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1.
Front Immunol ; 15: 1338178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415259

RESUMO

Hematopoietic stem cells (HSCs) undergo self-renewal and differentiation in the bone marrow, which is tightly regulated by cues from the microenvironment. The gut microbiota, a dynamic community residing on the mucosal surface of vertebrates, plays a crucial role in maintaining host health. Recent evidence suggests that the gut microbiota influences HSCs differentiation by modulating the bone marrow microenvironment through microbial products. This paper comprehensively analyzes the impact of the gut microbiota on hematopoiesis and its effect on HSCs fate and differentiation by modifying the bone marrow microenvironment, including mechanical properties, inflammatory signals, bone marrow stromal cells, and metabolites. Furthermore, we discuss the involvement of the gut microbiota in the development of hematologic malignancies, such as leukemia, multiple myeloma, and lymphoma.


Assuntos
Medula Óssea , Microbioma Gastrointestinal , Animais , Medula Óssea/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Diferenciação Celular , Hematopoese
3.
Cell Biochem Funct ; 41(8): 1343-1356, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37823726

RESUMO

Hematologic malignancies are the most common hematopoietic diseases and a major public health concern. However, the mechanisms underlying myeloid tumors remain unknown owing to the intricate interplay between mutations and diverse clonal evolution patterns, as evidenced by the analysis of bulk cell-derived omics data. Several single-cell omics techniques have been used to characterize the hierarchies and altered immune microenvironments of hematologic malignancies. The comprehensive single-cell atlas of hematologic malignancies provides novel opportunities for personalized combinatorial targeted treatments, avoiding unwanted chemo-toxicity. In the present study, we performed transcriptome sequencing by combining single-cell RNA sequencing (scRNA-seq) with a targeted oncogenic gene panel for acute myeloid leukemia, overcoming the limitations of scRNA-seq in detecting oncogenic mutations. The distribution of oncogenic IDH1, IDH2, and KRAS mutations in each cell type was identified in the bone marrow (BM) samples of each patient. Our findings suggest that ferroptosis and metabolic reprogramming are involved in the tumorigenesis and chemotherapy resistance of oncogenic mutation-carrying cells. Biological progression via IDH1, IDH2, and KRAS mutations arrests hematopoietic maturation. Our study findings provide a rationale for using primary BM cells for personalized treatment in clinical settings.


Assuntos
Ferroptose , Neoplasias Hematológicas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Mutação , Análise de Sequência de RNA , Microambiente Tumoral
4.
Exp Hematol Oncol ; 12(1): 74, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37633955

RESUMO

Bispecific antibodies (BsAbs) and dual-targeted chimeric antigen receptor T (CAR T) cells have been employed in relapsed/refractory multiple myeloma (RRMM) patients over the past few years, as an increasing number of patients were ineffectively treated by ≥ 3 prior lines of therapy. BCMA/CD3 and GPRC5D/CD3 are the most popular combinations. Clinical findings indicated that patients exhibit a greater susceptibility to stronger and more enduring responses. Here, we summarize the latest data from the 2023 ASCO annual meeting on BsAbs targeting BCMA/CD3, GPRC5D/CD3 and BCMA/CD19 CAR T cells.

