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OBJECTIVE: To explore the role of bone marrow mesenchymal stem cells (BMSC)ï¼an essential element of the bone marrow microenvironment, in multidrug resistance(MDR) of K562 cells, as well as the reversal effect of tetrandrine (TET) on BMSC-mediated MDR and its potential mechanism. METHODS: A mixed co-culture system and a transwell co-culture system for BMSC and K562 cells were established, and the cells were divided into different groups and treated with daunorubicin (DNR) alone or combined with TET and DNR. The CCK-8 assay was used to detect the proliferation of K562 cells in each group, and the cell inhibition rate was calculated. Cytometric bead array (CBA) was used to detect the expression levels of IFN, IL-2, IL-6 and IL-10 in the supernatant of different groups. RT-qPCR and Western blot were used to detected the expression of STAT3 at mRNA and protein levels, respectively. RESULTS: Compared with K562+DNR group, the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR group was significantly decreased (P < 0.05), while the levels of IL-6 in the culture supernatant and phosphorylated STAT3 in K562 cells were significantly increased (P < 0.05). Compared with K562+BMSC+DNR group, the inhibition rate of DNR on K562 cell proliferation in K562+BMSC+DNR+TET group was significantly increased (P < 0.05), while the level of IL-6 and phosphorylated STAT3 was significantly decreased (P < 0.05). CONCLUSION: BMSC can promote the drug resistance of leukemia cells, and TET may reverse the BMSC-mediated drug resistance via inhibiting IL-6/STAT3 signaling pathway.
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Bencilisoquinolinas , Leucemia , Humanos , Interleucina-6 , Resistencia a Antineoplásicos , Bencilisoquinolinas/farmacología , Bencilisoquinolinas/uso terapéutico , Daunorrubicina/farmacología , Células K562 , Leucemia/tratamiento farmacológico , Microambiente TumoralRESUMEN
BACKGROUND: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, exhibiting a more unfavorable prognosis than multiple myeloma. PCL is classified into pPCL and sPCL. Recently, the IMWG has recommended new PCL definition criteria, which require the presence of ≥5% circulating plasma cells in peripheral blood smears. Due to its low incidence, research on pPCL and sPCL is limited. METHODS: We conducted a retrospective study and analyzed clinical and cytogenetic data of pPCL and sPCL patients. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method, and survival distributions were compared using the log-rank test. RESULTS: This is a small cohort comprising 23 pPCL and 9 sPCL patients. Notably, sPCL patients showed a higher incidence of extramedullary infiltration and a higher percentage of bone marrow plasma cells (p = 0.015 and 0.025, respectively). Although no significant difference was found between the two groups in OS and PFS, a trend emerged suggesting a superior survival outcome for pPCL patients, with a higher cumulative 1-year PFS rate (38.3% vs. 13.3%) and a lower early mortality rate (mortality rate at 3 months: 15% vs. 33%). We also suggested that pPCL patients carrying t(11;14) may have a longer median survival time than individuals with other cytogenetic abnormalities, but this was not confirmed due to the small sample size. CONCLUSION: Our study revealed clinical and cytogenetic features of pPCL and sPCL patients according to the new diagnostic criteria. The findings suggested a generally better prognosis for pPCL than sPCL and the likelihood of t(11;14) translocation acting as a favorable prognostic factor in pPCL. It is important to note that our study had a limited sample size, which may lead to bias. We hope well-designed studies can be conducted to provide more results.
