RESUMO
BACKGROUND@#Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications.@*METHODS@#We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome.@*RESULTS@#Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death.@*CONCLUSION@#CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.
RESUMO
Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH).However,little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy,and whether specific hypertrophyrelated microRNAs are involved in the modulation.MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia.This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy.H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days.The size of cardiomyocytes,and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR,respectively.MiR-31 mimic or Ro 31-8220,a specific inhibitor of protein kinase C epsilon (PKCε),was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes.PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting.The results showed that CIH induced obvious enlargement of cardiomyocytes,which was paralleled with increased atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels.All these changes were reversed by the treatment with atorvastatin.Meanwhile,miR-31 was increased by CIH in vitro.Of note,the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31.Moreover,overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes.Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε.These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.
RESUMO
Atorvastatin is proven to ameliorate cardiac hypertrophy induced by chronic intermittent hypoxia (CIH).However,little is known about the mechanism by which atorvastatin modulates CIH-induced cardiac hypertrophy,and whether specific hypertrophyrelated microRNAs are involved in the modulation.MiR-31 plays key roles in the development of cardiac hypertrophy induced by ischemia/hypoxia.This study examined whether miR-31 was involved in the protective role of atorvastatin against CIH-induced myocardial hypertrophy.H9c2 cells were subjected to 8-h intermittent hypoxia per day in the presence or absence of atorvastatin for 5 days.The size of cardiomyocytes,and the expression of caspase 3 and miR-31 were determined by Western blotting and RT-PCR,respectively.MiR-31 mimic or Ro 31-8220,a specific inhibitor of protein kinase C epsilon (PKCε),was used to determine the role of miR-31 in the anti-hypertrophic effect of atorvastatin on cardiomyocytes.PKCε in the cardiomyocytes with miR-31 upregulation or downregulation was detected using RT-PCR and Western blotting.The results showed that CIH induced obvious enlargement of cardiomyocytes,which was paralleled with increased atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP),and slow/beta cardiac myosin heavy-chain (MYH7) mRNA levels.All these changes were reversed by the treatment with atorvastatin.Meanwhile,miR-31 was increased by CIH in vitro.Of note,the atorvastatin pretreatment significantly increased the mRNA and protein expression of PKCε and decreased that of miR-31.Moreover,overexpression of miR-31 abolished the anti-hypertrophic effect of atorvastatin on cardiomyocytes.Upregulation and downregulation of miR-31 respectively decreased and increased the mRNA and protein expression of PKCε.These results suggest that atorvastatin provides the cardioprotective effects against CIH probably via up-regulating PKCε and down-regulating miR-31.
RESUMO
Objective To understand the antimicrobial susceptibility profiles,serotype distribution and virulence genes.Methods A total of 515 group B Streptococcus (GBS) including 108 virulence,112 non virulence,and 295 colonizing isolates were collected in four Shenzhen hospitals.Isolates were characterized by conventional and molecular serotyping.The virulence genes of scpB,lmb,hylB,cylE,bac,bca and rib of GBS isolates were detected by PCR.Antimicrobial susceptibility to penicillins,macrolides,lincosamides,quinolones and tetracyclines was tested using disk diffusion and the MICs for penicillin were determined by E test.Results Molecular serotyping for all eight serotypes (Ⅰa,Ⅰb,Ⅱ ～ Ⅵ,Ⅸ) was in full accordance with conventional serotyping.Taking MS and CS together,serotype Ⅲ was the most common capsular type (56.5 ％),followed by Ⅰb (17.5 ％),Ⅰa (12.6 ％),V (7.4 ％),Ⅱ (2.7 ％),Ⅵ (1.4 ％),Ⅳ (1.0 ％) and Ⅸ (1.0 ％).Serotype Ⅲ was the main serotype in different groups,serotype Ⅰ a was significantly more common among patients with invasive infections (11.1％) and no invasive infections (29.5％),serotype Ⅰb isolates were significantly more common among clone (19.3％).Virulence gene screening using PCR method showed the presence of cylE,lmb,scpB and hylB in almost all the isolates,while rib,bca and bac genes were found in 29.1％,14.6％ and 9.7％ of the isolates.Certain genes were significantly associated with specific serotypes,for example,rib with serotypes Ⅲ,Ⅰa and Ⅰb,bca and bac with serotypes Ⅲ and Ⅰb.Drug susceptibility results showed that GBS susceptibility to β lactam antimicrobials was prevalent (100 ％).Resistance rates for erythromycin,clindamycin and tetracycline were 67.0 ％,61.9 ％ and 86.0 ％,respectively.Conclusion Serotype distribution,virulence genes and antimicrobial susceptibility profiles of GBS contributes to the clinical therapy,epidemiological studies and design of Vaccines.