5.
Front Oncol ; 13: 1162413, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256185

RESUMO

Background: Whether autologous hematopoietic stem cell transplantation (ASCT) improves the survival of patients with peripheral T-cell lymphoma (PTCL) remains controversial. Some studies have demonstrated that the efficacy of ASCT is superior in patients with complete remission (CR), whereas patients with partial remission (PR) remain vulnerable to relapse after ASCT, resulting in decreased survival rates. Maintenance therapy after chemotherapy may reduce the relapse rate of PTCL and improve survival; however, the role of maintenance therapy after ASCT in PTCL remains unclear. In this study, we aimed to analyze the efficacy of ASCT and post-transplant maintenance therapy in PTCL. Methods: We retrospectively analyzed the clinical data of 69 patients with PTCL who underwent ASCT at our center between November 2001 and November 2021. According to the patients' intention, thirty patients received post-transplant maintenance treatment, whereas 39 did not. The overall survival (OS) and progression-free survival (PFS) between the groups were compared using the log-rank test. Results: At a median follow-up of 36 months, the entire cohort's 3-year OS and PFS were 67.8% and 53.0%, respectively. The 3-year OS and PFS of patients with CR1, CR2, and PR were 85.3% and 65.4%, 80.0% and 60.0%, and 38.4% and 32.0%, respectively (OS: P=0.001; PFS: P=0.003). The relapse rates between the groups with or without maintenance therapy were 26.7% vs. 52.2%, the 3-year OS was 86.0% vs. 54.2% (P=0.004), and the 3-year PFS was 73.3% vs. 37.5% (P=0.004). Further analysis revealed that the efficacy of maintenance therapy was not significant in patients with CR1 and CR2, whereas patients with PR benefited from maintenance therapy. The relapse rate of patients with PR who received or did not receive maintenance therapy was 33.3% vs. 78.7%, 3-year OS was 66.7% vs. 21.9% (P=0.007), and 3-year PFS was 66.7% vs. 12.5% (P=0.004). Conclusions: Patients with CR in PTCL benefit from ASCT, and post-transplant maintenance therapy reduces the relapse rate and significantly improves OS and PFS in patients with PR.

6.
Arch Med Res ; 54(4): 299-309, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37211508

RESUMO

BACKGROUND: Multiple myeloma (MM) presently remains largely incurable. The importance of circular RNAs (circRNAs) in various malignancies, including MM, has been demonstrated for decades. Our goal is to decipher the complex molecular mechanism of circ_0111738 in modulating MM progression. METHODS: Circ_0111738 and miR-1233-3p expressions in the collected MM cells and bone marrow aspirates were examined by qRT-PCR. CCK-8, transwell migration and invasion, and tube formation assays were performed to evaluate MM cell proliferation, migration and invasion, and angiogenesis, respectively. A tumor xenograft experiment was performed to validate the biofunction of circ_0111738's in vivo. The predicted interaction of circ_0111738 and miR-1233-3p's was determined by RNA immunoprecipitation (RIP) and luciferase reporter assays. Apoptosis-associated proteins and the HIF-1 pathway were investigated by western blotting. RESULTS: Circ_0111738 was poorly expressed in MM cells and patients. Overexpression of circ_0111738 reduced MM cell proliferation, migration, invasion, and angiogenesis while circ_0111738 led to opposite results. The anti-tumorigenic effect of circ_0111738 overexpression was also observed in vivo. RIP and luciferase experiments demonstrated that circ_0111738 interacted with miR-1233-3p in MM cells. The silencing of miR-1233-3p prevented the stimulation of malignant behaviors of MM cells induced by circ_0111738 silencing, including the expression of HIF-1α. CONCLUSION: Our data suggest that circ_0111738 functioned as a competing endogenous RNA (ceRNA) and suppressed the oncogenic function of miR-1233-3p in MM by inactivating the HIF-1 pathway. Therefore, up-regulation of circ_0111738 may be a promising therapy against MM.


Assuntos
MicroRNAs , Mieloma Múltiplo , RNA Circular , Humanos , Western Blotting , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , MicroRNAs/genética , Transdução de Sinais , RNA Circular/genética
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 515-519, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812423

RESUMO

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 µmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H2DCFDA probe labeling. RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G2/M phase was increased to 28% and 40%, respectively. The cells in bortezomib group also showed a similar distribution after being treated. After treated with PX-12 and bortezomib, the cells in G1 phase were decreased significantly to 19% and 12% in S phase, but increased significantly to 68% in G2/M phase, which was significantly different from PX-12 group and bortezomib group (P<0.01). After culture for 72 hours, the apoptosis rate was 71.3% in the combination group, which was significantly higher than that in PX-12 group, bortezomib group, and control group (20.6%, 33.3%, 10.6%)(P<0.01). After culture for 24 hours, the intracellular ROS level in the combination group was 12015±430.2, which was higher than that in the PX-12 group, bortezomib group, and control group (6729±352.8, 2651±228.3, 1098±164.6, respectively) (P<0.01). CONCLUSION: PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.