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Leucemia de Células Plasmáticas , Mieloma Múltiple , Humanos , Leucemia de Células Plasmáticas/diagnóstico , Leucemia de Células Plasmáticas/genética , Estudios Retrospectivos , Citogenética , Análisis CitogenéticoRESUMEN
OBJECTIVE: To investigate the therapeutic effect of targeted drug-loaded nanoparticles modified by transferrin receptor monoclonal antibody (TfR mAb) on acute leukemia and its potential anti-tumor mechanism. METHODS: Nanoparticles drug delivery system, which was composed of poly (lactic-co-glycolic acid), poly-l-lysine, polyethylene glycol, TfR mAb (TfR mAb-PLGA-PLL-PEG)-daunorubicin (DNR), was first synthesized. After drug intervention, the intracellular accumulation in leukemia HL60 cells was observed under a fluorescent microscope and concentration of DNR was determined by flow cytometry (FCM). Meanwhile, cell apoptosis rate was measured by FCM and the expression levels of apoptosis related protein Cleaved-caspase 3 was determined by Western blot. RESULTS: Under an inverted fluorescent microscope, intracellular accumulation of DNR autofluorescence in HL60 cells was observed in both TfR mAb-PLGA-PLL-PEG-DNR group and DNR group. FCM analysis showed that the intracellular concentration of DNR in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that in DNR groupï¼P<0.05ï¼. The apoptotic rate of HL60 cells in TfR mAb-PLGA-PLL-PEG-DNR group was higher than that of DNR groupï¼P<0.05ï¼. Moreover, the expression levels of apoptosis-related protein Cleaved-caspase 3 in TfR mAb-PLGA-PLL-PEG-DNR group was significantly higher than that in DNR groupï¼P<0.05ï¼. CONCLUSION: TfR mAb-PLGA-PLL-PEG nanoparticle drug delivery system can target chemotherapy drugs to leukemia cells and enhance anticancer ability through apoptotic pathway.
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OBJECTIVE: This study explored the relationship between the activation of the jak/stat3 signaling pathway and the CSN5 gene transcript and protein expression levels in the hematopoietic stem cells of patients with myelodysplastic syndromes (MDSs). This study also aimed to investigate the correlation between the expression level of CSN5 and the deubiquitination of HSF1, as well as the transcript level of the spi1/pu.1 genes to explore the pathogenesis of MDS. MATERIALS AND METHODS: We isolated cells from normal individuals and MDS patients, and the mRNA and protein expression levels of spi1/pu.1 in cd34+ cells (hematopoietic stem cells) were measured by PCR and western blotting, respectively. A ChIP assay was used to detect the binding of HSF1 to the spi1/pu.1 promoter in cd34+ cells. The ubiquitination of HSF1 in cd34+ cells was detected by CO-IP. The binding of HSF1 and Fbxw7α was detected in in cd34+ cells by CO-IP. The binding of HSF1 and CSN5 was evaluated. A luciferase reporter assay was used to detect the effect of STAT3 on CSN5 promoter activation in cd34+ cells. Western blotting was used to detect the phosphorylation of STAT3 in cd34+ cells of MDS patients. The binding of STAT3 and C/EBP beta in cd34+ cells was detected by CO-IP. RESULTS: Inhibition of SPI1/PU.1 expression was observed in MDS samples with low proliferation ability. Further experiments proved that phosphorylation of STAT3 affected CSN5 function and mediated the ubiquitination of HSF, the upstream regulator of SPI1/PU.1 transcription, which led to the inhibition of SPI1/PU.1 expression. Restoration of CSN5 rescued the inhibition of HSF1 ubiquitination, causing SPI1/PU.1 transcription to resume and increasing SPI1/PU.1 expression, promoting the recovery of cell proliferation in hypocellular MDS. CONCLUSIONS: Our research revealed the regulatory role of the CSN5/HSF/SPI1/PU.1 axis in hypocellular MDS, providing a probable target for clinical intervention.