RESUMO
Oncomelania is the only intermediate host of Schistosoma japonicum as well as an indispensable part of schistosomiasis transmission. Now synthetic molluscicides have a lot of problems, such as high cost of production, chemical pollution, drug resistance, and toxicity to non-target body, which makes people's interest turn to plants and plant-derived compounds. This paper describes the current existence of chemical snail control methods and biological snail control methods on the view of chemical construction, mechanism of action, and structure-activity relationships of natural extracts with molluscicidal activity, in order to provide the basis for the development of the new plant molluscacide.
RESUMO
OBJECTIVE@#The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma.@*METHOD@#Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P 0.05). IC + RT + AC group had heavier acute toxicity effects than other groups, but it did not affect the treatment process, all patients could be tolerated.@*CONCLUSION@#This retrospective study has demonstrated that alternating Chemo-radiotherapy and early radiotherapy not only can improve the survival rate for locally Advanced Nasopharyngeal Carcinoma, but also have slight toxicities and side reaction, all patients may tolerated.
Assuntos
Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Carcinoma , Quimioterapia Adjuvante , Cisplatino , Intervalo Livre de Doença , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Tratamento Farmacológico , Mortalidade , Patologia , Radioterapia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
<p><b>OBJECTIVE</b>To investigate whether whole tumor cell vaccination strategies in combination with bone marrow transplantation (BMT) can stimulate graft-versus-tumor effect (GVT).</p><p><b>METHODS</b>Twenty-six BALB/c mice were randomly divided into 3 groups: BMT group (group A, n = 10), BMT + vaccination group (group B, n = 10), control group (group C, n = 6). (BALB/c × C57BL/6) F1 mice [CB6F1, H-2K(b/d)] were used as donors. BALB/c mice of group C were only inoculated with Renca cell (2.6 × 10(6)). Mice of group A and B were conditioned with 8 Gy irradiation, followed by infusion by bone marrow cell of CB6F1 mice on day 1, then inoculated with Renca cell (2.6 × 10(6)) on day 8. All mice of group B were immunized subcutaneous on the back with 5 × 10(5) irradiated Renca tumor cells on day 9 and day 16. All mice of group C were inoculated with Renca cell (2.6 × 10(6)) on day 8. In group A and B, all mice were analyzed by fluorescence activated cell sorter (FACS) on day 14, and 28 day after BMT. Mice were killed on day 32 after inoculation with tumor cell and collected blood sample. All tumors were taken out to be weighed and then fixed in 10% buffered formalin, embedded in paraffin, and cut into 5 µm slices. The slices were stained with HE and examined by TdT mediated-dUTP nick end labeling (TUNEL). Liver, skin, intestine, and spleen were biopsied for histopathological examination.</p><p><b>RESULTS</b>The results of chimera showed that engraftments of group A, B were full donor chimerism, and the chimerism of those remained above 90% and preserved even after 28 days. The tumor weight, tumor volume increment in the group B was lower than group A and C (P < 0.05). The tumor suppressing rates of the group A and B were 54%, 60% respectively. The area ratio of tumor necrosis and apoptosis index (AI) of the tumor in the group B were higher than group A and C (P < 0.05). Graft-versus-host disease was not observed in each group.</p><p><b>CONCLUSION</b>The mechanism of GVT after haploidentical allogeneic bone marrow transplantation with tumor vaccination may be the promotion of tumor necrosis and apoptosis.</p>
Assuntos
