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2.
Clin Radiol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38589276

RESUMO

AIM: To evaluate the motion amplitude of lung nodules in different locations during preoperative computed tomography (CT)-guided localization, and the influence of respiratory movement on CT-guided percutaneous lung puncture. MATERIALS AND METHODS: A consecutive cohort of 398 patients (123 men and 275 women with a mean age of 53.9 ± 10.7 years) who underwent preoperative CT-guided lung nodule localization from May 2021 to Apr 2022 were included in this retrospective study. The respiratory movement-related nodule amplitude in the cranial-caudal direction during the CT scan, characteristics of patients, lesions, and procedures were statistically analyzed. Univariate and multivariate logistic regression analyses were used to evaluate the influence of these factors on CT-guided localization. RESULTS: The nodule motion distribution showed a statistically significant correlation within the upper/middle (lingular) and lower lobes (p<0.001). Motion amplitude was an independent risk factor for CT scan times (p=0.011) and procedure duration (p=0.016), but not for the technical failure rates or the incidence of complications. Puncture depth was an independent risk factor for the CT scan times, procedure duration, technical failure rates, and complications (p<0.01). Female, prone, and supine (as opposed to lateral) positions were significant protective factors for pneumothorax, while the supine position was an independent risk factor for parenchymal hemorrhage (p=0.025). CONCLUSION: Respiratory-induced motion amplitude of nodules was greater in the lower lobes, resulting in more CT scan times/radiation dose and longer localization duration, but showed no statistically significant influence on the technical success rates or the incidence of complications during preoperative CT-guided localization.

3.
Zhonghua Gan Zang Bing Za Zhi ; 32(1): 58-63, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38320792

RESUMO

Objective: To explore the clinicopathological and molecular genetic features of adult hepatic mesenchymal hamartoma (MHL). Methods: A total of five confirmed adult MHL cases diagnosed at the Pathology Department of the First Medical Center of the People's Liberation Army General Hospital between 2009 and 2022 were collected. Histomorphological observation and immunohistochemical staining were conducted. Gene detection was performed by next-generation sequencing. Results: Among the five cases, four were male and one was female, aged 46-67 years, with an average age of 56.2 years. The maximum diameter was 5.3-13.5cm, and the average diameter was 9.2cm. Tumors were generally cystic, solid, or mixed cystic-solid. Histopathologically, in four out of five cases of MHL, malignant transformation occurred, of which three cases were malignantly transformed into undifferentiated embryonal sarcoma and one case was malignantly transformed into a malignant solitary fibrous tumor. NAB2-STAT6 gene rearrangements were identified. Conclusion: Adult MHL is a rare kind of tumor with malignant potential, and it is difficult to diagnose with preoperative imaging examinations. A fine-needle biopsy is rarely used for diagnosis, but surgical resection of symptomatic or enlarged lesions is recommended to rule out the possibility of malignancy and further diagnosis. Genetic testing results revealed the complex genetic alterations in MHL, and it was found that adult MHL can malignantly transform into malignant solitary fibrous tumors. We believe that genome-wide analysis is necessary to determine the unique molecular characteristics of MHL and identify potential targets for therapeutic intervention.


Assuntos
Hamartoma , Neoplasias Hepáticas , Sarcoma , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/patologia , Sarcoma/genética , Sarcoma/patologia , Hamartoma/diagnóstico , Hamartoma/patologia , Hamartoma/cirurgia , Mutação , Biomarcadores Tumorais
4.
Zhonghua Bing Li Xue Za Zhi ; 53(2): 168-173, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38281785

