RESUMO
Introduction: Artesunate, a derivative of artemisinin, has anti-malarial effects, and in recent years has also been reported to have anti-tumor activity. However, its anti-tumor mechanisms are not well understood. Methods: In this study, we focused on the targeting of Hsp90 by artesunate to inhibit tumor cell proliferation, which we examined using immunoprecipitation, a proliferation assay, flow cytometry, western blotting, a tumor xenograft animal model, and immunohistochemistry. Furthermore, to examine the tumor-suppressive effects of artesunatein nude mice, we used artesunate-loaded PLGA-PEG nanoparticles. Results: The binding of artesunate to Hsp90 was found to reduce the expression of its client proteins AKT, ERK, p-AKT, p-ERK, and EGFR, thereby blocking the cell cycle at the G0/G1 â S stage in lymphoma cells and inducing apoptosis. In addition, the results of tumor xenograft experiments revealed that artesunate reduced the expression of AKT and ERK proteins in tumor tissues, inhibited tumor proliferation, and reduced tumor size and weight. Furthermore, nanoparticle encapsulation was demonstrated to enhance the anti-cancer activity of artesunate. Discussion: We thus established that artesunate inhibits the proliferation of lymphoma cells by targeting the Hsp90 protein, and we accordingly believe that this compound has potential for development as a novelanti-tumor drug.
RESUMO
Physalis pubescens L. is an annual or perennial plant in the family Solanaceae It is used in traditional medicine for treating sore throats, coughs, urinary discomfort, and astringent pain, and externally for pemphigus and eczema in northern China. The proliferation inhibitory activity and mechanisms of the ethyl acetate extract (PHY-EA) from the leaves of Physalis pubescens were investigated. High performance liquid chromatography was used to identify the chemical composition of PHY-EA; sulforhodamine B was used to detect the proliferation inhibitory effect of PHY-EA on MCF-7, CA-46, Hela, HepG2, B16, and other tumor cells; flow cytometry was used to detect the effect of PHY-EA on the lymphoma cell cycle and apoptosis; Western blot was used to detect the expression of the cycle- and apoptosis-related proteins. The expression of Ki-67 and cleaved caspase 3 was detected by immunohistochemistry. The results showed that PHY-EA contained physalin B, physalin O, and physalin L. PHY-EA blocked the cell cycle of G2/MâG0/G1 in lymphoma cells and induced apoptosis in tumor cells. Mouse transplantation tumor experiments showed that PHY-EA had a significant inhibitory effect on mouse transplantation tumors, and the tumor volume and weight were significantly reduced. In conclusion, PHY-EA has a good antiproliferative effect on Burkkit lymphoma, indicating its potential medicinal value.
RESUMO
Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.
Assuntos
Masculino , Criança , Lactente , Feminino , Humanos , Estudos Retrospectivos , Hibridização in Situ Fluorescente , Prognóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Cariótipo Anormal , RecidivaRESUMO
<p><b>OBJECTIVE</b>To explore the mechanism of immunomodulatory activity of triptolide on primary immune thrombocytopenia (ITP)patients-derived plasmacytoid dendritic cells (pDCs).</p><p><b>METHODS</b>pDCs in peripheral blood of ITP patients before therapy (group 1), ITP patients in complete response (ITP-CR, group 2) and healthy donors (group 3) were sorted by flow cytometry, then incubated with triptolide at 0, 5, 10 or 30 µg/L. After 24 hours, we collected the supernatants and then detected the concentrations of IFN-α, IL-6 and TNF-α using ELISA. After 5 days, the cultured cells were collected and CD11c, CD80 and CD86 expressions of myeloid dendritic cells (mDCs) were analyzed by flow cytometry, the morphology of mDC was observed by light microscope and electron microscope.