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Myelodysplastic syndromes (MDS) refer to a set of clonal hematopoietic disorders with fusion transcript as disease progression. Breakpoint cluster region/abelson (BCR::ABL) fusion mostly occurs during the progressive phase from MDS to higher stages and acute leukemia transformation. Besides, it is extremely rare reported on the diagnosis of MDS. Here, the first case of transformation of de nove philadelphia (Ph)-positive MDS to chronic myeloid leukemia (CML) with rapid progression to acute myeloid leukemia (AML) was reported. Fluorescence in situ hybridization (FISH) analysis revealed an atypical BCR::ABL positive signal (2R2G1Y) that accounted for 3% at the diagnosis of MDS and increased to 21.4% at information to CML. The result of multiplex reverse transcriptase polymerase chain reaction (RT-PCR) indicated a rearrangement of e19a2 (p230 BCR::ABL). The treatment with 400 mg of imatinib daily at the transformation from MDS to CML led to a hematological response. However, the patient stopped taking imatinib due to the worsening of cytopenias after five weeks of therapy and rapid progression to AML in another two months. The treatment with azacitidine (AZA) and venetoclax (VEN) achieved partial remission (PR). Unfortunately, the patient relapsed six months after PR and died shortly thereafter. In addition, another 16 cases of adult cases that reported MDS with de nove Ph-positive were also reviewed to learn about clinical features and outcomes.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Humanos , Cromosoma Filadelfia , Mesilato de Imatinib/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/genética , Transformación Celular Neoplásica , CariotipoRESUMEN
Although studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated risk of lymphoma with different SPMs and risk factors related to different SPMs. We conducted a retrospective cohort study to evaluate the cumulative incidence and risk factors of different secondary SPMs in patients previously diagnosed as lymphoma, and to compare the survival rates of SPMs and primary malignant tumors. Retrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results database. Patients with an initial primary malignancy diagnosis of lymphoma between 2000 and 2019 were included in the study. The statistical analysis was conducted from March 2022 to January 2023. The development of an SPM defined as any type of malignant tumor 292,210 patients remained in final cohort, including 35,220 patients with secondary primary malignant tumor. The cumulative incidence of SPMs during 20 years of follow-up is 1.95% in combined respiratory system, 0.14% in central nervous system, is 0.82% hepatobiliary pancreatic system, is 1.31% in urinary system, is 1.92% digestive tract. Multivariate competitive risk model analysis showed that Different characteristics of lymphoma patients were associated with secondary different types of SPMS. The risk of secondary SPMs in lymphoma patients after radiotherapy and chemotherapy varies with the change of diagnosis time, diagnosis age and incubation period. Propensity score matching and Kaplan-Meier analysis showed that the survival rate of secondary tumor was significantly lower than that of matched primary malignant tumor. This study reminds us to consider the possibility of SPMs in the initial treatment of lymphoma patients, and develop a follow-up plan according to the characteristics of patients to reduce the risk of SPMs. Occurring more than 6 months after the diagnosis of lymphoma. The cumulative incidence of SPMs was estimated by Fine-Gray competing risk regression. Poisson regression was used to evaluate the therapeutic factors associated risk for SPMs in patients undergoing radiotherapy or chemotherapy. The Kaplan-Meier method was used to assess the survival outcomes of patients with SPMs.
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Linfoma , Neoplasias Primarias Secundarias , Humanos , Neoplasias Primarias Secundarias/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Linfoma/epidemiología , Linfoma/terapia , Linfoma/complicaciones , IncidenciaRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL). 30 ~ 40% of DLBCL patients were resistant to the standard R-CHOP regimen or recurrence after remission. It is currently believed that drug resistance is the main cause of the recurrence and refractory of DLBCL (R/R DLBCL). With the increased understanding of DLBCL biology, tumor microenvironment and epigenetics, some new therapies and drugs like molecular and signal pathway target therapy, chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, antibody drug-conjugate and tafasitamab have been used for R/R DLBCL. This article will review the drug resistance mechanism and novel targeted drugs and therapies of DLBCL.
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Hematologic malignancies (HMs) mainly include acute and chronic leukemia, lymphoma, myeloma and other heterogeneous tumors that seriously threaten human life and health. The common effective treatments are radiotherapy, chemotherapy and hematopoietic stem cell transplantation (HSCT), which have limited options and are prone to tumor recurrence and (or) drug resistance. Metformin is the first-line drug for the treatment of type 2 diabetes (T2DM). Recently, studies identified the potential anti-cancer ability of metformin in both T2DM patients and patients that are non-diabetic. The latest epidemiological and preclinical studies suggested a potential benefit of metformin in the prevention and treatment of patients with HM. The mechanism may involve the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway by metformin as well as other AMPK-independent pathways to exert anti-cancer properties. In addition, combining current conventional anti-cancer drugs with metformin may improve the efficacy and reduce adverse drug reactions. Therefore, metformin can also be used as an adjuvant therapeutic agent for HM. This paper highlights the anti-hyperglycemic effects and potential anti-cancer effects of metformin, and also compiles the in vitro and clinical trials of metformin as an anti-cancer and chemosensitizing agent for the treatment of HM. The need for future research on the use of metformin in the treatment of HM is indicated.