Assuntos
Mieloma Múltiplo , Apoptose , Bortezomib/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos
8.
Cell Cycle ; 19(23): 3289-3302, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33131409

RESUMO

Circular RNAs (circRNAs) possess important regulatory effects on multiple myeloma (MM) progression. Here, we aimed at exploring the function of circ_0007841 in MM and the underlying molecular mechanism. Expression of circ_0007841, microRNA (miR)-129-5p and Jagged1 (JAG1) was determined via qRT-PCR or western blot assay. Methyl thiazolyl tetrazolium (MTT) assay was applied to examine cell viability and IC50 value of MM cells to bortezomib (BTZ). Colony formation assay was performed to analyze cell proliferation. Moreover, cell apoptosis was assessed by flow cytometry and western blot analysis. Cell metastasis was evaluated by wound healing assay and Transwell assay. Function of circ_0007841 in vivo was determined by xenograft tumor assay. Target relationship between miR-129-5p and circ_0007841 or JAG1 was confirmed via dual-luciferase reporter, RNA immunoprecipitation (RIP) and pull-down assays. The up-regulation of circ_0007841 and JAG1, and the down-regulation of miR-129-5p were detected in MM bone marrow aspirates and cells. Circ_0007841 knockdown significantly repressed cell proliferation, chemoresistance, and metastasis, while contributed to apoptosis of MM cells in vitro, and reduced tumor growth in vivo. Circ_0007841 targeted miR-129-5p, and miR-129-5p inhibition reversed impact of silencing of circ_0007841 on MM cells. JAG1 was a mRNA target of miR-129-5p, whose overexpression could undermine the miR-129-5p-mediated effects on MM cells. Circ_0007841 positively regulated JAG1 expression via absorbing miR-129-5p. Circ_0007841 knockdown inhibited MM cell proliferation, metastasis and chemoresistance through modulating miR-129-5p/JAG1 axis, suggesting that circ_0007841 might serve as a potential therapeutic target of MM.


Assuntos
Bortezomib/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína Jagged-1/biossíntese , MicroRNAs/biossíntese , Mieloma Múltiplo/metabolismo , RNA Circular/antagonistas & inibidores , Idoso , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , Proteína Jagged-1/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/prevenção & controle , RNA Circular/genética , RNA Interferente Pequeno/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
9.
Aging (Albany NY) ; 12(19): 18970-18981, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33012724

RESUMO

Despite continuous improvements of AML therapy, the prognosis of AML patients remains unsatisfactory. Recently, lncRNAs have been reported to participate in the development of AML. Our data demonstrated that MMP15 and LINC00963 were upregulated and miR-608 was decreased in AML cells (THP-1, HL-60, HEL and MOLM-13) compared to HS-5 cells. RT-qPCR results showed that LINC00963 levels were higher in the serum and bone marrow of AML cases than in controls. Moreover, overexpression of LINC00963 promoted AML cell growth and EMT progression in both THP-1 and HL-60 cells. Furthermore, miR-608 levels were downregulated in the serum and bone marrow of AML cases compared with controls, and Pearson's correlation analysis indicated that LINC00963 was negatively correlated with miR-608 in the serum and bone marrow of AML samples. In addition, we demonstrated that LINC00963 sponged miR-608 expression and that MMP-15 was a target of miR-608 in AML cells. Finally, rescue experiments indicated that ectopic expression of LINC00963 accelerated cell growth and EMT development by modulating MMP-15. These data demonstrated that LINC00963 acted as an oncogene and may be a potential target for AML treatment.

