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2.
Yi Chuan ; 44(3): 230-244, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-35307646

RESUMO

The abnormal expressions of minichromosome maintenance protein 2 (MCM2) are closely related to the development of various kinds of cancers. We aimed to explore the functions and potential molecular mechanisms of MCM2 gene in cholangiocarcinoma (CCA) cell lines (Huh28 and RBE). First, the cell counting kit-8 (CCK-8), plate clone formation, transwell and invasion assays showed that MCM2 promotes the proliferation, migration and invasion of CCA cells. Flow cytometry assays showed that MCM2 significantly promotes the cell cycle, and inhibits the apoptosis of CCA cells. Further, by analyzing the RNA sequencing data of cholangiocarcinoma, we found that MCM2 gene is significantly negatively correlated with p53 signaling pathway. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting (WB) assays confirmed that MCM2 in CCA cells significantly down-regulated the mRNA and protein expression levels of p53 and BAX, and up-regulated the mRNA and protein expression levels of BCL2 and CCND1. Flow cytometry, qRT-PCR and WB assays confirmed that MCM2 promotes CCA through p53 pathway. Finally, we found that MCM2 is up-regulated in CCA tissues compared to the matched non-tumor cholangiocarcinoma tissues, and the high expressions of MCM2 are significantly associated with the poor clinical outcomes of CCA patients. In conclusion, this study revealed that MCM2 promotes the development of CCA by reducing the p53 pathway, and its high expression levels predict poor prognosis in CCA patients. These results provide a theoretical basis for the development of new clinical diagnosis and treatment of cholangiocarcinoma in the future.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
3.
Clin Auton Res ; 32(1): 51-58, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35059875

RESUMO

PURPOSE: The etiology of constipation in Parkinson's disease is largely unknown. The aim of this study was to explore changes in regional neural activity and functional connections associated with constipation in a large cohort of individuals with Parkinson's disease. METHODS: We prospectively recruited 106 patients with Parkinson's disease with constipation and 73 patients with Parkinson's disease without constipation. We used resting-state functional magnetic resonance imaging for the first time to measure differences in regional neural activity and functional connections between the two patient groups. RESULTS: Patients with constipation showed significantly higher amplitude of low-frequency fluctuation than patients without constipation in the right dorsal pons extending into the cerebellum and in the right insula. The two types of patients also showed substantial differences in functional connections linking the superior temporal gyrus, particularly the right superior temporal gyrus, with multiple brain regions. CONCLUSION: Regional neural activity and functional connectivity in the brain differ substantially between patients with Parkinson's disease with or without constipation. These findings provide a foundation for understanding the pathophysiology of constipation in Parkinson's disease and for identifying therapeutic targets.


Assuntos
Doença de Parkinson , Encéfalo/diagnóstico por imagem , Constipação Intestinal/complicações , Constipação Intestinal/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Estudos Prospectivos
4.
Front Immunol ; 12: 720354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539656

RESUMO

Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.


Assuntos
Suscetibilidade a Doenças , Gastroenteropatias/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Adolescente , Adulto , Biomarcadores , Citocinas/metabolismo , Disbiose , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/metabolismo , Gastroenteropatias/terapia , Microbioma Gastrointestinal/imunologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/metabolismo , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunomodulação , Imunofenotipagem , Mediadores da Inflamação/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Transdução de Sinais , Transplante Homólogo/efeitos adversos , Adulto Jovem
5.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229053

RESUMO

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumonia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumonia/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
6.
Curr Med Sci ; 41(3): 443-453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34185250

RESUMO

We performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs. 71% vs. 16%, P<0.001) and lower leukemia-free survival (LFS) (46% vs. 21% vs. 70%, P<0.001) and overall survival (OS) (50% vs. 28% vs. 72%, P<0.001) than in group A, but there was no significant difference in non-relapse mortality (NRM) among three groups (14% vs. 12% vs. 8%, P=0.752). Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR (HR=2.392, 95% CI, 1.816-3.151, P<0.001), LFS (HR=1.964, 95% CI, 1.546-2.496, P<0.001) and OS (HR=1.731, 95% CI, 1.348-2.222, P<0.001). We also established a risk scoring system based on dynamic peri-HSCT MRD combined with remission status pre-HSCT and onset of chronic graft-versus-host disease (GVHD). This risk scoring system could better distinguish CIR (c=0.730) than that for pre-HSCT MRD (c=0.562), post-HSCT MRD (c=0.616) and pre- and post-MRD dynamics (c=0.648). Our results confirm the outcome predictive value of dynamic peri-HSCT MRD either alone or in combination with other variables for patients with T-ALL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasia Residual/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Citometria de Fluxo , Fator Estimulador de Colônias de Granulócitos/genética , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Recidiva , Linfócitos T/patologia , Adulto Jovem
7.
Front Oncol ; 11: 639502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718234

