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1.
Zhonghua Yi Xue Za Zhi ; 104(7): 540-546, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38317367

RESUMO

Objective: To establish an acute graft-versus-host disease (aGVHD) model in aged mice after non-myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PSCT). Methods: C57BL/6 (H-2b) male mice aged 6-8 weeks were used as donor mice, and CB6F1 (H-2b×d) female mice aged 14-16 months were used as recipient mice. The donor mice were injected subcutaneously with rehuman granulocyte-colony stimulating factor (rhG-CSF) 5 days before transplantation for hematopoietic stem cell mobilization.The recipient mice were divided into control group (CG), spleen cell low-dose group (SL), spleen cell medium-dose group (SM) and spleen cell high-dose group (SH) according to random number table method, with 16 rats in each group, all of which received total linear accelerator X-ray irradiation (TBI) with a total dose of 6 Gy. Peripheral blood mononuclear cells (PBMC) and spleen cells of different doses (0.5×107/each, 1.0×107/each and 2.0×107/each in SL group, SM group and SH group, respectively) were transfused through the tail vein within 4 hours after TBI, and only the same amount of normal saline was transfused in CG group. After transplantation, the survival and weight changes of mice in each group were observed for 30 days, and the changes of blood routine were monitored regularly. Mice peripheral blood was collected 21 days after transplantation to detect the chimerism rate of the donor. Hematoxylin-eosin staining was performed on the skin, liver and colon of mice 21 days after transplantation to analyze the histopathological changes of aGVHD target organs. Results: All the mice in each group were successfully transplanted. After TBI, the weight and activity of mice in all groups decreased, and the phenomenon of bone marrow suppression appeared. During the observation period, all mice in CG group and SL group survived, 3 mice in SM group died with survival time of (26.0±5.8) days, and 6 mice in SH group died with survival time of (20.9±7.3) days. The body weight of mice in SH group was lower than that in CG group, SL group and SM group 21days after transplantation [(25.0±0.7), (25.5±0.4), (25.0±1.4) vs (20.8±0.8) g, all P<0.05]. Compared with CG group, SL group and SM group, the levels of leukocyte, erythrocyte, hemoglobin and platelet in SH group decreased 21 days after transplantation (all P<0.05). There was no significant difference in donor chimerism rate among SL group, SM group and SH group [(95.8%±0.8%), (95.5%±1.4%) and (95.1%±1.3%), respectively, all P>0.05]. Compared with CG group, SL group and SM group, the tissue structure of aGVHD target organs in SH group was severely damaged, with a large number of inflammatory cells infiltratedand higher histopathological scores than SL group and SM group (all P<0.05). Conclusion: For aging CB6F1 mice, after 6 Gy TBI pretreatment with linear accelerator X-ray, PBMC (1×107/each) and spleen cells (2.0×107/each) were injected to successfully induce aGVHD model after non-myelablative haplo-PSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Masculino , Feminino , Camundongos , Animais , Ratos , Leucócitos Mononucleares , Camundongos Endogâmicos C57BL , Transplante de Medula Óssea
3.
Eur Rev Med Pharmacol Sci ; 25(3): 1600-1611, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33629329

RESUMO

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.


Assuntos
Hepatite Autoimune/metabolismo , Proteínas com Domínio LIM/metabolismo , Cirrose Hepática/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Hepatite Autoimune/patologia , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Nature ; 587(7832): 63-65, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33149293

RESUMO

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

6.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(11): 1237-1242, 2020 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-33147923

