared with ccRCC and pRCC, there was no significant difference in their end stage renal disease history(χ2ccRCC=0.291, χ2pRCC=1.161,all P>0.05). The maximum diameter of CCPRCC tumor was smaller than pRCC (χ2=-2.280,P =0.027) but not significantly different from ccRCC (χ2=-0.579,P =0.565). The majority of patients with CCPRCC were in pT1, their pathological stage was earlier than the other two types, and their overall survival was better than ccRCC and pRCC (P<0.05). Conclusion: CCPRCC is a type of renal cell carcinoma with unique epidemiology, clinicopathology and prognostic characteristics. Patients with this subtype have an earlier clinical stage and a better prognosis than ccRCC and pRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos
6.
Eur Rev Med Pharmacol Sci ; 24(23): 12116-12123, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33336729

RESUMEN

OBJECTIVE: To illustrate the role of microRNA-1231 (miR-1231) in regulating malignant proliferative potential and DTX sensitivity to gallbladder carcinoma (GBC) by regulating FOXC2 level. PATIENTS AND METHODS: Expression levels of miR-1231 in GBC tissues and paracancerous ones were detected. The relationship between miR-1231 level and clinical parameters of GBC patients was analyzed. After overexpression of miR-1231, changes in proliferative and apoptotic potentials in GBC-SD and NOZ cells were examined by Cell Counting Kit-8 (CCK-8), colony formation assay and flow cytometry, respectively. Regulatory effects of miR-1231 on its downstream gene FOXC2 were determined by Luciferase assay. Finally, the role of miR-1231 in regulating DTX sensitivity to GBC cells was assessed. RESULTS: MiR-1231 was downregulated in GBC tissues compared to paracancerous ones. GBC patients expressing lower level of miR-1231 had worse tumor staging and larger tumor size. Overexpression of miR-1231 attenuated proliferative potential, and induced apoptosis in GBC cells. FOXC2 was upregulated in GBC and negatively linked to miR-1231. Luciferase activity confirmed that FOXC2 was the target gene binding miR-1231. DTX treatment dose-dependently suppressed viability in GBC cells and overexpression of miR-1231 could enhance DTX sensitivity in GBC. Notably, overexpression of FOXC2 abolished regulatory effects of overexpressed miR-1231 on proliferative and apoptotic potentials in GBC cells. CONCLUSIONS: MiR-1231 is downregulated in GBC species. Its level is closely linked to tumor staging and tumor size in GBC patients. By downregulating FOXC2, miR-1231 enhances DTX sensitivity to GBC cells and thus alleviates the malignant development of GBC.


Asunto(s)
Regulación hacia Abajo , Factores de Transcripción Forkhead/metabolismo , Neoplasias de la Vesícula Biliar/metabolismo , MicroARNs/metabolismo , Proliferación Celular , Femenino , Factores de Transcripción Forkhead/genética , Neoplasias de la Vesícula Biliar/patología , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Células Tumorales Cultivadas
7.
Eur Rev Med Pharmacol Sci ; 24(12): 6605-6615, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32633349

RESUMEN

OBJECTIVE: To evaluate the short-term prognostic value of matrix metalloproteinase 14 (MMP14) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Expression of MMP14 and clinical information from The Cancer Genome Atlas (TCGA) were mined in MIBC patients to analyse expression differences and conduct survival analyses. The mRNA and protein expression levels of MMP14 in other tumours were analysed using Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas. The expression level of MMP14 in bladder cancer (BC) cell lines and clinical samples and its clinical significance were indicated using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), Western blotting, and immunohistochemistry. The biological functions of MMP14 were investigated by examining cell migration using in vitro wound-healing assays and cell invasion using transwell invasion assays. Survival analyses were conducted with the collected clinical follow-up data. RESULTS: Our study revealed that MMP14 is highly expressed in MIBC based, on both TCGA derived data and our clinical tissues (p<0.05). MMP14 is also highly expressed in head and neck cancer, renal cancer, pancreatic cancer and other cancers, as analysed using GEPIA and The Human Protein Atlas (p<0.05). Survival analyses of the TCGA data and our clinical follow-up data revealed high expression of MMP14 indicates a poor short-term prognosis in MIBC (p<0.05). Furthermore, downregulation of MMP14 suppressed BC cell invasion and migration abilities in vitro. MMP14 expression was closely correlated with tumour metastasis (p<0.05). T stage [hazard ratio (HR)=1.412, 95% confidence interval (CI)=1.121-1.779, p=0.003] and metastasis (HR=2.256, 95% CI=1.242-4.100, p=0.008) were unfavourable prognostic factors in BC patients. CONCLUSIONS: In MIBC, MMP14 expression is upregulated and closely associated with disease progression and poor short-term prognosis.