RESUMO

Objective: Haploidentical stem cell transplantation (haplo-SCT) has demonstrated encouraging results in younger patients. There is also an increasing need for haplo-SCT in older patients. However, the high risk of treatment-related mortality (TRM) in older patients is still a major concern. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-SCT in older patients. Method: This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia or MDS; (2) without MSD and MUD, and with HID available; and (3) age ≥55 years. The Bu/Flu/Cy/ATG regimen consisted of the following agents: Ara-C (2 g/m2/day, injected i.v.) on days-10 and-9; BU (9.6 mg/kg, injected i.v. in 12 doses) on days-8,-7, and-6; Flu (30 mg/m2/day, injected i.v.) from day-6 to day-2; Cy (1 g/m2/day, injected i.v.) on days-5 and-4; semustine (250 mg/m2, orally) on day-3 and antithymocyte globulin (ATG) [2.5 mg/kg/day, rabbit, SangStat (Lyon, France)] on days-5,-4,-3, and-2. The primary endpoint was 1-year TRM. Results: From April 1, 2018 to April 10, 2020, a total of 50 patients were enrolled. All patients achieved neutrophil engraftment with complete donor chimerism. The cumulative incidence of grade 2-4 aGVHD at day-100 was 22.0%. The cumulative incidences of CMV viremia and EBV viremia on day 100 were 68.0 and 20.0%, respectively. The cumulative incidence of TRM at 1-year was 23.3%. and the cumulative incidence of relapse (CIR) at 1 year after transplantation was 16.5%. The overall survival (OS) and leukemia-free survival (LFS) at 1 year were 63.5 and 60.2%, respectively. The outcomes were also comparable with patients who received Bu/Cy/ATG regimen using a propensity score matching method. Conclusions: In conclusion, this study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for older patients. The study was registered as a clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03412409.

8.
J Cancer Res Clin Oncol ; 147(1): 223-233, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32691153

RESUMO

BACKGROUND: This study was designed to detect patients with early NSCLC with tentatively using the stem signatures associated autoantibodies (AAbs), and to evaluate its latent values in the early diagnosis and precise prognosis prediction. METHODS: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 458 cases were enrolled (training set = 401; validation set = 57). TCGA databases were used to analyze the distinct expressions and prognostic values of related genes. The optimal cut-off values were 11.60 U/ml for P53, 4.90 U/ml for MAGEA1, 3.85 U/ml for SOX2, and 7.05U/ml for PGP9.5. RESULTS: We found that the stem signatures associated antibodies of MAGEA1, PGP9.5, SOX2, and TP53 exhibited high expressions in NSCLC, negatively correlating with the overall survival (OS) (P < 0.05). In the test groups, the diagnosis sensitivity of P53, PGP9.5, SOX2, and MAGEA1 reached to 21.5%, 39.0%, 50.3%, and 35.0%, respectively, and the specificity reached to 98.7%, 99.4%, 92.2%, and 97.4%. The four candidates' panel gave a sensitivity of 71.8% with a specificity of 89%. In the validation group, the detection of the four antibodies in early diagnosis of NSCLC also exhibited high specificity and sensitivity, further consolidating their potential application. CONCLUSIONS: The detection regarding stem signatures associated antibodies could be used as effective tools in early NSCLC diagnosis, but not for localized screening of cancers, and their abnormal expression was in accordance with poorer survival.


Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/patologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/patologia , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Autoanticorpos/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Taxa de Sobrevida
9.
J Dig Dis ; 22(1): 31-40, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33128287