RESUMO

Objective: To analyze the survival time and to explore the releated factors of antiretroviral therapy among HIV/AIDS patients in LiangShan Prefecture, Sichuan Province for reduction of AIDS death rate. Methods: The retrospective research method was used to collect relevant information from the Management Database of Antiviral Treatment from the National AIDS Comprehensive Prevention Information System. The Kaplan-Meier method was used to describe the survival distribution and to analyze the survival time by single factor and the model of Cox proportional riskanalysis was performed to analyze the survival time of HARRT by multi-factors analysis. Results: Total 14 219 adults and young persons aged ≥15 HIV/AIDS patients received antiviral treatment from 2005 to 2015. The average age of all cases was (36.10±9.41) years old and 10 021 were males (70.5%). The main route of infection was intravenous drug use (61.0%, 8 678 cases). At the end of the observation, 10001 cases (70.3%) were still treated, and 1 425 cases (10.0%) died; Cox Regression analysis showed that female (0.67 (0.55-0.81)), route of sexual infection (0.67 (0.56-0.79)), baseline CD4+T lymphocyte count 200-350 (0.41 (0.35-0.47)) and ≥350 (0.28 (0.24-0.34)), was a protective factor in death. At the beginning of treatment, the patient is clinically staging stage Ⅱ (0.70 (0.58-0.84)) and abnormal BMI (1.75 (1.50-2.03)), is a risk factor for death (P<0.05). Conclusion: Early antiviral treatment is of great significance in improving the anti-viral treatment effect of AIDS. Compliance education should be further strengthened so as to enhance their knowledge. And it is feasible to enhance the effect of treatment through nutritional support for prolonging patients survival time and improving the quality of life.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , China , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida
7.
Med Oral Patol Oral Cir Bucal ; 25(6): e714-e719, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33037812

RESUMO

BACKGROUND: To explore the prevalence of dental anxiety (DA) in patients with third molar extractions and its influence factors and the correlation between DA levels and postoperative pain. MATERIAL AND METHODS: A prospective and descriptive clinical study was performed. All patients who underwent the impacted third molar extraction from October 2017 to February 2019 were enrolled. DA levels were assessed by virtue of the modified dental anxiety scale (MDAS) and pain was assessed with a visual analog scale (VAS). RESULTS: A total of 150 patients were investigated and 136 valid questionnaires were retrieved, with an effective rate of 90.7%. The independent sample t-test and ANOVA results showed that the anxiety level of patients with the third molar extractions was statistically different in gender, teeth extraction experience and self-assessment oral health status. Multiple linear regression analysis with DA as a dependent variable showed that gender and teeth extraction experience were independent factors influencing DA in patients with third molar extractions. Pearson's test showed that there was a significant correlation between DA level in patients and the postoperative pain on the first day (r=0.542, p=0.000). CONCLUSIONS: For patients (females, poor oral hygiene and no teeth extraction experience), surgeon should pay more attention to DA of such patients and take measures to reduce the anxiety when removing the third molars. Furthermore, surgeon can recommend oral administration ibuprofen sustained release capsules after surgery.


Assuntos
Dente Serotino , Dente Impactado , Ansiedade ao Tratamento Odontológico/epidemiologia , Feminino , Humanos , Dente Serotino/cirurgia , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Extração Dentária , Dente Impactado/cirurgia
9.
Zhonghua Yi Xue Za Zhi ; 100(15): 1159-1163, 2020 Apr 21.
Artigo em Chinês | MEDLINE | ID: mdl-32311880