Asunto(s)
Biomarcadores de Tumor/biosíntesis , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 14 de la Matriz/biosíntesis , Neoplasias de Tejido Muscular/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Biomarcadores de Tumor/genética , Línea Celular Transformada , Línea Celular Tumoral , Femenino , Humanos , Masculino , Metaloproteinasa 14 de la Matriz/genética , Persona de Mediana Edad , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Neoplasias de Tejido Muscular/genética , Neoplasias de Tejido Muscular/patología , Neoplasias de Tejido Muscular/secundario , Pronóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología
9.
Zhonghua Wai Ke Za Zhi ; 56(3): 227-230, 2018 Mar 01.
Artículo en Chino | MEDLINE | ID: mdl-29534419

RESUMEN

Objective: To study the clinical characteristics, image findings, therapeutic method and prognosis of metanephric adenoma. Method: The clinical characteristic, image findings, operation methods and prognosis of 16 metanephric adenoma patients treated at Department of Urology, Peking University First Hospital from January 2004 to March 2016 were analyzed retrospectively. Results: There were 6 male and 10 female patients in the study. The mean age of patients was 33.7 years (ranging from 14 to 83 years). Two patients came to the hospital because of fever, while other 14 patients had no symptoms and found renal tumor by medical examination. One case was found polythemia vera and another 1 case showed mild anemia. Serum creatine of all the cases were in normal range. The tumor of 11 cases were at left side and 5 cases were at right. All patients took urinary tract ultrasound. Fifteen patients took CT examination. Among them, 14 cases were solid mass and 1 case was cystosolid.CT value was (41±4) HU. CT scan showed that the tumor was slight enhanced and CT value increased to (77±9) HU. Six patients took MRI examination. The MRI showed high or low signal of T1WI or T2WI scans.Tumor size was (4.7±3.9)cm (ranging from 1.7 to 17.5 cm). All 16 patients took operation and 11 of them took laparoscopic surgery while the other 5 cases took open surgery. Eleven cases took partial nephrectomy, 4 cases took nephrectomy and 1 case took nephroureterectomy. The surgical procedures were all successful and no complications occured during perioperative period. All cases were all confirmed metanephric adenoma by postoperative pathology and surgery cut edge were all negative. Immunohistochemical study showed that the positive rate of Vimentin, CD57, AE1/AE3, WT1, CK7 and AMACR respectively were 16/16, 15/16, 12/16, 10/16, 3/16 and 2/16. The median follow-up time of 16 cases was 44 months (ranging from 8 to 125 months) and none had recurrence or metastasis.One case died 125 months after surgery because of advanced age(83 years old). Conclusions: Metanephric adenoma is difficult to be diagnosed relying on clinical characteristics and image features. Pathology can help confirm the diagnosis. Partial nephrectomy is the first choice for operation and can achieve good prognosis. But it still needs a regular follow-up.