RESUMO

OBJECTIVE: This study aimed to determine the risk factors and establish a risk score for post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE). METHODS: Altogether 299 and 62 cirrhotic patients receiving TIPS from January 2015 to March 2018 were divided into the derivation and validation cohorts, respectively. The data of the derivation cohort were analyzed for risk factors of post-TIPS OHE. A risk score was established from the derivation cohort and verified by the validation cohort. RESULTS: During a median follow-up of 112.6 weeks, 52 (17.4%) patients in the derivation cohort experienced post-TIPS OHE. Logistic regression showed that alcoholic cirrhosis (odds ratio [OR] 3.068, 95% confidence interval [CI] 1.423-6.613, P = 0.004), stent diameter of 10 mm (OR 12.046 [95% CI 2.308-62.862], P = 0.003), portal pressure gradient (PPG) decrement ≥60% (OR 3.548 [95% CI 1.741-7.230], P < 0.001), model for end-stage liver disease (MELD) score ≥10 (OR 2.695 [95% CI 1.203-6.035], P = 0.016), blood ammonia (OR 1.009 [95% CI 1.000-1.018], P = 0.043) and notable hydrothorax (OR 4.393 [95% CI 1.554-12.415], P = 0.005) were associated with an increased risk of post-TIPS OHE. The risk score reached a promising risk evaluation of post-TIPS OHE when verified by the validation cohort (sensitivity 71.4%, specificity 70.7%, accuracy 71.0%). CONCLUSIONS: Alcoholic cirrhosis and notable hydrothorax are independent risk factors for post-TIPS OHE in liver cirrhosis, together with the stent diameter of 10 mm, PPG decrement ≥60%, MELD score ≥10 and blood ammonia. The established risk score is reliable to identify high-risk individuals of developing post-TIPS OHE.


Assuntos
Encefalopatia Hepática , Cirrose Hepática , Derivação Portossistêmica Transjugular Intra-Hepática , Doença Hepática Terminal , Humanos , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
10.
J Cosmet Dermatol ; 20(5): 1374-1380, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33185943

RESUMO

BACKGROUND: Hypertrophic scar is a common complication in would healing process, and how to effectively prevent and treat it has been a hot and difficult research issue. Previous studies have showed that botulinum toxin type A (BTA) has effects on the prevention and treatment of hypertrophic scar, but little is known about the specific mechanisms. OBJECTIVE: This study aimed to explore the potential mechanisms of BTA on the inhibition of hypertrophic scar formation. METHODS: Hypertrophic scar-derived human fibroblasts were cultured and then treated with transforming growth factor-ß1 (TGF-ß1) and various concentrations of BTA. Cell proliferation and viability were measured by CellTiter 96® AQueous One Solution Cell Proliferation Assay and trypan blue staining, respectively. The total amount of collagen was examined using Sirius red staining. Collagen I and Collagen III in the culture supernatant were evaluated by enzyme-linked immunosorbent assay. Reverse transcription-quantitative polymerase chain reaction and Western blot analysis were performed to detect the transcription and translation levels. RESULTS: Our results revealed that BTA decreased the proliferation of hypertrophic scar-derived human fibroblasts. The mRNA and protein expression levels of alpha-smooth muscle actin, collagen I, and collagen III induced by TGF-ß1 were inhibited by BTA in a dose-dependent manner. BTA also inhibited the phosphorylation of Smad2/3 and ERK. CONCLUSION: BTA decreased the proliferation of fibroblasts and prevented overdeposition of ECM through the inhibition of the TGF-ß1/Smad and ERK pathways. The findings of this study provide new scientific reference for the prevention and treatment of hypertrophic scar.


Assuntos
Toxinas Botulínicas Tipo A , Cicatriz Hipertrófica , Toxinas Botulínicas Tipo A/farmacologia , Células Cultivadas , Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/prevenção & controle , Fibroblastos/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
11.
Transpl Infect Dis ; 23(3): e13544, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33326670

RESUMO

BACKGROUND: Human herpesvirus 6 (HHV-6) reactivation is relatively common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the incidence of HHV-6 reactivation and the clinical outcomes following unmanipulated haploidentical HSCT (haplo-HSCT) remain unknown. METHOD: We prospectively monitored blood HHV-6 DNA using real-time quantitative polymerase chain reaction weekly until day 100 post unmanipulated haplo-HSCT in patients with hematological malignancies. RESULTS: From November 2016 to March 2017, 102 patients (58 male and 44 female, median age 25(2-58) years old) were enrolled. Within 100 days post-transplantation, 27 patients (27/136, 19.9%) developed HHV-6 viremia with a median onset time of 14 (7-98) days. The cumulative incidence of HHV-6 reactivation on day 100 post-HSCT was 25.5 ± 4.3% in haplo-HSCT. The median HHV-6 copy number was 1.45 × 103 (5.48 × 102 -2.00 × 104 ) copies/ml. The HHV-6 viremia duration time was 7 days in 23 patients, 14 days in one patient and 21 days in one patient. In multivariate analysis, prior HHV-6 reactivation was an independent risk factor for grade 2-4 graft-versus-host disease (GVHD). But it did not influence the overall survival (OS)(HR 1.624, 95%CI 0.768-3.432, P = .204), disease-free survival (DFS) (HR 1.640, 95%CI 0.799-3.367, P = .177) and non-relapse mortality (NRM) (HR 1.644, 95%CI 0.670-4.038, P = .278). CONCLUSION: The reactivation of HHV-6 after unmanipulated haploidentical transplantation predicts the occurrence of grade 2-4 a-GVHD, but it may not influence the overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM).