RESUMO

Objective: To discuss the diagnostic value potential of (18)F-FDG PET/CT and intravoxel incoherent motion (IVIM) in genotype EGFR of lung cancer. Methods: A total of 116 cases proved pathologically pulmonary space occupying lesions (72 males, 44 females; age range was 31-85 years; 37 cases of high differentiation; 53 cases of middle differentiation, 26 cases of low differentiation) were prospectively collected from August 2017 to March 2019 in Henan Provincial People's Hospital. EGFR gene detection was performed in 50 patients (wild type 20 cases, mutant 30 cases). Whole body PET/CT and lung MR-imaging were performed before treatment in all patients. Comparison of PET/CT, IVIM semi-quantitative parameters between positive and negative of EGFR by Student-t test or Mann-Whitney U test. Evaluation diagnostic efficacy of each parameter to EGFR by drawing ROC curves. The optimum diagnostic threshold, specificity, sensitivity, positive predictive value, negative predictive value and the diagnostic accuracy were calculated. The diagnostic accuracy of (18)F-FDG PET/CT combined with IVIM was calculated. Results: The quantitative parameters standard intake(SUV), apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D(*)), perfusion fraction (f) were 8.7±3.5, (1.59±0.26) ×10(-3) mm(2)/s, (1.04±0.12)×10(-3) mm(2)/s, (3.9±3.0)×10(-2) mm(2)/s, 0.43±0.16 and the above parameters of the wild group were 14.3±3.3, (1.34±0.26)×10(-3) mm(2)/s, (0.89±0.12)×10(-3) mm(2)/s, (3.5±2.5)×10(-2) mm(2)/s, 0.40±0.11, respectively. The difference of quantitative parameters SUV (t=4.196, P=0.0001), ADC (t=2.502, P=0.0018), D (t=3.158, P=0.006) between the EGFR mutant group and the wild group was statistically significant. The difference of quantitative parameters D(*) (t=0.361, P=0.721), f (t=0.627, P=0.536) was not statistically significant. ROC curve was drawn and the area under the curves for diagnosis of EGFR mutations by SUV, ADC, D, D(*), f was 0.880, 0.755, 0.820, 0.575, 0.550. The diagnostic accuracy of these parameters above mentioned was 80.0%, 76.7%, 73.3%, 66.7%, 53.3% respectively. The diagnostic accuracy of SUV combined with ADC, D values was 83.3% and 80.0%. Conclusion: PET/CT and IVIM have certain diagnostic value for EGFR typing of lung cancer gene.


Assuntos
Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem de Difusão por Ressonância Magnética , Receptores ErbB , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Eur Rev Med Pharmacol Sci ; 23(24): 10796-10802, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31858547

RESUMO

OBJECTIVE: To illustrate the role of FOXF2 in the aggravation of the progression of non-small cell lung cancer (NSCLC) by targeting long non-coding RNA (lncRNA) H19 to down-regulate the gene of phosphate and tensin homolog deleted on chromosome ten (PTEN). PATIENTS AND METHODS: The relative levels of FOXF2 and H19 in NSCLC tissues and adjacent normal tissues were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expression levels of FOXF2 and H19 was analyzed. Kaplan-Meier curves were depicted for uncovering the prognostic value of FOXF2 in NSCLC patients. The proliferative and migratory abilities of A549 cells influenced by FOXF2 were also assessed. The interaction between FOXF2 and H19 was evaluated through chromatin immunoprecipitation (ChIP) assay and Western blot, so did the association between H19 and PTEN. Finally, rescue experiments were conducted to explore the role of FOXF2/H19/PTEN axis in regulating the viability and migration of A549 cells. RESULTS: FOXF2 and H19 were upregulated in NSCLC and a positive correlation was observed between the two genes. High level of FOXF2 indicated a worse prognosis in NSCLC patients. The knockdown of FOXF2 attenuated the proliferative and migratory abilities of A549 cells. FOXF2 could bind to the promoter region of H19 and accelerated its transcription. Moreover, H19 could recruit EZH2 to bind to PTEN. The overexpression of H19 could reverse the regulatory effects of FOXF2 on the viability and migration of A549 cells. CONCLUSIONS: FOXF2 was upregulated in NSCLC. It accelerated the proliferative and migratory abilities of the NSCLC cells by targeting H19 to downregulate PTEN, thus aggravating the progression of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Neoplasias Pulmonares/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Fatores de Transcrição Forkhead/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/genética , Células Tumorais Cultivadas
11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(9): 1116-1119, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31594156