Animais , Masculino , Camundongos , Transplante de Medula Óssea , Alergia e Imunologia , Vacinas Anticâncer , Alergia e Imunologia , Carcinoma de Células Renais , Alergia e Imunologia , Terapêutica , Células Cultivadas , Modelos Animais de Doenças , Efeito Enxerto vs Tumor , Alergia e Imunologia , Neoplasias Renais , Alergia e Imunologia , Terapêutica , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Quimeras de Transplante , Alergia e ImunologiaRESUMO
The objective of this study was to investigate the effect of ligustrazine on the expression of stem cell factor mRNA (SCF) in bone marrow tissue and explore the mechanism of hematopoietic reconstitution after bone marrow transplantation (BMT). The colony forming unit of spleen (CFU-S) were counted, the survival rate at days 7, 14 and 21 after BMT were measured, as well as the expression level of SCF mRNA was detected by RT-PCR. The results showed that in ligustrazine group CFU-S counts on day 10 and survival rate, expression level of SCF mRNA on day 7, 14 and 21 after BMT were higher than that in the control group (p < 0.01 or p < 0.05). In conclusion, ligustrazine promotes the recovery of hematopoietic cells in bone marrow, enhances the repair of bone marrow microvessels, and then improves bone marrow microenvironment and promotes hematopoietic reconstitution.
Assuntos
Animais , Masculino , Camundongos , Transplante de Medula Óssea , Hematopoese , Camundongos Endogâmicos BALB C , Pirazinas , Farmacologia , RNA Mensageiro , Genética , Metabolismo , Fator de Células-Tronco , Genética , Metabolismo , Transplante IsogênicoRESUMO
<p><b>OBJECTIVE</b>To explore the relationship between the expression of caspase-3 in testicular germ cells of rats with experimental left varicocele (ELV) and apoptosis of germ cells.</p><p><b>METHODS</b>Twenty-four male SD rats were randomly divided into three groups with eight animals each: sham-operation group (SOG), 30-day post-operation group (PG1) and 60-day psot-operation group (PG2). ELV model was established by the partial ligation of the left renal vein. To detect apoptosis of germ cells and expression of caspase-3, TUNEL assay and immunohistochemistry (SABC) were used respectively.</p><p><b>RESULTS</b>The number of caspase-3 positive germ cells per tubular cross section in left and right testes of rats in SOG, PG1, PG2 were 0.1175 +/- 0.0129, 0.2463 +/- 0.0421, 0.2938 +/- 0.0511 and 0.1650 +/- 0.0192, 0.2538 +/- 0.0219, 0.2775 +/- 0.0343, respectively. Compared with SOG, the expression of caspase-3 in bilateral testes of rats in PG1 and PG2 were increased, and the differences were statistically significant(P = 0.0115 and P = 0.0144).</p><p><b>CONCLUSION</b>Expression of caspase-3 protein increased in germ cells of rats with ELV, which may be one of the molecular mechanisms related to excessive testicular germ cell apoptosis.</p>
Assuntos
Animais , Masculino , Ratos , Apoptose , Caspase 3 , Modelos Animais de Doenças , Células Germinativas , Biologia Celular , Metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Varicocele , Metabolismo , Cirurgia GeralRESUMO
To explore the hematopoiesis inhibition mechanisms of interferon-gamma (IFN-gamma), the effects of IFN-gamma on the expression of the cyclin D in the umbilical cord blood hematopoietic stem/progenitor cells were observed. In the experiments the CD34(+) cells were isolated from the cord blood with MIDI-MACS system; semi-solid methylcellulose culture technique was used to measure the formation of CFU-GM; the expression levels of cyclin D isoforms were assayed by semi-quantitative RT-PCR, after the hematopoietic stem/progenitor cells were incubated with IFN-gamma. The results indicated that IFN-gamma could inhibit the formation of CFU-GM and down-regulate the expression of cyclin D2 and cyclin D3 at the mRNA level. It is concluded that the IFN-gamma could inhibit the proliferation of hematopoietic stem cells and down-regulate the expression of cyclin D, that may be one mechanism underlying the hematopoietic inhibition of IFN-gamma.