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Infecções por Roseolovirus , Ativação Viral , Adulto Jovem
12.
Dose Response ; 18(2): 1559325820917829, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32704240

RESUMO

Colon cancer (CC) is considered one of the most common and lethal malignancies occurring both in male and female. Its widespread prevalence demonstrates the need for novel diagnostic and prognostic biomarkers for CC. Emerging evidence has shown that small nucleolar RNAs play critical roles in tumor development. In this study, we investigated the expression profile and functions of SNORD16 in CC. Our data showed that SNORD16, rather than its host gene (RPL4), was upregulated in CC cell lines. Compared to matched adjacent normal tissues, CC tissues showed higher SNORD16 expression levels, and no correlation was found between SNORD16 and RPL4. Patients with high SNORD16 expression levels had a worse prognosis, and multivariate analysis showed the high SNORD16 expression was an independent prognostic factor for CC. In vitro gain- and loss-of-function studies revealed that SNORD16 can promote cell growth, proliferation, migration, and invasion of CC cells by inhibiting apoptosis. These results suggested that SNORD16 has an oncogenic role in CC and might be a novel diagnostic and prognostic biomarker for CC.

13.
Medicine (Baltimore) ; 98(13): e14976, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921205

RESUMO

The aim of this study was to describe and assess the efficacy of a combination of multiple artery-first approaches (CMAFA) in pancreatoduodenectomy (PD) depending on the tumor location from an embryonic point of view.Between January 2011 and December 2016, seventy-nine consecutive patients with pancreatic head cancer (PHC) underwent PD with curative intent. Patients were classified into two groups according to the surgical procedure: CMAFA-PD group (n = 38) and conventional PD (Co-PD) group (n = 41). Clinicopathlogical variables and clinical outcomes were compared among the two groups.The CMAFA technique demonstrated an improved rate of R0 resection (89.5% vs. 70.7%, P = .038) and a higher median lymph node yield (24 vs.20, P = .034). The CMAFA-PD group was associated with reduced blood loss (450 vs. 600 ml, P = .049), lower rate of blood transfusion (23.7% vs. 46.3%, P = .035), and shorter length of hospital stay (19 vs. 26 days, P < .001). The rates of 90-day mortality, major morbidity, and readmission were comparable among the two groups.This study demonstrates that CMAFA is a feasible and efficient technique with acceptable perioperative and oncological outcomes in treating patients with PHC.


Assuntos
Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Excisão de Linfonodo/métodos , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Readmissão do Paciente/estatística & dados numéricos
14.
J Hematol Oncol ; 12(1): 31, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885244

RESUMO

INTRODUCTION: Myeloid-derived suppressor cells (MDSCs) are proposed to control graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the definition of human MDSCs has not yet reached consensus, and the mechanism of MDSCs to control GVHD remains unclear. METHODS: Immature myeloid cells (HLA-DR-/lowCD33+CD16-) were tested before and after granulocyte colony-stimulating factor (G-CSF) administration in healthy donor and isolated for suppression assays and co-culture with T cells in vitro. Isolated cells were infused in humanized mice for a xenogeneic model of acute GVHD. One hundred allo-HSCT recipients were enrolled prospectively to assess the role of HLA-DR-/lowCD33+CD16- cells in grafts on the occurrence of acute GVHD. RESULTS: In the present study, G-CSF mobilized HLA-DR-/lowCD33+CD16- cells with immunosuppressive properties in donor peripheral blood. These cells contained more interleukin-10+ and transforming growth factor-beta (TGF-ß)+ cells after G-CSF administration and inhibited the proliferation of autologous donor T cells in a TGF-ß-dependent manner. Meanwhile, these immature myeloid cells promoted regulatory T cell expansion and induced Th2 differentiation. Importantly, these cells prevented acute GVHD in a humanized mouse model. Moreover, clinical cohort results showed that the number of HLA-DR-/lowCD33+CD16- cells in the donor graft was the only independent risk factor inversely correlated with the incidence of grade II-IV acute GVHD in the recipients (HR 0.388, 95% CI 0.158-0.954, p = 0.039). CONCLUSION: HLA-DR-/lowCD33+CD16- cells represent functional MDSCs that may control acute GVHD in allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Fator Estimulador de Colônias de Granulócitos/metabolismo , Transplante de Células-Tronco Hematopoéticas/métodos , Células Supressoras Mieloides/metabolismo , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1442-1446, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295265

