RESUMEN
Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Proteínas de Complejo Poro Nuclear , Trasplante Homólogo , Humanos , Masculino , Femenino , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Persona de Mediana Edad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Adolescente , Estudios Retrospectivos , Adulto Joven , Proteínas de Complejo Poro Nuclear/genética , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión a Poli-ADP-Ribosa/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Oncogénicas/genética , Translocación GenéticaRESUMEN
Objective: To analyze the effect and prognosis of infant kidney transplantation. Methods: Clinical data of 37 cases of infant kidney transplantation under 3 years old in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from June 1, 2017 to July 31, 2022 were retrospectively collected. These 37 cases included 31 primary kidney transplantation and 6 secondary kidney transplantation. Kaplan-Meier method was used to draw the survival curve of the transplanted kidney and the recipient, and the prognosis and complications were analyzed. Median follow-up was 18 months (range: 6-66 months). Results: The recipients were 20 males and 17 females, with a median age of 16 months (range: 2 months, 26 days to 36 months) and a median weight of 8 kg (range: 3.2 to 14.0 kg). The youngest child was only 2 months, 26 days old, and weighed only 3.2 kg. The most common primary disease of recipients was congenital nephrotic syndrome (13 cases, 41.9%). Intra-abdominal transplantation occurred in 19 cases (51.3%) and intra-iliac fossa transplantation occurred in the remaining 18 cases (48.6%). Postoperative renal function recovery was delayed in 7 cases (18.9%), and thrombosis caused renal function loss in 5 cases (13.5%), of which 4 cases received second renal transplantation and were successful. During the follow-up period, there were 11 cases of acute rejection (29.7%) and 6 cases of CMV pneumonia (16.2%). The estimated glomerular filtration rate 1 year after transplantation was higher than that 1 month after surgery [(101.9±22.1) vs (71.1±25.6) ml/(min·1.73m2), P<0.001], and remained constant 2 years after transplantation. Both the 1-year and 2-year survival rates of the transplanted kidney were 85.3%, and both the 1-year and 2-year survival rates of the recipients were 96.8%. Conclusion: Although the implementation of infant kidney transplantation is difficult, it can still achieve relatively satisfactory efficacy and prognosis.
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Trasplante de Riñón , Preescolar , Femenino , Humanos , Lactante , Masculino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Riñón , Pronóstico , Estudios RetrospectivosRESUMEN
Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1â¶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.
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Antineoplásicos , Tumores del Estroma Gastrointestinal , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , China , Femenino , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Recurrencia Local de Neoplasia , Pronóstico , Proteínas Proto-Oncogénicas c-kit/genética , Pirazoles , Pirroles , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Estudios Retrospectivos , TriazinasRESUMEN
Objective: Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods: A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results: A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ(2)=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups (P=0.233). Univariate analysis revealed that mitotic count (P=0.002), Ki-67 proliferation index (P<0.001) and modified NIH grade (P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion: Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.