RESUMO

Objective: To analyze the deaths with antiretroviral treatment among adult HIV/AIDS patients in Liangshan Yi Autonomous Prefecture from 2005 to 2015, in order to understand the epidemiological characteristics and to further reduce the mortality rate in Liangshan Prefecture. Methods: The relevant information was collected through the Management Database of Antiretroviral Treatment from the National AIDS Comprehensive Prevention Information System. Results: From 2005 to 2015, a total of 14 219 adult HIV/AIDS patients received antiretroviral treatment and 1 425 death cases were reported during the treatment. The cause of death was mainly AIDS-related diseases (58.9%), and the cumulative mortality rate was 10.02%. Gender, age, the way of infection, duration of antiretroviral therapy, clinical stage when received antiretroviral therapy, and CD(4)(+) T lymphocyte levels were factors for the mortality rate (P<0.001). The mortality increased with older age, higher initiation clinical stage and lower level of CD(4)(+) T lymphocyte. Among the death cases, 82.6% were male, 1 182 (82.9%) were married or cohabited, most aged between 30-39 years old (48.6%). At the initial point of receiving antiretroviral therapy, 49.7% of the cases with CD(4)(+)T lymphocytes levels< 200/µl, 61.2% of the deaths cases were>1 000 copies/ml during the last viral load test, and 16.2% of deaths were ≥500/µl in the last CD(4)(+)T lymphocyte test; 44.5% of deaths were received antiretroviral treatment within one year. Conclusion: Early and timely antiretroviral therapy should be carried out. It is necessary to strengthen the propaganda of antiretroviral therapy and to improve the management quality of follow-up information of antiretroviral therapy case files, and to improve the medication compliance of patients.


Assuntos
Antirretrovirais , Infecções por HIV/epidemiologia , Adulto , Idoso , China/epidemiologia , Feminino , HIV , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
12.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 667-672, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495134

RESUMO

Objective: To analyze the efficacy of HLA-haploidentical peripheral hematopoietic stem cell transplantation (haplo-PBSCT) following reduced intensity conditioning (RIC) regimen to treat the patients with hematological malignancies who were older than 50 years old. Methods: Eighteen patients with hematological malignancies over 50 years were enrolled, including 8 male and 10 female patients. The median age of all patients was 52 (range: 50-66) years. Of them, 8 patients had acute myeloid leukemia (AML) , 2 chronic myelocytic leukemia (CML) , 5 myelodysplastic syndrome (MDS) , 2 acute lymphoblastic leukemia (ALL) , and 1 aggressive natural killer cell leukemia (ANKL) . All patients received fludarabine, cytarabine and melphalan with rabbit anti-human thymocyte globulin (FAB+rATG regimen) and transplanted with high dose non-T cell-depleted peripheral hematopoietic stem cells from donors. Enhanced graft versus host disease (GVHD) prophylaxis and infection prevention were administered. Results: Fifteen days after transplantation, 16 patients achieved complete donor chimerism. One of them rejected the donor graft completely at thirty days after transplantation, and the other 2 patients had mixed chimerism 15 days after transplantation and converted to complete recipient chimerism at 30 days after transplantation. The cumulative incidence of acute GVHD (aGVHD) was 61.1% (95%CI49.6%-72.6%) . The incidence of grade Ⅱ-Ⅳ aGVHD was 35.4% (95%CI 21.1%-49.7%) , whereas grade III-IV was 13.8% (95%CI 4.7%-22.9%) . The 2-year cumulative incidence of chronic GVHD (cGVHD) rate was estimated at 38.2% (95%CI 25.5%-50.9%) . Patients were followed-up for a median of 14.5 months (range, 3-44 months) . The Kaplan Meier estimates of 2-year overall survival (OS) and disease-free survival (DFS) was 72.6% (95%CI 60.1%-85.1%) and 63.7% (95%CI 49.2%-78.2%) , respectively. The 2-year cumulative incidence of relapse and non-relapse-mortality (NRM) was 31.2% (95%CI 16.5%-45.9%) and 12.5% (95%CI 4.2%-20.8%) , respectively. Conclusion: RIC-haplo-PBSCT protocol can achieve better results in patients with hematologic malignancies over 50 years old.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante
13.
Zhonghua Er Ke Za Zhi ; 57(8): 597-602, 2019 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-31352744