10.
Cancer Cell Int ; 20: 383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782441

RESUMO

BACKGROUND: The pathogenesis of multiple myeloma (MM) is not completely known. Uncovering the potential mechanism of MM initiation and progression is essential for identifying novel diagnostic and therapeutic targets. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). Cell proliferation ability was analyzed through cell counting kit-8 (CCK8) assay, colony formation assay and flow cytometry. Transwell assays were conducted to measure the migration and invasion abilities of MM cells. Cell apoptosis was also assessed by flow cytometry. The interaction between miR-338-3p and circ_0007841 or BRD4 was confirmed by dual-luciferase reporter assay and RNA-pull down assay. RESULTS: Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cell lines than that in healthy volunteers and normal plasma cell line nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. miR-338-3p was a direct target of circ_0007841 in MM cells and circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells and miR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841. CONCLUSION: Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.

12.
Mol Cancer ; 18(1): 154, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31684964

RESUMO

Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies have dramatically changed the natural history of multiple myeloma (MM). However, most patients eventually suffer a relapse and succumb to the disease. Chimeric antigen receptor (CAR) engineered T cells targeting B cell maturation antigen (BCMA), CD138, CS1 glycoprotein antigen (SLAMF7) and light chains are in active development for therapy of refractory /relapsed (RR) MM. CD19- targeted CAR T cells in conjunction with autologous stem cell transplantation also showed activity in RRMM. Dual- target CAR T cells are in clinical trials for RRMM. This review summarized the recent updates of ongoing CAR T clinical trials for multiple myeloma.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/terapia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Animais , Antígenos CD19/imunologia , Antígenos de Neoplasias/imunologia , Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Antígeno de Maturação de Linfócitos B/imunologia , Antígeno de Maturação de Linfócitos B/metabolismo , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Humanos , Imunoterapia Adotiva/métodos , Mieloma Múltiplo/diagnóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética
13.
Cancer Manag Res ; 11: 8295-8302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571987

RESUMO

BACKGROUND: This study aims to compare the efficacy and adverse reactions of bortezomib for treating newly diagnosed multiple myeloma (MM) through two different administration methods: intravenous (IV) injection and subcutaneous (SC) injection. METHODS: A retrospective analysis was performed in 205 patients with newly diagnosed MM, who were treated by the Department of Hematopathology, Henan Cancer Hospital, from June 2009 to December 2017. These patients were divided into two groups according to the treatment methods: IV injection group, IV injection of bortezomib; SC injection group, SC injection of bortezomib. RESULTS: After the first course of treatment, the effect of very good partial remission (VGPR) or above (≥VGPR) in the IV injection group (IV group) and SC injection group (SC group) was 31.0% and 14.3%, respectively (P=0.004), while the overall response rate (ORR) was 72.0% and 49.5%, respectively (P=0.001). From the 2nd course to the 6th course of treatment, the ORR was not statistically different between these two groups. No significant difference was found in median progression-free survival (37 vs 45 months) and overall survival (63 vs 59 months). A lower frequency of adverse events, especially Grade 3 peripheral neuropathy, was observed in SC group compared with the IV group. CONCLUSION: Compared with IV administration, SC bortezomib can provide a better balance between efficacy and toxicity.

14.
Acta Haematol ; 142(4): 208-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163428

RESUMO

BACKGROUND: miR-886-5p plays an important role in many tumors, but it has been rarely investigated in multiple myeloma (MM). We studied the expression of miR-886-5p in the plasma of MM patients and in MM cell lines, and evaluated its biological function to identify its potential involvement in MM. METHODS: We recruited 16 subjects including 10 newly diagnosed MM patients who had not received treatment and 6 healthy individuals. The expression of miR-886-5p in plasma and MM cell lines was examined by quantitative reverse transcription polymerase chain reaction. Cell Counting Kit-8, colony formation assay, and 7-amino-actinomycin D/allophycocyanin double staining were performed to detect the function of miR-886-5p in MM cell lines. The expression of Bax and p53 was determined by western blot. RESULTS: The expression of miR-886-5p in the plasma of MM patients was higher than that in normal individuals and its level in MM cell lines was higher than that in peripheral blood mononuclear cells isolated from healthy individuals. miR-886-5p could trigger the cell proliferation and inhibition of apoptosis and affect the cell cycle. CONCLUSION: miR-886-5p triggered MM cell growth and may act as a diagnostic plasma biomarker for MM, potentially contributing to resistance to chemotherapy.