Asunto(s)
Adenoma , Neoplasias Renales , Adenoma/diagnóstico , Adenoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nefrectomía , Estudios Retrospectivos , Adulto Joven
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 49(4): 569-574, 2017 08 18.
Artículo en Chino | MEDLINE | ID: mdl-28816267

RESUMEN

OBJECTIVE: To investigate the mechanisms of nuclear export signal of androgen receptor (NESAR) in the regulation of androgen receptor (AR) protein expression and stability in prostate cancer. METHODS: The green fluorescent protein fusion protein expression vectors pEGFP-AR(1-918aa), pEGFP-NESAR (743-817aa), pEGFP-NAR (1-665aa) and pEGFP-NAR-NESAR, and lysine mutants of NESAR pEGFP-NESAR K776R, pEGFP-NESAR K807R and pEGFP-NESAR K776R/K807R, were transiently transfected into prostate cancer cell line PC3. Fluorescence microscopy, Western blot and immunoprecipitation were used to detect NESAR regulation of androgen receptor stability. RESULTS: Under the fluorescence microscope, NESAR-containing fusion proteins were cytoplasmic localization, and their fluorescence intensities were much weaker than those without NESAR. The expression levels of NESAR-containing fusion proteins were significantly lower than those without NESAR. The half-lives of GFP-NESAR and GFP-NAR-NESAR were less than 6 h, while the expression of GFP and GFP-NAR was relatively stable and the half-life was more than 24 h in the presence of cycloheximide. The expression levels of GFP-NESAR were significantly increased by proteasome inhibitor MG132 treatment in a dose-dependent manner; in contrast, MG132 did not show any significant effect on the protein levels of GFP. When new protein synthesis was blocked, MG132 could also prevent the degradation of GFP-NESAR in the transfected cells in the presence of cycloheximide, while it had no significant effect on GFP protein stability in the parallel experiment. GFP immunoprecipitation showed that the ubiquitination level of GFP-NESAR fusion protein was significantly higher than that of the GFP control. The mutations of lysine sites K776 and K807 in NESAR significantly reduced the level of ubiquitination, and showed increased protein stability, indicating that they were the key amino acid residues of NESAR ubiquitination. CONCLUSION: NESAR was unstable and decreased the stability of its fusion proteins. NESAR was the target of polyubiquitination and mediated the degradation of its fusion proteins through the ubiquitin-proteasome pathway in prostate cancer cells. Our research provides a new way to regulate the level and/or activity of AR proteins, thus helping us understand the molecular mechanisms of AR degradation and strict control of AR in the progression to castration-resistance.


Asunto(s)
Señales de Exportación Nuclear , Neoplasias de la Próstata , Receptores Androgénicos , Andrógenos , Línea Celular Tumoral , Humanos , Masculino , Señales de Exportación Nuclear/fisiología , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/fisiología
11.
Eur J Cancer ; 40(10): 1554-65, 2004 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15196540

RESUMEN

This study evaluated the anti-angiogenic activities of erianin in vivo and in vitro. Erianin, a natural product from Dendrobium chrysotoxum, caused moderate growth delay in xenografted human hepatoma Bel7402 and melanoma A375 and induced significant vascular shutdown within 4 h of administering 100 mg/kg of the drug. Erianin also displayed potent anti-angiogenic activities in vitro: it abrogated spontaneous or basic fibroblast growth factor-induced neovascularisation in chick embryo; it inhibited proliferation of human umbilical vein endothelial cells (EC(50) 34.1+/-12.7 nM), disrupted endothelial tube formation, and abolished migration across collagen and adhesion to fibronectin. Erianin also exerted selective inhibition toward endothelial cells, and quiescent endothelium showed more resistance than in proliferative and tumour conditions. In a cytoskeletal study, erianin depolymerised both F-actin and beta-tubulin, more significantly in proliferating endothelial cells than in confluent cells. In conclusion, erianin caused extensive tumour necrosis, growth delay and rapid vascular shutdown in hepatoma and melanoma models; it inhibited angiogenesis in vivo and in vitro and induced endothelial cytoskeletal disorganisation. These findings suggest that erianin has the therapeutic potential to inhibit angiogenesis in vivo and in vitro.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Bibencilos/uso terapéutico , Carcinoma Hepatocelular/irrigación sanguínea , Neoplasias Hepáticas/irrigación sanguínea , Melanoma/irrigación sanguínea , Neoplasias Cutáneas/irrigación sanguínea , Células 3T3 , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Femenino , Neoplasias Hepáticas/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Fenol , Neoplasias Cutáneas/tratamiento farmacológico , Células Tumorales Cultivadas
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