RESUMO

Objective: To investigate the clinicopathological and molecular genetic characteristics of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) with myxoid-like morphology, and to distinguish them from myxofibrosarcoma (MFS) with similar morphology. Methods: Twenty-nine cases of myxoid-like liposarcoma and 5 cases of MFS were collected from Henan Provincial People's Hospital, Zhengzhou, China and the First Medical Center of PLA General Hospital, Beijing, China from January 2015 to March 2023. Relevant markers were detected using immunohistochemistry and fluorescence in situ hybridization (FISH). The literature was also reviewed. Results: There were 24 males and 10 females, with ages ranging from 41 to 73 years. The tumor sites included retroperitoneum (n=17), abdomen (n=9), lower limbs (n=5), scrotum (n=1), upper limb (n=1) and axilla (n=1). WDLPS was commonly seen as lipomatoid type (12 cases), while the dedifferentiated components of DDLPS included low-grade (13 cases) and high-grade (2 cases) morphology, with low-high grade myxofibrosarcoma, dermatofibrosarcoma protuberans, and low-grade fibrosarcoma structures. Twenty-nine liposarcomas had various proportions of myxoid-like morphology, while 16 showed various degrees of tumor necrosis. The myxoid-like component showed myxoid pleomorphic liposarcoma (MLPS)-like morphology, lobulated growth, characteristic slender, ramified capillary network,"chicken claw-like"morphology, mucus-rich stroma and lung edema-like morphology. Tumor cells were spindle and oval, with many variable vacuolar lipoblasts. MDM2 gene amplification was detected using FISH and present in all tested cases (29/29). DDIT3 break-apart mutation was not detected, but its cluster amplification was present (24/29). Among the MFS cases, one showed cluster amplification (1/5), but no cases showed break-apart or amplification of MDM2 gene. Conclusions: WDLPS/DDLPS with myxoid-like morphology is most commonly seen in the retroperitoneum and abdominal cavity and mostly harbors DDIT3 break-apart probe amplification, while this amplification is not specific to liposarcoma. For core biopsy specimens or very rare tumors in the limbs, when histology has mucinous stroma and MLPS-like morphology, misdiagnosis of MLPS or other non-lipomatous neoplasms with myxoid morphology should be avoided.


Assuntos
Fibrossarcoma , Lipoma , Lipossarcoma Mixoide , Lipossarcoma , Masculino , Feminino , Adulto , Humanos , Hibridização in Situ Fluorescente , Lipossarcoma/patologia , Lipoma/patologia , Biologia Molecular , Proteínas Proto-Oncogênicas c-mdm2/genética , Lipossarcoma Mixoide/genética , Lipossarcoma Mixoide/patologia
6.
Zhonghua Yi Xue Za Zhi ; 103(19): 1490-1495, 2023 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-37198112

RESUMO

Objective: To investigate the clinical efficacy of Hintermann osteotomy (H-LCL) for flexible flatfoot. Methods: A follow-up study. Clinical data of 30 patients with flexible flatfoot treated with H-LCL operation from January 2020 to December 2021 in Sports Medical Center of the First Affiliated Hospital of Army Medical University were retrospectively analyzed. There were 8 males and 22 females, with a mean age of (39.0±15.2) years. The mean time from symptom onset to the diagnosisï¼»M(Q1,Q3)]was 24.0 (5.5, 102.0) months. The functional and imaging scores of the patients before and after the last follow-up were compared to evaluate the clinical efficacy of the operation. The functional scores included American Orthopedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) of pain, pain interference (PI) and physical function (PF) index in Patient-Reported Outcomes Measurement Information System (PROMIS). And the imaging scores included Meary's angle, calcaneal pitch angle, calcaneal valgus angle and talonavicular coverage angle. Results: The mean operation time was (82.3±24.4) min, and the follow-up periods was (17.9±6.9) months. At the last follow-up, VAS of pain [M(Q1, Q3)] decreased from 5 (4, 6) to 2 (1, 2); PI decreased from 59.8±5.0 to 44.6±5.7; AOFAS increased from 65.2±10.0 to 85.8±3.3; PF increased from 50 (48.5,51.0) to 58.5 (54.0, 66.0); Meary's angle (antero-posterior image) decreased from 15.7° (10.1°, 29.2°) to 3.9° (2.6°, 5.3°); Meary's angle (lateral image) decreased from 13.5°±6.8° to 4.4°±2.6°; calcaneal pitch angle increased from 14.0°±3.3° to 18.6°±4.2°; calcaneal valgus angle decreased from 12.6°±7.3° to 4.3°±2.5°; and talonavicular coverage angle decreased from 20.9°±10.7° to 7.7°±5.2°. The up-mentioned parameters were all improved statistically significant at the last follow-up when compared with those before the operation (all P<0.05). Conclusion: H-LCL brings a significant improvement of clinical outcome scores and good radiological correction of flatfoot deformities in correcting flexible flatfoot, it conforms to the anatomical characteristics of the subtalar joint.