RESUMO

Objective: To study the relationship between human cytomegalovirus (HCMV) envelope glycoprotein gene H and clinical features of children with congenital cytomegalovirus infection. Methods: A cohort study was conducted. Newborns diagnosed with congenital cytomegalovirus infection, hospitalized in the Department of Neonatology and Neonatal Intensive Care Unit (NICU) of the Children's Hospital, Zhejiang University School of Medicine, were included from July 2013 to December 2015.HCMV-DNA gH typing in urine, sputum or blood was conducted. Patients then were divided into gH1 group and gH2 group according to gH genotypes. Patients' data during hospitalization in newborn and 3-5 years of follow-up were collected.The relationships between gH genotype and clinical manifestations, laboratory examinations, hearing loss and neurological prognosis were analyzed by chi-square test, t test and non-parametric test. Results: A total of 21 cases were enrolled as congenital HCMV infection and followed-up for 3-5 years. Among them, 14 (67%) were gH1 type and 7 (33%) were gH2 type. No mixed infection was found. In the two groups, there were no significant differences in the ratio of males (9/14 vs. 3/7,P=0.397), or birth weight ((2 609±686) vs. (3 021±451) g, t=-1.436, P=0.167). Gestational age of gH1 group was younger than that of gH2 group (38 (29-40) vs. 39(38-40) weeks, Z=-2.18, P=0.029). Moderate to severe hearing loss detected by neonatal auditory brainstem response were found in 40 ears (20 cases). It was higher in gH1 group than that in gH2 group (4/22 vs.0/18, χ(2)=5.145, P=0.023). In the imaging examination of the nervous system, the Alarcon score of gH1 group was lower than that of gH2 group (0.4±0.3 vs. 1.3±1.1, t=-2.459,P=0.024).No significant statistical difference was found in the probability of motor or language development lag in gH2 group and gH1 group (4/7 vs.4/14, P=0.346). Conclusions: Compared with gH2 infection, gH1 infection in children has a younger gestational age. The major type of hearing loss in neonatal period is gH1 infection. Children with gH2 congenital infections are more likely to suffer from nervous systems damage.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/virologia , Citomegalovirus/classificação , Citomegalovirus/genética , Proteínas do Envelope Viral/genética , Criança , Estudos de Coortes , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/genética , Primers do DNA , Genótipo , Humanos , Recém-Nascido , Masculino
14.
Eur Rev Med Pharmacol Sci ; 22(16): 5364-5370, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30178863

RESUMO

OBJECTIVE: We aimed to evaluate the effects of fulvestrant on the glycolysis of prolactinoma GH3 cells, and reveal the potential regulatory mechanisms. MATERIALS AND METHODS: Prolactinoma cell line GH3 was treated with different concentrations of fulvestrant (0, 0.12, 0.25, 0.5 and 1 ng/ml) for 4 h. siRNAs XBP1s and XBP1u were constructed to treat GH3 cells. The expression levels of XBP1s, XBP1u, IRE1, PKM2 and GRP78 of GH3 cells were detected by Western blot. Meanwhile, the glycolytic activity of GH3 cells, including the glucose uptake, ATP/ADP, and lactate production were detected. RESULTS: The expression levels of XBP1s and XBP1u were significantly inhibited by fulvestrant in a dose-dependent manner. The glucose uptake, ATP/ADP and lactate production of GH3 cells were significantly inhibited by fulvestrant as well as siRNA XBP1s and XBP1u (p < 0.05). Western blot analysis suggested that the expression levels of IRE1, PKM2 and GRP78 were significantly decreased in GH3 cells treated by fulvestrant as well as siRNA XBP1s and XBP1u, compared with those in normal control (p < 0.05). CONCLUSIONS: Fulvestrant could inhibit the glycolysis of GH3 cells by downregulating IRE1/XBP1 signaling pathway, and this process was closely related with the downregulation of PKM2.