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Diabetes Mellitus Tipo 2 , Neoplasias Hematológicas , Metformina , Neoplasias , Humanos , Metformina/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neoplasias/tratamiento farmacológicoRESUMEN
Recent studies have shown human platelets can access the tumor microenvironment by passive diffusion across capillaries or via activated immune cells. In a previous study, we exploited this affinity of platelets for tumor cells as part of a new approach to target tumors with modified platelets. Therefore, the engineering of human nanoplatelets as living vehicles for in vivo tumor-targeted near-infra-red fluorescence (NIRF) imaging and the delivery of cytotoxins to tumor cells by endocytosis are described in this study. Nanoplatelets with an average diameter of 200 nm were prepared by mild sonication of kabiramide C (KabC)-loaded human platelets. The sealed plasma membrane of the nanoplatelets allows them to accumulate and retain membrane-permeable chemicals, such as epidoxorubicin (EPI) and KabC. Tumor-targeted imaging functionalities were engineered on the nanoplatelets by surface-coupling transferrin, Cy5 and Cy7. High-resolution fluorescence imaging and flow cytometry analyses showed that the nanoplatelets loaded with EPI and Cy5 targeted human myeloma cells (RPMI8226 cells) that over-expressed the transferrin receptor. The endocytosis of the nanoplatelets by RPMI8226 cells was transferrin-dependent and induced apoptosis. The test results also showed that the nanoplatelets functionalized with transferrin and Cy7 and injected in mice bearing RPMI8226 cells-derived myeloma xenotransplants accumulated in the tumor tissue and could be used for high-contrast in vivo NIRF imaging of early-stage tumors. Nanoplatelets represent a new class of living nano-vehicles that may efficiently target and deliver therapeutic agents and imaging probes to diseased tissues including tumors.
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Lung cancer remains the leading cause of cancer deaths. Non-small cell lung cancer (NSCLC) is the most frequent subtype of lung cancer. Surgery, radiation, chemotherapy, immunotherapy, or molecularly targeted therapy is used to treat NSCLC. Nevertheless, many patients who accept surgery likely develop distant metastases or local recurrence. In recent years, targeted treatments and immunotherapy have achieved improvement at a breakneck pace. Therapy must be customized for each patient based on the specific medical condition, as well as other variables. It is critical to have an accurate NSCLC sub-classification for tailored treatment, according to the latest World Health Organization standards.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/patología , Terapia Combinada , Inmunoterapia , Factores de RiesgoRESUMEN
BACKGROUND: Refractory abdominal wounds are commonly complicated by surgical site infections, which prolong hospital stays and increase medical costs. There is little clinical data on the use of allogeneic platelet gel (PG) therapy for refractory infected wounds. OBJECTIVES: This study aimed to evaluate the efficacy and safety of allogeneic PGs in the treatment of refractory abdominal wounds. MATERIAL AND METHODS: A prospective single-center study was performed in a national abdominal trauma referral center between June 2019 and June 2021. A total of 11 patients with refractory abdominal wounds were treated with allogeneic PGs after the failure of standard medical treatments. The PGs were derived from platelets collected from healthy donors using apheresis, and each PG was tested for platelet count, transfusion-related diseases, aerobic and anaerobic bacteria, and growth factor concentration. Clinical efficacy was evaluated by assessing the wound surface and observing the condition of the wound, including wound area and percentage of granulation. RESULTS: The median age of the patients was 37 years (1st quartile, 3rd quartile (Q1, Q3): 31-55 years), median (Q1, Q3) hemoglobin level was 95 g/L (78-120 g/L) and median (Q1, Q3) serum albumin level was 39.9 g/L (34.9-42.7 g/L). The PG platelet count was 976.5 ±174.9×109/L. Results of transfusion-associated contagion tests for aerobic and anaerobic bacteria were negative. Growth factor contents (pg/mL) were: for transforming growth factor beta 1 (TGF-ß1); 2542.39 ±430.60, for platelet-derived growth factor BB (PDGF-BB); 23230.03 ±4236.14 and FOR vascular endothelial growth factor (VEGF); 91.41 ±23.31. The rate of wound healing was 100%, and the median (Q1, Q3) healing time was 30 days (18-40 days). The follow-up period was 5-27 months, during which no recurrence of the wounds was found. CONCLUSIONS: The present study demonstrated that allogeneic PGs are a safe and effective treatment for refractory abdominal wounds.