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Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/genética , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/genética , Exones , Femenino , Neoplasias Gastrointestinales/mortalidad , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/mortalidad , Tumores del Estroma Gastrointestinal/terapia , Humanos , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. METHODS: A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. RESULTS: In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. CONCLUSIONS: Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/diagnóstico , Quimiocina CCL2 , China , Disfunción Cognitiva/diagnóstico , Femenino , Humanos , Masculino , Pruebas NeuropsicológicasRESUMEN
Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: â After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. â¡Univariate analysis showed that patients with grade â ¢-â £ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. â¢Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade â ¢-â £ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Estudios Retrospectivos , Hermanos , Acondicionamiento Pretrasplante , Trasplante HomólogoRESUMEN
BACKGROUND: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a severe allergic condition in which wheat ingestion together followed by physical exercise induces anaphylaxis. For patients with WDEIA, omega-5 gliadin is considered to be one of the major allergens. AIM: To analyse the clinical features and allergen spectrum of WDEIA and to investigate the relationship between WDEIA and serum levels of platelet-activating factor (PAF), interleukin (IL)-9 and IL-33. METHODS: Medical histories and conditions of WDEIA cases were collected and summarized, with allergen tests of wheat proteins measured at the same visit. Of the 33 patients enrolled, 13 also had serum levels of PAF, IL-9 and IL-33 measured. The healthy control (HC) group consisted of 13 healthy individuals, who also underwent both the wheat-protein allergen tests and the inflammatory-mediator tests. RESULTS: All patients experienced severe allergic reaction during exercise after wheat ingestion. Manifestations of WDEIA included facial oedema, generalized urticaria and respiratory symptoms. Unconsciousness was also observed in 21 cases. In the patient group, 57.6% were confirmed as hypersensitive to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), while 54.5% were allergic to omega-5 gliadin. PAF concentration was significantly higher in patients with WDEIA compared with HCs, whereas there was no significant difference in IL-9 or IL-33 between the two groups. CONCLUSIONS: WDEIA is a rare type of anaphylaxis. GAPDH and omega-5 gliadin may be the most common allergy-causing wheat proteins for Chinese people. PAF may be associated with the onset and development of WDEIA.
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Anafilaxia/etiología , Ejercicio Físico/fisiología , Gliadina/inmunología , Triticum/efectos adversos , Hipersensibilidad al Trigo/etnología , Adolescente , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Triticum/inmunología , Inconsciencia/etiología , Hipersensibilidad al Trigo/inmunologíaRESUMEN
OBJECTIVE: To compare the effects of thoracic epidural administration of lidocaine on hemodynamic and arousal responses of double lumen tracheal intubation during induction of anesthesia. METHODS: In the study, 40 patients with American Society of Anesthesiologists (ASA) physical statuses I-II, aged 19-66 years, scheduled for elective thoracic surgeries under general anesthesia requiring orotracheal intubation were allocated to either the double-lumen endobronchial intubation (T group) or double-lumen endobronchial intubation after epidural administration of lidocaine (E group). After an intravenous anesthetic induction, the orotracheal double-lumen intubation was performed using a Macintosh direct laryngoscopy (MDLS), respectively. Invasive blood pressure (BP), heart rate (HR) and bispectral index (BIS) were recorded before and after anesthetic induction, immediately after intubation and 5 minutes after intubation with 1-minute interval and the intubation time also noted. The rate pressure product (RPP) was calculated. RESULTS: After anesthetic induction, BP and RPP in the two groups decreased significantly compared with their preinduction values. In comparison with their postinduction values, the orotracheal intubation in the two groups caused significant increases in BPs, HRs and RPP. In comparison with their preinduction values, BPs decreased significantly in E group, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) increased significantly and lasted for 1 min in T group. The HRs of both groups after intubation were significantly higher than their baseline values , and increased in HR and lasted for 1 min and 4 min in E group and T group, respectively. SBP, DBP, MAP, HR and RPP after intubation in T group were significantly higher than those of E group during the observation period. The values of BIS were similar between both the groups. In T group, the incidences of SBP percent increased>30% of the baseline value and RPP more than 22 000 were significantly higher than in E group. None of the patients in group E had SBP more than 130% of the baseline value and RPP more than 22 000. CONCLUSION: During double-lumen endobronchial intubation, epidural administration of lidocaine can provide less hemodynamic response and similar arousal response.