Assuntos
Fulvestranto/farmacologia , Glicólise/efeitos dos fármacos , Prolactinoma/tratamento farmacológico , Animais , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos
16.
Life Sci ; 194: 1-6, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29247745

RESUMO

AIMS: Thymidine kinase 1 (TK1) is a tumor biomarker in human malignancies. The purpose of this study was to evaluate the diagnostic efficiency of this marker for lung cancer using the combined analysis of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), neuron specific enolase (NSE) and TK1. MAIN METHODS: From 2013 to 2014, 147 patients with lung cancer and 228 patients with lung benign diseases who were admitted to our hospital were reviewed. Peripheral blood samples were collected for the detection of TK1, CEA, CYFRA21-1 and NSE. The diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic regression equations. KEY FINDINGS: The serum levels of TK1, CEA, CYFRA21-1 and NSE were significantly higher than those in patients with lung benign diseases (all P<0.05). The TK1 concentration was dependent on TNM stage (P=0.005). The ROC curve analyses showed that the diagnostic value of TK1 combined with CEA, CYFRA21-1 and NSE in lung cancer was significantly higher than that of each biomarker alone (all P<0.0001). In addition, TK1 combined with CEA, CYFRA21-1, or NSE could also improve the diagnosis of the squamous cell carcinoma, adenocarcinoma and small cell lung cancer subtypes, respectively. SIGNIFICANCE: The combined detection of TK1 and the other three markers significantly improved the diagnosis of lung cancer. Furthermore, the detection of TK1 combined with that of CYFRA21-1, CEA or NSE increased the diagnostic value of TK1 for lung squamous cell carcinoma, adenocarcinoma and SCLC, respectively.


Assuntos
Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Queratina-19/sangue , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Fosfopiruvato Hidratase/sangue , Timidina Quinase/sangue , Adenocarcinoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos
17.
Eur Rev Med Pharmacol Sci ; 21(13): 3061-3068, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28742200

RESUMO

OBJECTIVE: To investigate whether hypoxia microenvironment induced hepatocellular carcinoma cells SMMC-7721 epithelial-mesenchymal transition (EMT) and to explore the underlying molecular mechanism. MATERIALS AND METHODS: In this study, SMMC-7721 cells were cultured under normoxia and hypoxia conditions, respectively. RT-PCR and Western blot were used to monitor the expression level of EMT-related markers, E-cadherin, and vimentin, as well as hypoxia inducible factor-1α (HIF-1α) and Twist1. Then we performed the transwell invasion assays to detect the ability of cell invasion. RESULTS: The results demonstrated that hypoxia micro-environment could induce hepatocellular carcinoma cells SMMC-7721 EMT and enhance the cell invasion ability. Furthermore, knockdown of Twist1 by using specific siRNA could reverse hypoxia-induced EMT process. CONCLUSIONS: Hypoxia promotes hepatocellular carcinoma cells SMMC-7721 EMT by upregulating the expression of Twist1.


Assuntos
Hipóxia Celular , Transição Epitelial-Mesenquimal/genética , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ativação Transcricional , Proteína 1 Relacionada a Twist/antagonistas & inibidores , Proteína 1 Relacionada a Twist/genética , Vimentina/genética , Vimentina/metabolismo
19.
Zhonghua Zhong Liu Za Zhi ; 39(3): 184-189, 2017 Mar 23.
Artigo em Chinês | MEDLINE | ID: mdl-28316216