Assuntos
Calcâneo , Pé Chato , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Pé Chato/cirurgia , Seguimentos , Estudos Retrospectivos , Osteotomia/métodos , Calcâneo/cirurgia , Dor
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(1): 29-38, 2023 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-36856207

RESUMO

OBJECTIVE: To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection. METHODS: The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs. RESULTS: A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01). CONCLUSION: DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.


Assuntos
Autofagia , Dengue , Células Endoteliais da Veia Umbilical Humana , Proteoma , Humanos , Morte Celular , Núcleo Celular , Células Endoteliais da Veia Umbilical Humana/virologia
11.
Clin Transl Oncol ; 21(10): 1327-1335, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30762207

RESUMO

PURPOSE: Glioma is a common malignant tumor of the central nervous system, which is characterized by a low cure rate, high morbidity, and high recurrence rate. Consequently, it is imperative to explore some indicators for prognostic prediction in glioma. METHODS: We obtained glioma data from The Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) were obtained by R software from TCGA data sets. Through Cox regression analysis, risk scores were obtained to assess the weighted gene-expression levels, which could predict the prognosis of patients with glioma. The validity and the prognostic value of this model in glioma were confirmed by the manifestation of receiver-operating characteristic (ROC) curves, area under the curve (AUC), and 5-year overall survival (OS). RESULTS: In total, 920 DEGs of transcriptome genes in glioma were extracted from the TCGA database. We identified a novel seven-gene signature associated with glioma. Among them, AL118505.1 and SMOC1 were positively related to the 5-year OS of patients with glioma, showing a better prognosis for glioma; however, RAB42, SHOX2, IGFBP2, HIST1H3G, and IGF2BP3 were negatively related to 5-year OS, displaying a worse prognosis. In addition, according to risk scores, AL118505.1 was also a protective factor, while others were risk factors. Furthermore, the expression levels of SHOX2, IGFBP2, and IGF2BP3 were significantly positively correlated with glioma grades. Receiver-operating characteristic (ROC) curve assessed the accuracy and sensitivity of the gene signature. Each of the seven genes for patients with the distribution of the risk score was presented in the heat map. CONCLUSION: We identified a novel seven-gene signature in patients with glioma, which could be used as a predictor for the prognosis of patients with glioma in the future.


Assuntos
Neoplasias Encefálicas/genética , Expressão Gênica , Genes Neoplásicos , Glioma/genética , Área Sob a Curva , Neoplasias Encefálicas/mortalidade , Glioma/mortalidade , Proteínas de Homeodomínio/genética , Humanos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteínas de Neoplasias/genética , Osteonectina/genética , Prognóstico , Proteínas de Ligação a RNA/genética , Curva ROC , Análise de Regressão , Risco , Transcriptoma
12.
Artigo em Chinês | MEDLINE | ID: mdl-30669205

RESUMO

Mucinous adenocarcinoma is most commonly found in the digestive tract,and the prognosis is poor.We present here a case of primary mucinous adenocarcinoma of the larynx, which is an extremely rare entity and very few have been reported in the literature.A 72-year-old male complained of intermittent hoarseness for over 2 months of duration.Fiberoptic laryngoscope showed negative result for tumor.While CT scan showed laryngeal space occupying lesion,and thyroid cartilage damage was observed.The patient underwent total laryngectomy.Histopathological examination and immunohistochemistry(IHC) analysis supported the diagnosis of mucinous adenocarcinoma.