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Intubación Intratraqueal , Laringoscopios , Adulto , Anciano , Nivel de Alerta , Presión Sanguínea , Frecuencia Cardíaca , Hemodinámica , Humanos , Lidocaína , Persona de Mediana Edad , Adulto JovenRESUMEN
Objective: To evaluate the outcomes of human leukocyte antigen (HLA) matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) for adult acute myeloid leukemia (AML) in a single center. Methods: Consecutive adult AML who received MUD-HSCT in our center from January 2008 to April 2017 were studied retrospectively, comparing with patients undergoing matched sibling donor (MSD) -HSCT in the same period. The rates of overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) , engraftment, acute and chronic graft-versus-host disease (aGVHD and cGVHD) were analyzed. Results: A total of 247 consecutive cases were enrolled, including 46 patients with MUD-HSCT and 201 with MSD-HSCT. All the patients experienced neutrophil engraftment except for one patient who died early in the MSD group, but the median day of engraftment was longer in the MUD group (15.0 vs 14.0, P=0.017) . The accumulative engraftment rate of platelet was comparable between the two groups (93.5%vs 98.0%, P=0.128) . The accumulative incidences of aGVHD (50.0%vs 46.3%, P=0.421) and cGVHD (37.8%vs 43.0%, P=0.581) were not statistically different between the two groups. Compared with the MSD group, the accumulative NRM rate at+36 months after transplantation was significantly higher in the MUD group (22.0%vs 10.4%, P=0.049) , while the relapse rate was not statistical difference (20.5 vs 28.3%, P=0.189) . Both the 3-year OS (61.6%vs 63.3%, P=0.867) and DFS (57.5%vs 61.6%, P=0.760) were comparable between the two groups. Four independent risk factors were confirmed by the multivariate analysis: patient age ≥45 years old, CR2 or NR before transplantation, a history of extramedullary infiltration and the occurrence of grade â ¢-â £ aGVHD. No statistical differences were demonstrated in the survival rate between MUD-and MSD-HSCT in different subgroups. Conclusions: The outcomes, such as GVHD, relapse, OS and DFS, were comparable between MUD-and MSD-HSCT for adult AML, but higher incidence of NRM and longer time to neutrophil engraftment in the MUD group. MUD-HSCT is practical and feasible for adult AML who are lack of MSD.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Antígenos HLA , Humanos , Leucemia Mieloide Aguda/terapia , Persona de Mediana Edad , Estudios Retrospectivos , Hermanos , Donante no EmparentadoRESUMEN
OBJECTIVE: This study aimed at exploring the role and mechanism of Krüppel-like factor 5 (KLF5) in the migration, invasion, epithelial-mesenchymal transition (EMT) induction and proliferation in laryngeal cancer human epithelial type 2 (Hep-2) cells, and to provide a new sight for the treatment of laryngeal carcinoma. MATERIALS AND METHODS: Hep-2 cells were randomly divided into three groups: control group (Control), KLF5 siRNA group (siKLF5) and control-siRNA group (NC). The effects of KLF5 inhibition on cell proliferation and apoptosis were assessed by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometer, respectively. Wound healing assay and transwell invasion experiments were used to determine cell migration and invasion. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot were used to compare the levels of KLF5, EMT-related genes E-cadherin, N-cadherin, Vimentin and Zinc finger transcription factors (Snail, Slug) expressions. The levels of nuclear transcription factor-κB (NF-κB-p65) and IκBα were also detected by Western blot. RESULTS: Compared with the Control group, the proliferation rate of Hep-2 cells in the siKLF5 group was significantly decreased while the apoptosis rate was increased (p<0.05). Meanwhile, the migration and invasion ability of Hep-2 cells were markedly decreased (p<0.05). E-cadherin protein expression was up-regulated while Vimentin, N-cadherin, Snail, and Slug protein expression levels were downregulated in siKLF5 group (p<0.05). Silencing KLF5 could inhibit the expression of NF-κB phosphorylation at p65 and the IκBα degradation (p<0.05). CONCLUSIONS: These results revealed that silencing KLF5 expression reduced the proliferation, migration and invasion and EMT abilities by inhibiting the NF-κB pathway in Hep-2 cells. Our results suggest that KLF5 may be a potential therapeutic target in laryngeal carcinoma.