</p><p><b>RESULTS</b>After incubation with triptolide at 10 µg/L, the levels of IFN-α, IL-6 and TNF-α in group 1 \[(451.32 ± 85.77) ng/L, (105.68 ± 23.85) ng/L and (135.78 ± 30.62) ng/L\] and group 2 \[(391.71 ± 72.49) ng/L, (84.73 ± 17.77) ng/L and (108.16 ± 23.21) ng/L\] were significantly higher than those in group 3 \[(335.51 ± 67.54) ng/L, (73.62 ± 21.82) ng/L and (95.58 ± 32.85) ng/L\] (all P < 0.05); the levels of IFN-α, IL-6 and TNF-α in group 1 were significantly higher than those in group 2 (all P < 0.05) in a dose-dependent manner (P < 0.05). CD11c, CD80 and CD86 expressions of mDC in group1 and group 2 were significantly higher than those in group 3 (all P < 0.05); CD11c, CD80 and CD86 expressions of mDC in group 1 were significantly higher than those in group 2 (all P < 0.05) also in a dose-dependent manner (all P < 0.05). Triptolide could inhibit pDCs from differentiation into mDCs, the latter displayed more immature morphology than untreated-pDCs.</p><p><b>CONCLUSION</b>Triptolide could decrease the immune function of pDCs from ITP, inhibit pDCs from differentiation and maturation.</p>
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Casos e Controles , Diferenciação Celular , Células Cultivadas , Células Dendríticas , Biologia Celular , Diterpenos , Farmacologia , Compostos de Epóxi , Farmacologia , Fenantrenos , Farmacologia , Trombocitopenia , Alergia e ImunologiaRESUMO
<p><b>OBJECTIVE</b>To investigate the reliability and validity of the simplified Chinese version of Epworth sleepiness scale(ESS).</p><p><b>METHODS</b>Five hundred and eighty-five patients with suspected obstructive sleep apnea hypopnea syndrome (OSAHS) and 103 OSAHS patients who underwent operations were included in this study. The ESS was filled before polysomnography (PSG) monitoring under the direction of professional technicians. The patients who underwent operations did both PSG and ESS tests more than 6 months after operation. Fifty-one patients who underwent PSG at our hospital from July to August, 2010 were chosen to assess the ESS test-retest reliability on two separate occasions at least more than one week.</p><p><b>RESULTS</b>The total Cronbach's Alpha of ESS was 0.814. The test-retest reliability of ESS total scores was 0.679 and for each item was from 0.473 to 0.698(P < 0.01). Split-half reliability was 0.817 (P < 0.01). In the analysis of discriminant validity with apnea hypopnea index (AHI), the ESS total scores and each item's scores had significant differences in severity in OSAHS patients and simple snoring patients (P < 0.05), and this was also true in different degrees of lowest saturation of arterial oxygen (LSaO(2)) patients and normal LSaO(2) patients (P < 0.05). The factor analysis of construct validity showed that 4 factors were extracted. The cumulative proportion was 74.270%. The loading was higher than 0.4 among every item. The correlation coefficiency of overall ESS scores and each item's scores was relatively high except the last item. The ESS had low consistency with clinical diagnosis(κ = 0.099, P < 0.01) and the predictive validity was not good (r = 0.138, P < 0.01).As for 103 patients who had operations, the initial assessment of total ESS scores were 15.0[10;20] (M[P(25); P(75)]), and improved to 4[1;6] after operation. The patients who got effective results had significant difference in the total ESS scores before and after operation (Z = -7.528, P < 0.01), so was the patients who got ineffective results (Z = -4.382, P < 0.01) .</p><p><b>CONCLUSIONS</b>The simplified Chinese version of ESS had a good reliability and validity. It can be used to evaluate the chance of dozing in the daytime.</p>
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Povo Asiático , Análise Fatorial , Idioma , Letargia , Polissonografia , Reprodutibilidade dos Testes , Apneia Obstrutiva do Sono , Cirurgia Geral , Fases do Sono , Inquéritos e QuestionáriosRESUMO