13.
Zhonghua Bing Li Xue Za Zhi ; 47(9): 691-695, 2018 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-30220123

RESUMO

Objective: To investigate clinicopathologic features and prognosis of adenoid cystic carcinoma (ACC) involving external auditory meatus. Methods: The clinical presentation and follow-up data of 63 patients with ACC of external auditory canal were collected from January 2006 to February 2017 at PLA General Hospital and Hainan Branch of PLA General Hospital. The clinicopathologic features and prognostic factors of external auditory canal ACC were analyzed. Results: (1) There were 28 males and 35 females and the average age of the first diagnosis was 48.9 years (22-81 years). The tumors showed cribriform pattern in 35 cases (15 cases of late stage), tubular pattern in 14 cases (8 cases of late stage), and solid pattern in 14 cases (9 cases of late stage). Cases with solid pattern was relatively more frequent than that of cribriform pattern and tubular pattern, but the difference was not statistically significant (P>0.05). (2) The average follow-up time was 62.4 months (2-228 months) in the 57 available cases. Among the 33 cases with recurrence, 18 cases had local recurrence and 15 cases had distant metastasis. The mean recurrence time was 40.6 months (2-204 months). Nine patients died of ACC: 2 cases in early stage (died at 48 and 102 months after the first treatment), 7 cases in late stage and 57 with (died at 9, 30, 32, 60, 72, 94 and 228 months). (3) Among the 37 patients with perineural invasion, there were 21 cases of cribriform pattern, 4 cases of tubular pattern and 12 cases of solid pattern; the number of cases in early stage and late stage were 15 and 22, respectively; and the differences were statistically significant (P<0.05). In addition, 31 cases had otalgia among the 37 patients with perineural invasion, where differences were not significant (P>0.05). (4) Thirty of 45 cases with tumor resection or partial resection of temporal bone had recurrence, whereas 3 of 12 cases of tumor combined with superficial lobectomy of parotid gland had recurrence. The difference was statistically significant (P<0.05). Postoperative adjuvant radiotherapy was given in 19 cases, including 7 cases of early stage (2 cases of recurrence), and 12 cases of late stage (8 cases of recurrence), among which there was no significant difference (P>0.05). Conclusions: ACC occurring in external auditory canal frequently recurs. Superficial parotid lobectomy at the first operation is necessary to prevent tumor recurrence. Postoperative adjuvant radiotherapy has certain curative effect on patients with early stage tumor, but it does not affect the recurrence rate. Patients at late stage are more prone to perineural invasion than those in early stage. In addition, cribriform and solid patterns are more common that tubular pattern, and there is no significant correlation between perineural invasion and otalgia.


Assuntos
Carcinoma Adenoide Cístico/patologia , Neoplasias da Orelha/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/secundário , Carcinoma Adenoide Cístico/terapia , Meato Acústico Externo , Neoplasias da Orelha/mortalidade , Neoplasias da Orelha/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Glândula Parótida/cirurgia , Prognóstico , Fatores de Tempo , Adulto Jovem
14.
Zhonghua Bing Li Xue Za Zhi ; 47(7): 536-541, 2018 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29996320

RESUMO

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.


Assuntos
Porocarcinoma Écrino/patologia , Tumor Misto Maligno/patologia , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Diagnóstico Diferencial , Porocarcinoma Écrino/química , Epitélio , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Tumor Misto Maligno/química , Mioepitelioma/química , Mioepitelioma/patologia , Proteínas Proto-Oncogênicas c-kit/análise , Neoplasias Cutâneas/química , Neoplasias das Glândulas Sudoríparas/química
15.
Neoplasma ; 65(2): 242-252, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29534586

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer in adults. The aim of this study is to identify the biomarkers and potential molecular mechanisms of ccRCC. Three gene expression profiles and two miRNA expression profiles were downloaded from GEO database. A total of 330 up-regulated differentially expressed genes (DEGs), 545 down-regulated DEGs, 26 up-regulated differentially expressed miRNAs (DEMs) and 11 down-regulated DEMs were identified by GEO2R. The gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by KOBAS software. The results showed that GO terms of the up-regulated DEGs were mostly enriched in response to stimulus at BP level, cell periphery at CC level and binding at MF level, while the GO terms of down-regulated DEGs were enriched in single-organism process at BP level, extracellular exosome at CC level and catalytic activity at MF level. As for KEGG pathways, HIF-1 signaling pathway, focal adhesion, PI3K-Akt signaling pathway and metabolic pathways were significantly enriched. Then, protein-protein interaction (PPI) network and miRNA-gene network were constructed and analyzed by Cytoscape. A total of eight DEGs were identified as biomarkers, including VEGFA, PPARA, CCND1, FLT1, CXCL12, FN1, DCN and ERBB4. Expression validation and survival analysis were performed by GEPIA and OncoLnc, respectively. Four biomarkers were verified by quantitative real-time PCR (qPCR) in 786-O cell line and HK-2 cell line. All four genes had the same expression trend as predicted. Our study provides a series of biomarkers and molecular mechanisms for the deeper research of ccRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , MicroRNAs/genética , Transdução de Sinais
16.
Neoplasma ; 64(5): 674-680, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28592119