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Transición Epitelial-Mesenquimal , Factores de Transcripción de Tipo Kruppel/metabolismo , FN-kappa B/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Factores de Transcripción de Tipo Kruppel/antagonistas & inhibidores , Factores de Transcripción de Tipo Kruppel/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Inhibidor NF-kappaB alfa/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Factores de Transcripción de la Familia Snail/metabolismo , Factor de Transcripción ReIA/metabolismo , Vimentina/metabolismoRESUMEN
Objective: To analyze risk factors and drug resistance of community-onset methicillin-resistant staphylococcus aureus (CO-MRSA) infection through the investigation of patients infected with CO-MRSA. Methods: The clinical data of 97 cases infected with community-onset staphylococcus aureus (COSA) was collected in this hospital from July 2016 to June 2017. Epidemiological survey method and the variables were determined according to expert consultation, literature and practical work experience. Results: Among 97 patients infected with COSA, the diagnosis rate of CO-MRSA was 21.65%(21/97). The drug sensitivity results showed that: CO-MRSA was high resistant to erythromycin, tetracycline and clindamycin, and the drug resistance rate exceeded 50%. Multiple variables were analyzed by Logistic regression. The usage of antimicrobial agents in the past three months and the history of hospitalization within one year were the independent risk factors. The MRSA infection rate was 57.89%(11/19) of the persons who had taken antibacterial agents in the recent three months.The MRSA infection rate was 48.28%(14/29) of the persons who had been hospitalized in the past one year. OR value of two risk factors was respectively 10.006(95%CI: 2.200-45.519, P=0.030) and 11.519(95%CI: 2.405-55.177, P=0.002). Conclusions: Most COSA is sensitive to methicillin, but CO-MRSA is multidrug resistant and has more risk factors. The clinicians should reasonably use the antibacterial agents according to the drug sensitivity in order to prevent the occurrence of multidrug resistant MRSA.
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Farmacorresistencia Bacteriana , Antibacterianos , Infecciones Comunitarias Adquiridas , Humanos , Meticilina , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the role of miR-451a in the migration and invasion of non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: Quantitative Real time-polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the levels of miR-451a and activating transcription factor 2 (ATF2) in NSCLC. Transwell assay was employed to analyze the migratory and invasive abilities in NSCLC cells. Dual-luciferase reporter assay was applied to confirm the binding condition of miR-451 and its target gene in NSCLC cells. RESULTS: MiR-451a was downregulated in NSCLC tissues and lung cancer cell lines A549 and NCI-H460, while ATF2 was upregulated. The mRNA level of miR-451a was negatively correlated to ATF2. Additionally, miR-451a regulated cell migration and invasion through targeting ATF2. Furthermore, ATF2 could reverse the inhibitory migration and invasion of A549 cells induced by miR-451a. CONCLUSIONS: MiR-451a inhibits the migratory and invasive abilities of NSCLC cells through ATF2 regulation. The newly identified miR-451a/ATF2 axis provides a novel insight into the pathogenesis ofNSCLC.