<p><b>OBJECTIVE</b>To investigate the clinical and biological characteristics and prognosis of mixed phenotype acute leukemia (MPAL).</p><p><b>METHODS</b>Thirty two patients were diagnosed as MPAL by bone marrow examination, immunophenotyping, cytogenetic and molecular assay and were treated with combined chemotherapy regimens for both acute lymphoblastic and acute myeloid leukemia. Two cases were received allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>RESULTS</b>(1) The incidence of MPAL in acute leukemias was 2.6%. There were 16 cases (50.0%) of mixed myeloid and B-lymphoid (M/B), 14(43.8%) myeloid and T-lymphoid (M/T), one each (3.1%) of trilineage (M/B/T) and B- and T-lymphoid (B/T) phenotype. (2) The positive rates of CD34 and HLA-DR were 87.5% and 62.5%, respectively. (3) Abnormal karyotypes were detected in 70.0% of 30 MPAL patients, which were structural and numerical abnormalities including t(9;22), 11q23 and complex karyotypes. (4) The total complete remission (CR) rate was 75.0% and the overall survival (OS) and disease-free survival (DFS) at 2 years were 14.8% and 14.2% respectively. The CR rates for M/B and M/T cases were 75.0% and 71.4% respectively. No statistical difference was observed in OS and DFS between M/B and M/T cases.</p><p><b>CONCLUSIONS</b>MPAL is a rare type of acute leukemia with a high heterogeneity. The unfavorable indicators of MPAL may be factors such as abnormal karyotypes, high expression of CD34 and extramedullary infiltration. Combined regimens and more intensive therapy including allo-HSCT might contribute to improving survival.</p>
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Imunofenotipagem , Cariótipo , Leucemia Aguda Bifenotípica , Classificação , Genética , Alergia e Imunologia , Leucemia Mieloide Aguda , Genética , Alergia e Imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Genética , Alergia e Imunologia , PrognósticoRESUMO
<p><b>OBJECTIVE</b>To report a case of pure erythroid leukemia.</p><p><b>METHODS</b>The clinical features, treatment and prognosis of a rare case of pure erythroid leukemia were reported, and the related literature was reviewed.</p><p><b>RESULTS</b>The pure erythroid leukemia patient was diagnosed by 90.4% pronormoblasts in bone marrow, 99.5% for erythroid antigen CD71, 67.4% for glycophorin A were detected, while no differentiation antigen of myeloid, lymphoid and megakaryocyte lineages were observed. HAG (homoharringtonine + Cytarabine and G-CSF) regimen were administered with no effect. The patient developed multiple organ failure and died soon.</p><p><b>CONCLUSION</b>Pure erythroid leukemia has a fulminant clinical course with poor response to chemotherapy and worse prognosis.</p>
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Leucemia Eritroblástica Aguda , Terapêutica , PrognósticoRESUMO
<p><b>OBJECTIVE</b>To study the value of Epworth sleepiness scale in assessment of obstructive sleep apnea hypopnea syndrome (OSAHS) severity.</p><p><b>METHODS</b>The polysomnography (PSG) data of 620 suspected OSAHS patients from Jan. 2000 to Dec. 2003 were retrospectively analyzed. There were 556 males and 64 females, and their age ranged from 21 to 79 years (median 45.0 years). Of the all 620 patients, the median of the weight was 82.0 kg ( range 50 to 130 kg), median of height was 172.0 cm (range 147 to 178 cm), median of body mass index was 28.0 (range 18.5 to 42.9), median of apnea-hypopnea index (AHI) was 37.2 (range 0 to 126.1), median of lowest arterial oxygen saturation (LSAT) was 0.75 (range 0.21 to 0.93), median of ESS was 13.0 (range 0 to 24). OSAHS was diagnosed in 513 patients and simple snorer was diagnosed in 107 patients by PSG. All the patients filled in ESS questionnaire in sleep disorder centre before PSG.</p><p><b>RESULTS</b>The correlation coefficients of the ESS and AHI, LSAT was -0.314 and -0.312 respectively (P <0. 05). The median of ESS in severe OSAHS group was higher than that in simple snorer, mild and moderate OSAHS groups (P < 0.001), but no difference was found among the simple snorer, mild and moderate OSAHS groups (P < 0.05). The median of ESS in severe hypoxemia group was higher than that in no, mild and moderate hypoxemia groups (P < 0.001), but no difference was found among no, mild and moderate hypoxemia groups (P > 0.05).</p><p><b>CONCLUSIONS</b>The Epworth sleepiness scale has little value in assessment of OSAHS severity. A new sleepiness scale method which is suitable for Chinese should be made.</p>