RESUMO

Objective: To evaluate the correlation between computed tomography (CT) features and malignancy risk category of small (≤5 cm) gastric stromal tumors (GST), in order to provide an image reference for preoperative assessment and intraoperative pathological diagnosis. Methods: Eighty-three patients with surgically and pathologically proven GST (≤5 cm) between January 2011 and November 2015 were recruited, and their clinical, pathological and CT data were retrospectively analyzed. According to the pathological results and malignancy risk category, the patients were divided into 2 groups, the benign biological behavior group (very low and low risk) and malignant biological behavior group (intermediate and high risk). The clinical, pathological and CT imaging findings of the two groups were analyzed. Based on the tumor diameter, the receiver operating characteristic curve (ROC) was applied to evaluate the sensitivity, specificity and the best cut-off point for distinguishing the malignancy risk between the two groups. Results: The lobulation and ulceration of the tumors presented statistically significant difference for the malignancy risk between the two groups (χ(2)=6.273 and 4.163, respectively; all P<0.05), but there was no significant difference in the sex, clinical symptoms, serum ferritin, tumor site, growth pattern, cystis degeneration and calcification (all P>0.05). No statistically significant differences were detected for the tumor CT value, arterial CT value, venous CT value, degrees of enhancement in arterial phase (DEAP), enhancement in portal venous phase (DEPP), and patient's age for distinguishing the malignancy risk between the two groups (all P>0.05). On the other hand, significant differences were found in the maximum diameter (Dmax) of tumor and the minimum diameter (Dmin) of tumor (t=-3.256 and -3.466, respectively; all P<0.05). When the cut-off point of Dmax was 1.6 cm, the area under the ROC curve, sensitivity and specificity were 0.704, 92.3% and 75.4%, respectively. When the cut-off point of Dmin was 1.5 cm, the area under the ROC curve, sensitivity and specificity were 0.713, 88.5% and 71.9%, respectively. Conclusion: CT features of the GST (≤5 cm) may predict, before surgery, the malignancy risk of small gastric stromal tumors, and provide the an image reference for preoperative assessment and intraoperative pathological diagnosis of the disease.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Feminino , Tumores do Estroma Gastrointestinal/classificação , Humanos , Masculino , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/classificação , Tomografia Computadorizada por Raios X , Carga Tumoral
20.
Zhonghua Zhong Liu Za Zhi ; 39(2): 139-144, 2017 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-28219211

RESUMO

Objective: To explore the application value of CT imaging in differentiating gastric stromal tumors (GST) from gastric leiomyomas (GLMs). Methods: CT images of patients with GST (n=65) or GLMs (n=13, maximum diameter of tumor ≤5 cm) proved by surgery and pathology were retrospectively analyzed. The tumor size, location, contour, growth pattern, degree and pattern of enhancement, calcification, necrosis, surface ulceration, lymph nodes, and patient clinical data were evaluated by two independent reviewers. Receiver operating characteristic (ROC) curves were employed to assess the measurement and calculation parameters in the differentiation of GST and GLMs. Results: Between the GST and GLMs groups, there was no statistically significant difference in the contour, growth pattern, calcification, surface ulceration, and patient's sex (P>0.05). CT values of in plain scans, degree of enhancement in arterial phase (DE1), size, location and pattern of enhancement were found to be different between GST and GLMs (P<0.05). When the cutoff value of the maximum tumor diameter was 3.2 cm, the area under ROC curve, sensitivity and specificity were 0.707, 92.3%(12/13) and 60.6%(40/66), respectively. When the cutoff value of age was 59 years, the area under ROC curve, sensitivity and specificity were 0.773, 92.3% (12/13) and 46.2% (30/65), respectively. Taking the cutoff value of 10.9 HU as the degree of enhancement in arterial phase (DE1), the area under ROC curve, sensitivity and specificity were 0.774, 84.6% (11/13) and 77.3% (51/66), respectively. Using a cutoff value of 30.3 HU, the sensitivity, specificity, and the area under ROC curve were 84.6% (11/13), 65.2% (43/66), and 0.731, respectively. Conclusions: CT examination in addition to clinical data can be very helpful for the differential diagnosis of GLMs from GSTs in maximum diameter ≤5 cm.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Leiomioma/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Calcinose/diagnóstico por imagem , Calcinose/patologia , Diagnóstico Diferencial , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Leiomioma/patologia , Masculino , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/patologia , Carga Tumoral
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