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Factor de Transcripción Activador 2/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/biosíntesis , Células A549 , Factor de Transcripción Activador 2/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Movimiento Celular/fisiología , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/genética , Invasividad Neoplásica/genética , Invasividad Neoplásica/patologíaRESUMEN
OBJECTIVE: To explore the expression and function of insulin-like growth factor II (IGFII) mRNA binding protein (IMP3) in the Triple Negative Breast Cancer (TNBC). MATERIALS AND METHODS: According to previously reported gene expression array, we found that IMP3 had significantly higher expression in the CD44+CD24-ESA+ cell cluster, tumor initiating cell or cancer stem cell (CSCs), compared to other tumor cells. Based on the GEO database (GEO accession No. GSE6883), we detected the mRNA levels of IMP 1,2 and 3 by quantitative polymerase chain reaction (q-PCR) in CD44+CD24-ESA+ cell cluster and other breast tumor cell clusters. Besides, we measured IMP3 expression in microsphere of breast cancer, which exerted more significant tumor stem cell properties. The effects of IMP3 on breast cancer cell stem cell properties were studied by RNA interference and overexpression approaches in vitro. Furthermore, we predicted and identified microRNA, which could target and regulate IMP3 from bioinformatics analysis, and verified the interaction by luciferase assays and rescue experiments. RESULTS: Previously reported data showed that IMP3 expression was significantly upregulated in CD44+CD24-ESA+ cell cluster from breast cancer tissues. Besides, we found IMP3 had higher expression in mesenchymal cells rather than epithelial cells, which was also significantly elevated in SUM159 and T49D cell lines cultured as microsphere rather than adherent cells or differentiated cells. CD44+CD24-ESA+ cell cluster proportion was significantly decreased after silencing IMP3 in SUM1315, and its ability to develop into microsphere was significantly inhibited. By re-expressing IMP3 in SUM315, we restored the self-renewal capacity and tumorigenesis potential of SUM315. Through relative predicting website, we found several miRNAs which could regulate IMP3. miR-34a with highest score was chosen for further analysis. Mimicking miR-34a significantly downregulated IMP3 expression and inhibited its ability to develop into microsphere, while overexpressing IMP3 could rescue this process. CONCLUSIONS: IMP3 plays a vital role in maintaining stem cell properties of breast cancer cells, which could be regulated by mir-34a.
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Proliferación Celular , Autorrenovación de las Células , MicroARNs/metabolismo , Células Madre Neoplásicas/metabolismo , Proteínas de Unión al ARN/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Animales , Línea Celular Tumoral , Bases de Datos Genéticas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , MicroARNs/genética , Células Madre Neoplásicas/patología , Fenotipo , Proteínas de Unión al ARN/genética , Transducción de Señal , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Objective: To investigate the clinical significance of tumor associated macrophages (TAM) in multiple myeloma (MM) and the relationship with angiogenesis and immunosuppression. Methods: Seventy cases of MM patients diagnosed from August 2015 to June 2017 were enrolled in the study as experimental group, 20 cases of benign hematological diseases (13 with iron deficiency anemia and 7 with megaloblastic anemia) patients as control group. Immunohistochemical method was used to detect the expression of CD163, CD34 and VEGF in bone marrow samples, and flow cytometry was used to detect the proportion of regulatory T cell (Treg cells), ELISA was used to detect the level of IL-10, and the clinical features were analyzed. Results: â Among the 70 patients, there were 31 males and 39 females with a median age of 65 (50~78) years old. TAM infiltration density, microvascular density (MVD), VEGF expression level, Treg ratio and IL-10 level in bone marrow samples of 70 MM patients were significantly higher than those of benign hematological diseases (P<0.05). â¡In the MM group, the above indexes of the patients with disease stabilized (15 cases) were lower than those of the newly diagnosed group (35 cases) and the relapse refractory group (20 cases) (P<0.05), those of relapse refractory group were higher than those of newly diagnosed group (P>0.05). â¢Of the 35 newly diagnosed MM patients, 27 completed 4 courses of treatment. In the effective group (15 cases), the TAM infiltration density after treatment was significantly lower than that before treatment, the difference was statistically significant[(20.20±7.66) vs (28.87±11.97), t=2.362, P=0.025]; while in the ineffective group of 12 cases, the difference of the TAM infiltration density before and after treatment was not statistically significant[(42.00±13.76) vs (48.25±13.59), t=1.119, P=0.275]. â£TAM infiltration density in the effective group after bortezomib treatment (21 cases) were lower than those in the non-bortezomib treatment group (18 cases)[(16.52 ±4.26) vs (19.27 ±5.82), t=1.662, P=0.170]. â¤The TAM infiltration density in MM patients was positively correlated with MVD, VEGF expression level, Treg cell ratio and IL-10 level (P<0.001). Conclusion: The infiltration of TAM in the microenvironment of MM, which may promoting angiogenesis and inhibiting immune response, is related to the occurrence, development, therapeutic effect and drug resistance of MM.