RESUMO

Resistance to anticancer agents such as Epirubicin (EPI) becomes a great challenge for treating bladder cancer. However, the mechanism by which chemoresistance arised is still elusive. In the present study, we showed evidence that EPI induced cytoprotective autophagy in bladder cancer cell lines T24 and BIU87. In addition, EPI robustly activated JNK-mediated phosphorylation of Bcl-2 and disruption of Bcl-2/Beclin-1 complex. Furthermore, the green tea derivative tea polyphenol (TP) inhibited EPI-induced autophagy and promoted apoptosis induced by EPI in bladder cancer cells. These results revealed a pathway for EPI-induced autophagy that involved in JNK/Bcl-2/Beclin-1 in bladder cancer cells, and that TP synergistically promoted EPI-induced apoptosis at least partly through autophagy inhibition. Thus, TP could be utilized in combination with EPI to improve EPI-based bladder cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Epirubicina/farmacologia , Polifenóis/farmacologia , Chá/química , Neoplasias da Bexiga Urinária/patologia , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico
17.
J Endocrinol Invest ; 38(10): 1117-28, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26036598

RESUMO

INTRODUCTION: Long-acting somatostatin analogs (SSAs) are most widely used to treat growth hormone (GH)-secreting pituitary adenoma. However, approximately 30 % of treated patients show resistance to SSAs, which may be associated with the reduction of somatostatin receptor subtype 2 (SSTR2) mRNA and protein expression. MATERIALS AND METHODS: The present study used immunohistochemistry to detect the expression of SSTR2 and SSTR5 in twenty human GH-secreting adenoma samples treated with SSAs and seven normal pituitary samples. RESULTS: The staining intensities of SSTR2 and SSTR5 were stronger in most adenoma samples than in normal pituitary. The expression of SSTR2 tended to be lower in the SSA non-responder group than in responders. A search of the Bioinformatics data bank and the miRCURY™ LNA array confirmed miR-185 as the putative mircoRNA (miRNA) regulating the expression of SSTR2. An in vitro study using Dual Luciferase reporter assay demonstrated that miR-185 likely targets the 3'-UTR of SSTR2 mRNA in the rat pituitary adenoma GH3 cell line. MiR-185 also downregulated or upregulated the expression of SSTR2 mRNA and SSTR2 protein, following transfection with miR-185 mimics or inhibitors, respectively. CONCLUSION: MiR-185 enhanced the cell proliferation and inhibited the apoptosis of GH3 cells.


Assuntos
Adenoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , MicroRNAs/metabolismo , Receptores de Somatostatina/metabolismo , Adenoma/genética , Adenoma/patologia , Adulto , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Ratos
18.
Int J Lab Hematol ; 36(5): 555-65, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24460694

RESUMO

INTRODUCTION: Previous studies have indicated that a deletion on the short arm of chromosome 1 negatively predicts survival in patients with multiple myeloma (MM). Due to the small sample size in each study, we performed this meta-analysis to comprehensively investigate the association between the 1p deletion and survival in patients with MM. METHODS: A literature search was conducted in both foreign and Chinese databases, including SinoMed, CNKI, Wanfang, PubMed, EMBASE, and Scopus. Hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS) in 11 eligible articles were extracted or calculated to analyze the pooled HR, which was estimated by fixed-effect or random-effect models based on the heterogeneity between included articles. A subgroup analysis and a meta-regression were conducted, and Galbraith plots were generated to examine any possible heterogeneity. RESULTS: The HRs for OS were available in nine articles, whereas five articles discussed HRs for PFS. The HR with 95%CI was 1.989 (95%CI 1.522-2.600, P = 0.017, I(2)  = 57.1%) when comparing the OS of patients with 1p deletion with the OS of those without this deletion. For PFS, 1p deletion still predicted a poor prognosis (HR 2.11, 95%CI 1.54-2.88, P = 0.292, I(2)  = 19.3%). Moreover, the subgroup analysis suggested that either the deleted gene on 1p or techniques for detecting chromosome abnormalities contributed to the heterogeneity, which was partially consistent with the results derived from a meta-regression analysis and the Galbraith plot method. CONCLUSION: Our meta-analysis provides globally quantifiable confirmation of the adverse prognostic role of 1p deletion in OS and PFS for patients with MM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Deleção Cromossômica , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Cromossomos Humanos Par 1 , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
19.
Oncogene ; 33(23): 3004-13, 2014 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-23831571