Assuntos
Biomarcadores Tumorais/sangue , Leucócitos Mononucleares/metabolismo , MicroRNAs/sangue , Mieloma Múltiplo/sangue , RNA Neoplásico/sangue , Adulto , Idoso , Apoptose , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/biossíntese , Proteína X Associada a bcl-2/biossíntese
15.
Artif Organs ; 43(10): 1028-1034, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30972806

RESUMO

This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre-transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post-transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow-up time was 27.6 months (4-96 months). The 3-year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post-transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre-transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre-transplantation (P = 0.013) and post-transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post-transplantation were independent prognostic factors of OS. At post-transplantation, CR and VGPR, ISS stage, and pre-transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post-transplantation are independent prognostic factors of OS and PFS, while pre-transplant induction therapy is an independent prognostic factor for PFS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
16.
Bone Marrow Transplant ; 54(6): 821-827, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30518982

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective measure for the treatment of hematological disease. With the progress and widespread use of allo-HSCT, Epstein-Barr virus (EBV) related central nervous system (CNS) diseases have gotten more and more attention because of its poor prognosis and overall survival. Since currently there is no standard treatment for patients with EBV-associated CNS diseases and reported therapies are heterogeneous with mixed results, we attempted to develop a novel therapeutic method. We applied a regimen of intrathecal donor lymphocyte infusion (IDLI) in three patients with EBV-associated CNS diseases after allo-HSCT in addition to immunosuppressants reduction and combined antiviral therapy. All of three patients were responsive to this therapy: all clinical symptoms and EBV load in CSF were resolved 10, 17, and 12 days after initial IDLI, respectively, and magnetic resonance imaging (MRI) showed that lesions of case 1 and 2 disappeared 15 and 19 days after initial IDLI, respectively. Even more appealing, there were no acute or chronic adverse reactions during the infusion and up to 23 months of follow-up. In conclusion, IDLI seems to be an effective and safe method for EBV-associated CNS diseases in allo-HSCT recipients. We recommend this treatment modality for further investigation.


Assuntos
Doenças do Sistema Nervoso Central/etiologia , Infecções por Vírus Epstein-Barr/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos/metabolismo , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Doenças do Sistema Nervoso Central/patologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Injeções Espinhais , Masculino , Doadores de Tecidos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Resultado do Tratamento , Adulto Jovem
17.
J Hematol Oncol ; 11(1): 132, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30482221

RESUMO

Currently, the two approved T cell products with chimeric antigen receptors (CAR) are from autologous T cells. These CAR T cells approved for clinical use must be generated on a custom-made basis. This case-by-case autologous T cell production platform remains a significant limiting factor for large-scale clinical application due to the costly and lengthy production process. There is also an inherent risk of production failure. The individualized, custom-made autologous CAR T cell production process also posts constriction on the wide application on diverse tumor types. Therefore, universal allogeneic T cells are needed for the preparation of universal CAR T cells that can serve as the "off-the-shelf" ready-to-use therapeutic agents for large-scale clinical applications. Genome-editing technologies including ZFN (zinc finger nuclease), TALEN (transcription activator-like effector nuclease), and CRISPR-Cas9 are being used to generate the universal third-party T cells. In addition, split, universal, and programmable (SUPRA) CARs are being developed to enhance the flexibility and controllability of CAR T cells. The engineered universal T cells and universal CARs are paving the road for a totally new generation of CAR T cells capable of targeting multiple antigens and/ or being delivered to multiple recipients without re-editing of T cells. This may escalate to a new wave of revolution in cancer immunotherapy. This review summarized the latest advances on designs and development of universal CARs, universal T cells, and clinical application of universal CAR T cells.