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Mieloma Múltiple , Anciano , Femenino , Humanos , Macrófagos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neovascularización PatológicaRESUMEN
Objective: To detect the expression of B cell transposition gene 3(BTG3) in pancreatic ductal adenocarcinoma(PDAC), and explore its relationship with postoperative recurrence and metastasis of tumor. Methods: Six self-paired frozen PDAC specimens and 3 normal pancreatic tissues from the Second Hospital of Jiaxing Affiliated to Jiaxing University were collected and the expression of BTG3 was detected by qPCR. Ten normal pancreatic tissues and 52 cases of PDAC tumor and paracarcinomatous tissues from the Second Hospital of Jiaxing Affiliated to Jiaxing University were collected from June 2009 to December 2016. The expression of BTG3 and relationship among BTG3 and clinicopathological characteristics of PDAC and patients' prognosis were detected and analyzed using immunohistochemistry.χ(2) test, Kaplan-Meier method and Cox regression model were used to analyzed the data. Results: The results of qPCR showed that expression level of BTG3 in PDAC (0.63±0.17) was lower significantly than that in paracarcinomatous (0.96±0.04) and normal tissues (1.00)(t=4.673, 5.502; both P<0.05). Immunohistochemistrv showed that BTG3 mainly expressed in the cytoplasm.The high expression rate of BTG3 in PDAC tumor tissues was 25.0%(13/52), which was remarkably lower than that in paracarcinomatous tissues(65.4%) and normal liver tissues(7/10)(χ(2)=17.120 and 5.849, both P<0.05). The low expression of BTG3 in PDAC was correlated with primary tumor, and TNM stage(χ(2)=7.704, P=0.006; U=154.000, P=0.018, respectively). Survival analysis showed that disease free survival rate of patients with low expression of BTG3 was significantly less than that with high expression(χ(2)=192.493, P<0.01). The Cox multivariate analysis demonstrated that low expression of BTG3 was independent risk factors for disease free survival in patients with PDAC after a curative resection(RR=3.366, 95%CI: 1.040-10.889, P=0.043). Conclusion: BTG3 may be involved in the occurence and development of tumor, and its low expression may be associated with poor prognosis in patients with PDAC.
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Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Proteínas/metabolismo , Linfocitos B , Carcinoma Ductal Pancreático/patología , Proteínas de Ciclo Celular , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Recurrencia Local de Neoplasia , Páncreas , Neoplasias Pancreáticas/patología , Pronóstico , Neoplasias PancreáticasRESUMEN
Objective: To investigate the mechanism of brain-derived neurotrophic factor (BDNF) promoting induced pluripotent stem cells (iPSCs) to differentiate into neural stem cells (NSCs) via Wnt/ß-catenin and extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK) signal pathways. Methods: iPSCs were cultured and identified. The iPSCs were induced to differentiate into NSCs by BDNF and retinoic acid (RA). Nestin was detected by immunofluorescence and flow cytometry after iPSCs differentiated. The technique of small interfering RNA (siRNA) was used to silence the gene expression of ß-catenin and ERK, and iPSCs were divided into control group, BDNF group (adding 10 µg/L BDNF), siRNA-ERK/BDNF group (transfected with siRNA-ERK and adding 10 µg/L BDNF) and siRNA-ß-catenin/BDNF group (transfected with siRNA-ß-catenin and adding 10 µg/L BDNF). Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expression of key elements of Wnt/ß-catenin and ERK/MAPK signaling pathways, included ß-catenin, ERK1/2, c-fos, c-jun, and c-myc. The least significant difference test was used when data were compared between groups. Results: The immunofluorescence showed that iPSCs expressed octamer-binding transcription factor-4 (Oct4), SRY-related HMG box protein-2 (Sox2) and Nanog genes. The flow cytometry showed that Nestin-positive cells were 78.7% for BDNF and 43.5% for RA, and it was only 7.8% for routine medium. Compared with those in the control group, the mRNA expression of ß-catenin, ERK1/2, c-fos, c-jun, and c-myc in the BDNF group were upregulated significantly (t=2.80, 2.318, 2.255, 1.799, 1.582, 1.663, all P<0.05), and the same results were acquired with the protein expression (t=2.805, 2.318, 2.255, 1.799, 1.582, 1.663, all P<0.050). Compared with those in BDNF group, the mRNA and protein expression of ERK1/2 in siRNA-ERK/BDNF group down-regulated obviously (t=1.917, 2.042, 1.673, 1.540, all P<0.05), and the mRNA and protein expression of c-fos and c-jun were down-regulated (t=1.022, 0.907, 0.848, 0.801, all P<0.05). However, the mRNA and protein expression of ß-catenin and c-myc were not suppressed by siRNA-ERK (t=0.216, 0.185, 0.097, 0.112, all P>0.05). In siRNA-ß-catenin/BDNF group, the mRNA and protein expression of ß-catenin and c-myc was obviously down-regulated when compared with those in BDNF group (t=3.104, 2.774, 2.235, 1.911, all P<0.05), and expression of ERK1/2, c-fos and c-jun were down-regulated too (t=0.776-1.192, all P<0.05). Conclusion: BDNF promotes the differentiation of iPSCs by activating Wnt/ß-catenin and ERK/MAPK signal pathway, there should be cross-talk between the two signal pathways, and c-fos and c-jun may be common nuclear transcription factors.
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Factor Neurotrófico Derivado del Encéfalo/fisiología , Diferenciación Celular , Células Madre Pluripotentes Inducidas , Células-Madre Neurales , beta Catenina/fisiología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , ARN Interferente Pequeño , Transducción de Señal , Vía de Señalización WntRESUMEN
Objective: To explore the lipid accumulation product (LAP) formula for Beijing adults and to investigate the relationship between lipid accumulation product and hypertension, as well as diabetes. Methods: A cross-sectional study with a representative sample of 19 606 residents in Beijing aged 18-79 years was conducted in 2011. The sex-specific hypothetical minimum waist circumference (WC) was calculated in order to obtain the more applicable LAP formula. Multivariate logistic regression was used to analyze the associations of LAP, combination of LAP and body mass index (BMI) with hypertension and diabetes. Results: The LAP formula for Beijing adults was established as follows: LAP (male)= (WC-61.3) × TG, and LAP (female)= (WC-55.6) × TG. There was an obvious trend of increased risk of hypertension and diabetes with an increment in the tertiles of the LAP both in men and women. The OR (95%CI) for hypertension in the group with highest tertile LAP was 3.62 (3.11-4.22) in men, and 5.79 (4.84-6.93) in women, compared with the lowest tertile group, respectively; and the corresponding OR for diabetes was 3.47 (2.73-4.41) in men, and 4.10 (2.90-5.80) in women, respectively. Compared with the lowest tertile of LAP and normal BMI group, the OR (95%CI) for hypertension in the highest tertile of LAP and obesity group was 6.79 (5.50-8.37) in men, and 9.75 (7.76-12.25) in women, respectively; while the corresponding value for diabetes was 3.97 (2.87-5.49) in men, and 4.13 (2.78-6.14) in women, respectively. Conclusion: The elevated level of LAP was associated with an increased risk of hypertension and diabetes among Beijing adults. LAP could be an important predictor for hypertension and diabetes.