RESUMO

Killing cancer cells through the induction of apoptosis is one of the main mechanisms of chemotherapy. However, numerous cancer cells have primary or acquired apoptosis resistance, resulting in chemoresistance. In this study, using a novel chalcone derivative chalcone-24 (Chal-24), we identified a novel anticancer mechanism through autophagy-mediated necroptosis (RIP1- and RIP3-dependent necrosis). Chal-24 potently killed different cancer cells with induction of necrotic cellular morphology while causing no detectable caspase activation. Blocking the necroptosis pathway with either necrostatin-1 or by knockdown of RIP1 and RIP3 effectively blocked the cytotoxicity of Chal-24, suggesting that Chal-24-induced cell death is associated with necroptosis. Chal-24 robustly activated JNK and ERK and blockage of which effectively suppressed Chal-24-induced cytotoxicity. In addition, Chal-24 strongly induced autophagy that is dependent on JNK-mediated phosphorylation of Bcl-2 and Bcl-xL and dissociation of Bcl-2 or Bcl-xL from Beclin-1. Importantly, suppression of autophagy, with either pharmacological inhibitors or small interfering RNAs targeting the essential autophagy components ATG7 and Beclin-1, effectively attenuated Chal-24-induced cell death. Furthermore, we found that autophagy activation resulted in c-IAP1 and c-IAP2 degradation and formation of the Ripoptosome that contributes to necroptosis. These results thus establish a novel mechanism for killing cancer cells that involves autophagy-mediated necroptosis, which may be employed for overcoming chemoresistance.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Chalconas/farmacologia , Proteínas Inibidoras de Apoptose/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Proteína 7 Relacionada à Autofagia , Proteína 3 com Repetições IAP de Baculovírus , Proteína Beclina-1 , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imidazóis/farmacologia , Indóis/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Proteínas de Ligação a RNA/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Enzimas Ativadoras de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases
20.
Int J Impot Res ; 25(6): 206-11, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23595104

RESUMO

Diabetes mellitus (DM)-associated ED is predominantly due to neurovascular dysfunction mediated by nitric oxide (NO) suppression. Panax notoginseng saponins (PNS) are widely used for treating cardiovascular disease in China. The aim of this study was to evaluate the effects of PNS on penile erection and corpus cavernosum tissues in rats with diabetes-associated ED. Four weeks after PNS treatment, erectile function was assessed by intracavernous pressure (ICP) and mean arterial pressure (MAP) measurements. The level of NO, cyclic guanosine monophosphate (cGMP) and advanced glycation end products (AGEs) in cavernous tissue were assessed. Immunohistochemical staining and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) were performed for detecting endothelial NO synthase (eNOS) and apoptosis, respectively. The results show that ICP/MAP ratio was significantly increased in high-dose (150 mg kg(-1) per day) PNS-treated group compared with the diabetic ED untreated group (DM group). Compared with the untreated group, the expression of eNOS and the levels of NO and cGMP were increased in the PNS-treated groups. Moreover, apoptosis was markedly decreased in the group that received 150 mg kg(-1) per day of PNS. These results suggest that PNS may be used for improving the ED in diabetic rats via the NO/cGMP pathway and restores the function of endothelium in corpus cavernosum.


Assuntos
Diabetes Mellitus Experimental/complicações , Endotélio Vascular/efeitos dos fármacos , Disfunção Erétil/tratamento farmacológico , Panax notoginseng/química , Pênis/irrigação sanguínea , Saponinas/uso terapêutico , Animais , Apoptose , Pressão Sanguínea , GMP Cíclico/análise , Endotélio Vascular/fisiopatologia , Disfunção Erétil/etiologia , Produtos Finais de Glicação Avançada/análise , Marcação In Situ das Extremidades Cortadas , Masculino , Óxido Nítrico/análise , Óxido Nítrico Sintase Tipo III/análise , Pênis/química , Pênis/inervação , Pressão , Ratos , Ratos Sprague-Dawley
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