RESUMO

OBJECTIVE: To investigate the relationship between acute graft-versus-host disease and graft composition in patients with aplastic anemia(AA) after haploidentical hematopoietic stem cell transplantation. METHODS: Fifty-seven cases of AA after haploidentical hematopoietic stem cell transplantation were retrospectively analyzed. All the patients were divided into 2 groups according to whether presence or absence grade Ⅱ-Ⅳ aGVHD, the relationship between aGVHD and graft composition was analyzed by comparing the differences of graft components between the 2 groups. RESULTS: Fourteen out of 57 patients had grade Ⅱ-Ⅳ aGVHD and the other 43 did not have grade Ⅱ-Ⅳ aGVHD. The mononuclear cells, CD3+, CD4+, CD8+, NK cells, NKT cells, B cells and Treg cells were not significantly different between the 2 groups (P>0.05), the CD34+ cell count in the patients with grade Ⅱ-Ⅳ aGVHD was 3.85(1.73-10.61)×106/kg, which was significantly lower than that without grade Ⅱ-ⅣaGVHD: 6.31(2.98-19.35)×106/kg (P<0.05). CONCLUSIONS: The incidence of grade Ⅱ-Ⅳ aGVHD may be related with CD34+ cell count in AA after haploidentical hematopoietic stem cell transplantation..


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Humanos , Estudos Retrospectivos , Linfócitos T Reguladores
16.
Cell Physiol Biochem ; 49(5): 1933-1942, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30235453

RESUMO

BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. METHODS: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. RESULTS: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/ß-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/ß-catenin signaling pathway as detected by an increased level of ß-catenin and phosphorylation of GSK-3ß, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. CONCLUSION: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Antagomirs/metabolismo , Apoptose , Sequência de Bases , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosforilação , Proteínas Proto-Oncogênicas c-myc/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Via de Sinalização Wnt , beta Catenina/metabolismo
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1524-1527, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070137

RESUMO

OBJECTIVE: To analyze the therapeutic efficacy of haploidentical-hematopoietic stem cell transplantation (hi-HSCT) for patients with juvenile myelomonocytic leukemia (JMML). METHODS: The engraftment of hematopoietic stem cells, incidence of graft versus host disease (GVHD), infection, relapse, and survival of 6 JMML patients received hi-HSCT were retrospectively analyzed. RESULTS: Six (6 males) JMML patients received hi-HSCT from haplo-HLA-matched related donors. The results showed that the hematopoictic stem cells in all 6 patients were grafted successfully. Two cases of JMML died of pulmenary infections, other 4 cases survive without disease. Acute GVHD occurred in 3 patients and chronic GVHD occurred in 1 patients. The overall survival, disease free survival and relapse rates were 66.7%, 66.7%, 0%, respectively. CONCLUSION: The hi-HSCT is an effective method for treatment of patients with JMML, but there also is a serial problems to be resolved.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Juvenil/terapia , Criança , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro , Humanos , Masculino , Transplante Homólogo
18.
Int J Hematol ; 106(6): 820-831, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28825215

RESUMO

In the present study, we sought to analyze the risk factors following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in children with high-risk acute leukemia. We retrospectively reviewed data from 73 children with high-risk leukemia. Univariate and multivariate analyses were performed to evaluate relationships between variables and patient outcomes. The mean time for neutrophil engraftment was significantly shorter in children given a graft with a higher number of nucleated cells (>10.13 × 108/kg vs ≤10.13 × 108/kg: 13.79 ± 2.73 vs 17.71 ± 3.90 days, P < 0.001) and in younger children (≤10 years vs >10 years: 14.21 ± 3.12 vs 17.71 ± 3.90 days, P < 0.001). Time to platelet engraftment was clearly shorter in children given a graft with higher number of nucleated cells (>10.13 × 108/kg vs ≤10.13 × 108/kg: 12.12 ± 8.62 vs 32.1 ± 24.83 days, P < 0.028). Overall survival was 64.6 ± 9.1%, 41.1 ± 10.1%, and 81.6 ± 9.6%, respectively, in children with HR-ALL in CR1, ALL in CR2-4, and AML (P = 0.012). The number of total nucleated cells was significantly associated with transplant-related mortality (TRM). We suggest that outcomes of haplo-HSCT may be improved by increased infusion of nucleated cells.


Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Fatores Etários , Aloenxertos , Criança , Pré-Escolar , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Masculino , Fatores de Risco , Doadores não Relacionados
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(4): 1151-1157, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28823285

RESUMO

OBJECTIVE: To analyse the efficacy and safety of co-transplantation of umbilical cord mesenchymal stem cell(UC-MSC) with haploidentical hematopoietic stem cell transplantation(hi-HSCT) in children with hematologic malignancy. METHODS: The clinical data of 47 children undergoing hi-HSCT were retrospectively analyzed from November 2003 to November 2014, among them 34 patients received UC-MSC from October 2011 to November 2014, and another 13 patients without UC-MSC from November 2003 to September 2011. The median follow-up time was 20(0.5-67) months. RESULTS: No adverse events were observed after the UC-MSC transplantation. The engraftment rate, the median neutrophils engraftment time and platelet engraftment time all were not significantly different between hi-HSCT and hi-HSCT+UC-MSCT(P>0.05). The three-years cumulative overall survival (70.6% vs 23.1%),(P=0.004), three-years cumulative disease-free survival(52.9% vs 0) (P=0), and early cytomegalovirus (CMV) viremia (91.2% vs 38.5%) (P=0) in UC-MSC+hi-HSCT group were statistically significantly higher than that in the conventional hi-HSCT group. The morbidity of aGVHD (44.1% vs 92.3%) (P=0.003), I-II aGVHD (26.5% vs 61.5%) (P=0.041) and transplantation-related mortality (11.8% vs 46.2%) (P=0.017) in UC-MSC+hi-HSCT group was statistically significantly lower than that in hi-HSCT group, however, the morbidity of III-IV aGVHD (17.6% vs 30.8%), cGVHD (26.5% vs 30.8%), HC (35.3% vs 7.7%), pulmonary infection (52.9% vs 46.2%) and relapse rate (32.4% vs 53.8%) were not statistically significantly different (P>0.05) between the 2 groups. CONCLUSION: The application of umbilical cord mesenchymal stem cell in children undergoing hi-HSCT is safe, the UC-MSC can improve the overall survival, disease-free survival and reduce transplantation-related mortality. UC-MSC can reduce the morbidity of aGVHD, but increase the early infection of CMV, however it is nothing for the pulmonary infection and relapse in the children after hi-HSCT.


Assuntos
Células-Tronco Mesenquimais , Recidiva Local de Neoplasia , Criança , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Mesenquimais , Estudos Retrospectivos , Cordão Umbilical
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(4): 1158-1164, 2017 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-28823286

RESUMO

OBJECTIVE: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation(hi-HSCT) combined with bone-marrow derived mesenchymal stem cell (BM-MSC) tranfusion for treatment of children with severe apastic anemia(SAA). METHODS: The clinical data of 25 children with SAA undergoing hi-HSCT and BM-MSC tranfusion were retrospectively analyzed from August 2014 to July 2016. RESULTS: neutrophil engraftment was achieved in all 25(100%) children, with the median time 12(11-22) days. The median time of platelet engraftment was 21(11-130) days in 23(92%) children. Acute graft-versus-host disease(aGVHD) was observed in 16(64%) cases, including 11 case of grade I and 5 cases of aGVHD grade II-IV, and one of them died of grade IV of skin, gut and liver at day 115; 5 cases of chronic GVHD were found, all of them were limited cGVHD. Cytomegalovirus (CMV) viremia was observed in 23(92%) cases, but no CMV disease was developed after therapy. 3 cases of post-transplant lymphoroliferative disease with 23 EBV viremia positive occurred, all of them were cured after rituximab. Hemorrhagic cystitis appeared in 9 cases with only one case of grade III, 22 children suffered from infection, involving 10 cases in lung and 4 cases in liver, 1 patient was diagnosed as Guillain-Barre syndrome. Autoimmune hemolytic anemia was recorded in 1 patient, 22 children survived during a median following-up time of 14(3-27) months. CONCLUSION: The hi-HSCT combined with BM-MSC transfusion for treatment of children with SAA has been confirmed to be safe and feasible.


Assuntos
Anemia Aplástica , Medula Óssea , Células-Tronco Mesenquimais , Criança , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Mesenquimais , Estudos Retrospectivos
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