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Diabetes Mellitus/epidemiología , Hipertensión/epidemiología , Producto de la Acumulación de Lípidos , Metabolismo de los Lípidos , Adolescente , Adulto , Anciano , Beijing/epidemiología , Índice de Masa Corporal , Tamaño Corporal , Estudios Transversales , Diabetes Mellitus/sangre , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Hipertensión/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/epidemiología , Circunferencia de la CinturaRESUMEN
Metastasis of the cervical lymph nodes frequently leads to poor survival of patients with oral squamous cell carcinoma (OSCC). The underlying mechanisms of lymph node metastasis are unclear. Wingless-type MMTV integration site family, member 5B (WNT5B), one component of the WNT signal pathway, was markedly up-regulated in OSCC sublines with high potential of lymphatic metastasis compared to that in OSCC cells with low nodal metastasis. Increased WNT5B mRNA was demonstrated in human OSCC tissues in comparison with adjacent non-tumorous tissues. Interestingly, the high level of WNT5B protein in serum was associated with lymph node metastasis in OSCC patients. Knockdown of WNT5B expression in OSCC sublines did not affect tumour growth but impaired lymph node metastasis and tumour lymphangiogenesis of orthotopic transplantation. Conditioned medium from WNT5B knockdown cells reduced the tube formation of lymphatic endothelial cells (LECs). In contrast, recombinant WNT5B enhanced the tube formation, permeability and migration of LECs. In LECs stained with phalloidin, the morphology of those treated with recombinant WNT5B changed from flat to spindle-like. Recombinant WNT5B also increased α-smooth muscle actin and inhibited the expression of vascular endothelial-cadherin but retained characteristics of endothelial cells. The results suggest that WNT5B functions in the partial endothelial-mesenchymal transition (EndoMT). Furthermore, WNT5B-induced tube formation was impaired in the LECs following the knockdown of EndoMT-related transcription factor, SNAIL or SLUG. The WNT5B-induced expression of Snail or Slug was abolished by IWR-1-endo and Rac1 inhibitors, which are involved in the WNT/ß-catenin and planar cell polarity pathways, respectively. Collectively, the data suggest that WNT5B induces tube formation by regulating the expression of Snail and Slug proteins through activation of canonical and non-canonical WNT signalling pathways.
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Células Endoteliales/metabolismo , Transición Epitelial-Mesenquimal , Linfangiogénesis , Proteínas Wnt/metabolismo , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Permeabilidad de la Membrana Celular/genética , Movimiento Celular/genética , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/genética , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Linfangiogénesis/genética , Metástasis Linfática , Masculino , Ratones , Neoplasias de la Boca/genética , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Interferencia de ARN , Transducción de Señal , Factores de Transcripción de la Familia Snail/metabolismo , Proteínas Wnt/genética , Vía de Señalización Wnt , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study aimed to investigate the effects of the house dust mite allergen Der p 1 on the secretion of tryptase from the human mast cell line HMC-1. Flow cytometry was used to determine the expression levels of protease-activated receptor-2 (PAR2) on the surface of HMC-1 cells. HMC-1 cells were treated with Der p 1, SLIGRL-NH2 (PAR2 agonist), LRGILS-NH2 (control peptide for PAR2), or Der p 1 + FSLLRY (PAR2 antagonist), and the tryptase levels were measured using enzyme-linked immunosorbent assay. The biological functions of PAR2 were determined using the calcium green indicator, and intracellular calcium fluorescence intensity in the different groups (Der p 1, SLIGRL-NH2, LRGILS- NH2, Der p 1 + FSLLRY, tryptase, tryptase + FSLLRY, or cell culture medium) was detected by laser scanning confocal microscopy. The mast cells expressed PAR2 receptor on their surfaces. Der p 1 alone induced a significant release of intracellular calcium and tryptase in HMC-1 cells compared with the SLIGRL- NH2 treatment group and the control group. The combination of Der p 1 and FSLLRY partly inhibited intracellular calcium and tryptase release in HMC-1 cells compared with the Der p 1 treatment group. Moreover, tryptase induced a significant release of intracellular calcium in the HMC-1 cells. Der p 1 induced HMC-1 cell degranulation and the release of tryptase by activating the PAR2 receptor on the cell surfaces. Tryptase activated the PAR2 receptor and induced intracellular calcium release from the HMC-1 cells in a positive feedback loop.