RESUMO
Objective: To analyze the incidence of cytokine release syndrome (CRS) and its impact on the prognosis of patients with relapsed and refractory multiple myeloma (RRMM) following treatment with chimeric antigen receptor T-cell (CAR-T) therapy. Methods: A retrospective collection was conducted of the clinical data of 91 patients with RRMM who underwent CAR-T therapy at the Affiliated Hospital of Xuzhou Medical University from January 2020 to October 2022. Before CAR-T cell infusion, the patient underwent pretreatment with the fludarabine plus cyclophosphamide (FC) regimen. On day 0 (d0), the patient received a dose of 1×106 cells/kg of CAR-T. The occurrence of CRS was recorded post-treatment and graded accordingly, with grades 1 to 2 indicating mild CRS and grade≥3 indicating severe CRS. The follow-up cut-off date was February 14, 2023, with a median follow-up time [M (Q1, Q3)] of 14.1 (3.1, 37.7) months. Kaplan-Meier survival curve analysis assessed the progression-free survival (PFS) and overall survival (OS) of Grade 1 and Grade 2 CRS patients. Furthermore, univariate logistic regression analysis was conducted to identify factors associated with the development of severe CRS. Results: In a cohort of 91 patients diagnosed with RRMM, there were 51 male and 40 female individuals, with a median age [M (Q1,Q3)] of 57 (31, 73) years. All 91 cases (100%) experienced CRS, with 82 cases (90%) classified as mild (grades 1-2) CRS and 9 cases (10%) classified as severe (grades 3-5) CRS. In a study involving 9 patients with severe CRS, 8 cases resulted in mortality. The Kaplan-Meier survival curve analysis revealed that among grade 1 CRS patients, neither the median PFS nor the median OS was achieved. For grade 2 CRS patients, the median PFS was 12 months (95%CI: 4-not achieved), and the median OS was 21 months (95%CI: 4-not achieved). The progression-free survival and overall survival rates of grade 2 CRS patients were both lower than those of grade 1 CRS patients (both P<0.05). Single-factor logistic regression analysis revealed that a high tumor burden (OR=1.025, 95%CI: 1.002-1.049, P=0.031), a prolonged duration of CRS onset (OR=0.809, 95%CI: 0.646-0.971, P=0.037) and persistence (OR=1.758, 95%CI: 1.349-2.481, P=0.001) were identified as significant factors associated with severe CRS in patients with RRMM. Conclusions: Patients with RRMM who undergoes CAR-T therapy have a high incidence of CRS, with a higher mortality rate among those experiencing severe CRS. Furthermore, patients with grade 2 CRS exhibit lower rates of progression-free survival and overall survival compared to those with grade 1 CRS. Factors associated with the development of severe CRS in RRMM patients include high tumor burden and prolonged duration and onset of CRS.
Assuntos
Síndrome da Liberação de Citocina , Imunoterapia Adotiva , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Prognóstico , Síndrome da Liberação de Citocina/etiologia , Estudos Retrospectivos , Feminino , Masculino , Receptores de Antígenos Quiméricos , Pessoa de Meia-Idade , Idoso , AdultoRESUMO
Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy. Methods: A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results: Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG (χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG (χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion: Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Mieloma Múltiplo , Transplante Autólogo , Humanos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Feminino , Imunoterapia Adotiva/métodos , Idoso , Adulto , Resultado do Tratamento , Receptores de Antígenos QuiméricosRESUMO
OBJECTIVE: To illustrate the role of long non-coding RNA (lncRNA) TUG1 in the influence of the progression of cervical cancer (CC) and its underlying mechanism. PATIENTS AND METHODS: TUG1 level in CC tissues and adjacent normal ones was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Its level in CC patients with different tumor, node, and metastasis (TNM) staging and the tumor sizes were detected as well. The prognostic potential of TUG1 in CC was assessed by introducing the receiver operating characteristic (ROC) curves. The influences of TUG1 on proliferative and migratory abilities of HeLa and SiHa cells were evaluated. The subcellular distribution of TUG1 in CC cells was analyzed. Subsequently, the relative level of PUM2 (Pumilio2) in CC tissues and cell lines was examined. The prognostic potential of PUM2 in CC was assessed. RNA immunoprecipitation (RIP) and RNA pull-down were conducted to uncover the interaction between TUG1 and PUM2. Finally, the regulatory effect of TUG1/PUM2 axis on the viability of the CC cells was investigated. RESULTS: TUG1 was upregulated in CC, especially in those with worse TNM staging and larger tumor size. The overexpression of TUG1 enhanced proliferative and migratory abilities of Hela and SiHa cells. TUG1 was mainly distributed in the cytoplasm. PUM2 interacted with TUG1 and its level was positively regulated by TUG1. The silence of PUM2 reversed the promotive effect of TUG1 on the viability of the CC cells. CONCLUSIONS: TUG1 is upregulated in CC, which aggravates the progression of CC by interacting with PUM2.