Assuntos
Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Humanos
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1414-1419, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295260

RESUMO

OBJECTIVE: To analyze the clinical efficacy and possible influencing factors of autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment of patients with multiple myeloma (MM). METHODS: Clinical data of 40 MM patients received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from September 2010 to November 2017 were retrospectively analyzed, the clinical curative efficiency was summarized and the related factors were analyzed. RESULTS: The curative efficiency of the patients before transplantation was 9(22.5%) with complete remission(CR), 5(12.5%) with very good partial remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them was PR after 3 recurrences. The curative efficiency after transplantation was 22(55%) with complete remission(CR), 12(30%) with very good partial remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88) months,15 cases presented disease progression, 7 cases were dead, 3-year estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1% and 82% respectively. Unvariate analysis showed that the OS was affected by ISS stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by ISS stage (P<0.01), before transplantation induction therapy (27 cases with bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed that the independent prognostic factors for OS were ISS stage, CR and VGPR after transplantation; the independent prognostic factors for PFS were the CR, VGPR, ISS stage after transplantation and induction therapy before transplant. CONCLUSION: Auto-HSCT can improve the clinical efficacy and survival rate of MM patients; ISS stage, CR and VGPR after transplantation are independent prognostic factors for OS and PFS, and induction therapy before transplantation is also an independent prognostic factor for PFS.


Assuntos
Mieloma Múltiplo , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Humanos , Mieloma Múltiplo/terapia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo
19.
Clin Exp Pharmacol Physiol ; 45(12): 1325-1327, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30075047

RESUMO

Recombinant human endostatin (rhES) can inhibit multiple myeloma, while its clinical efficacy in treating relapsed refractory multiple myeloma (RRMM) has not been assessed. One hundred and eleven RRMM patients were treated with four different regimens: combination of VD (velcade+dexamethasone) and rhES (n = 25), Thalidomide (Tha) and VD (VTD, n = 22) combination, rhES and conventional chemotherapy combination (n = 32), and combination of conventional chemotherapy and Tha (n = 32). Significant differences were found in progression-free survival (PFS) between rhES combination groups and conventional chemotherapy combination groups. No statistical difference was found in overall response rate, overall survival or incidences of adverse effects. The combination of rhES with VD or conventional chemotherapy is active in patients with RRMM and prolongs the PFS to improve the quality of life.


Assuntos
Endostatinas/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Proteínas Recombinantes/farmacologia , Intervalo Livre de Doença , Endostatinas/uso terapêutico , Humanos , Proteínas Recombinantes/uso terapêutico , Recidiva , Falha de Tratamento
20.
Medicine (Baltimore) ; 96(1): e5787, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28072730

RESUMO

BACKGROUND: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. CASE SUMMARY: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra. The patient was diagnosed with MM upon examination. A chest computed tomography (CT) scan revealed a round mass in the left lower lobe of the lungs, and a CT-guided needle biopsy uncovered a moderately differentiated adenocarcinoma. There were no additional notable findings in the left lung using positron emission tomography computed tomography (PET-CT). Therefore, a diagnosis of MM with pulmonary adenocarcinoma was made. Surgery was performed to excise the lung cancer. Bortezomib was used as first-line induction therapy against both tumors and lenalidomide was used for maintenance. The patient went into complete remission. Using this combined chemotherapy, the patient has survived for over 3 years since a diagnosis was made despite relapsing twice after the first year. CONCLUSION: This report clearly delineates the diagnosis and treatment of a rare case of synchronous MM and pulmonary adenocarcinoma, as well as depicts a potentially positive outcome for the patient. It also overviews some diagnostic and therapeutic implications for clinicians.


Assuntos
Adenocarcinoma , Bortezomib/administração & dosagem , Neoplasias Pulmonares , Pulmão , Mieloma Múltiplo , Talidomida/análogos & derivados , Vértebras Torácicas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia por Agulha/métodos , Humanos , Lenalidomida , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Imageamento por Ressonância Magnética/métodos , Masculino , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Neoplasias Primárias Múltiplas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Talidomida/administração & dosagem , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/patologia , Resultado do Tratamento
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