Assuntos
RNA Longo não Codificante/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias do Colo do Útero/metabolismo , Western Blotting , Células Cultivadas , Colo do Útero/metabolismo , Progressão da Doença , Feminino , Humanos , Imunoprecipitação , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/patologiaRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) may cause potentially lethal infections. Increasing evidence suggests that the gut microbiota is associated with human health. Yet, whether patients with MRSA infections carry specific signatures in their fecal microbiota composition has not been determined. Thus, this study aimed to compare the fecal microbiota profile of MRSA-positive patients (n=15) with individuals without MRSA infection (n=15) by using the PacBio single molecule, real-time (SMRT) DNA sequencing system and real-time quantitative polymerase chain reaction (qPCR). Mann-Whitney tests and unweighted UniFrac principal coordinate analysis (PCoA) showed that the profile of fecal microbiota was apparently different between the two populations. Both the community richness and diversity were reduced in the MRSA-positive group (p<0.050). The genera Acinetobacter and Enterococcus were highly enriched in the MRSA-positive group, whereas less short-chain fatty acid (SCFA)-producing bacteria, including Butyricimonas, Faecalibacterium, Roseburia, Ruminococcus, Megamonas and Phascolarctobacterium, were detected in the MRSA-positive group. At species level, the species Acinetobacter baumannii and Bacteroides thetaiotaomicron were prevalent in the MRSA-positive group, whereas opposite trends were observed in 17 other species, such as Faecalibacterium prausnitzii, Lactobacillus rogosae, Megamonas rupellensis and Phascolarctobacterium faecium. Positive correlations were observed between Acinetobacter baumannii and erythrocyte sedimentation rate (ESR) (R=0.554, p=0.001), as well as hypersensitive C reactive protein (hsCRP) (R=0.406, p=0.026). Faecalibacterium prausnitzii was negatively associated with ESR (R=-0.545, p=0.002), hsCRP (R=-0.401, p=0.028) and total bile acids (TBA) (R=-0.364, p=0.048). In conclusion, the fecal microbiota structure was different between MRSA-positive and -negative patients. The increase in potential pathogens with the reduction of beneficial populations, such as SCFA-producing bacteria, in MRSA-positive patients may affect prognosis.
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Biota , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Adulto JovemRESUMO
The protective effect of swerchirin, a purified xanthone isolated from whole herb of Swertia calycina Franch. on hematopoiesis was investigated. A significant increase of colony formation in the spleen (colony forming unit in spleen = CFU-S) of mice irradiated with 550 rad 60Co gamma-rays and an enhancement of proliferative response of BMC to rmGM-CSF treated with swerchirin [10 mg/kg, 3 time/wk, i.p.] was observed. After introduction of swerchirin [10 mg/kg, i.p. once] a significant increase in the number of peripheral blood leukocytes and a rise in the serum of colony stimulating factor (CSF) were also confirmed. The types of CSF in serum were M-CSF and other hematopoietic growth factors, which were confirmed using McAb of IL-3, GM-CSF and PcAb of M-CSF. These beneficial effects of swerchirin on hematopoiesis may be related to its activity inducing CSFs and other hematopoietic growth factors, and warrant further evaluation of its usefulness.
Assuntos
Radioisótopos de Cobalto , Hematopoese/efeitos dos fármacos , Xantenos/farmacologia , Xantonas , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos da radiação , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Células Cultivadas , Fatores Estimuladores de Colônias/sangue , Fatores Estimuladores de Colônias/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Hematopoese/efeitos da radiação , Contagem de Leucócitos/efeitos dos fármacos , Contagem de Leucócitos/efeitos da radiação , Camundongos , Camundongos Endogâmicos BALB C , Plantas Medicinais/química , Proteínas Recombinantes , Baço/citologia , Baço/efeitos dos fármacos , Baço/efeitos da radiaçãoRESUMO
OBJECTIVE: To discuss the problem of classifying Curcuma for Medical purposes. METHOD: RAPD was used to detect the DNA polymorphism within and among Curcuma wenyujin, C. sichuanensis and C. aromatica. RESULT: It is hard to differentiate between C. wenyujin and C. sichuanensis from the DNA level. The relationship between C. wenyujin and C. aromatica was also analyzed. CONCLUSION: Based on the morphological and chemical data, it is suggested that these two species should be combined into one and that classification based on peduncle central or peduncle lateral may not be right. This method will help to some degree to solve the problem of certifying the medicinal plant Curcuma.