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Plaquetas , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Factor A de Crecimiento Endotelial Vascular , Estudios Prospectivos , Cicatrización de HeridasRESUMEN
Hepatocyte growth factor receptor (HGFR or Met) upregulation has been proven to play important roles in non-small cell lung carcinoma (NSCLC). Interestingly, chemoresistance against epidermal growth factor receptor (EGFR) inhibitors including erlotinib and gefitinib was also related to Met. Targeting bromodomain and extra terminal domain (BET) proteins, especially BRD4, has shown inhibitory effects on lung cancer, but the mechanism is unclear. Herein, we found that JQ1 (BET inhibitor) suppressed NSCLC cell growth, reduced the Met expression, and contributed to inactivation of PI3K/Akt and MAPK/ERK pathways. Moreover, another BET protein inhibitor I-BET151, or BRD4 depletion, also inhibited NSCLC cell growth and downregulated Met. JQ1 inhibited HGF-induced cell growth and Met/PI3K/Akt activation, also inhibited A549 tumor growth in xenograft mouse models, in parallel with Met downregulation. Moreover, JQ1 inhibited the growth of paired erlotinib-sensitive and resistant HCC827 cells in parallel with Met downregulation and PI3K/Akt signaling inactivation. JQ1 also exerted inhibitory influences on the growth of erlotinib-sensitive and resistant HCC827 tumors in xenograft mouse models. These results suggested that targeting BET proteins inhibited NSCLC via downregulating Met and inactivating PI3K/AKT pathway. Our findings reveal a novel mechanism of BET proteins implicated in NSCLC progression with Met taken into consideration.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Clorhidrato de Erlotinib/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Nucleares/metabolismo , Regulación hacia Abajo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Factores de Transcripción/metabolismo , Neoplasias Pulmonares/patología , Proliferación Celular , Resistencia a Antineoplásicos , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Ciclo Celular/metabolismoRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are enriched in exosomes and are extremely stable. Exosome-mediated intercellular transfer of specific biologically active circRNA molecules can drive the transformation of the tumor microenvironment and accelerate or inhibit the local spread and multifocal growth of hepatocellular carcinoma (HCC). In this study, we explored in depth about the biological roles of HCC cell-derived exosomes and exosome-transported circRNAs on HCC in vivo and in vitro. METHODS: Exosomes extracted from HCC cells (Huh7 and HA22T) were characterized using transmission electron microscopy, nanoparticle size tracer analysis, and western blotting. Exosomes were observed for endocytosis using fluorescent labeling. The effects of HCC cell-derived exosomes and the circ_002136 they carried on cell growth, metastasis and apoptosis were determined by CCK-8 assay, transwell assay, flow cytometry analysis and TUNEL staining, respectively. The expressions of circ_002136, miR-19a-3p and RAB1A were detected by quantitative RT-PCR (qRT-PCR). Targeted binding between miR-19a-3p and circ_002136 or RAB1A was predicted and verified by bioinformatics analysis, dual-luciferase reporter and RNA pull-down experiments. The in vivo effect of circ_002136 was determined by constructing a xenograft tumor model. RESULTS: The findings revealed that Huh7 and HA22T exosomes conferred enhanced viability as well as invasive ability to recipient HCC cells. Circ_002136 was shown for the first time to be differentially upregulated in HCC tissues and cells and transferred by HCC cell-derived exosomes. More importantly, selective silencing of circ_002136 depleted the malignant biological behaviors of HCC exosome-activated Huh7 and HA22T cells. Depletion of circ_002136 in vivo effectively retarded the growth of HCC xenograft tumors. Furthermore, a well-established circ_002136 ceRNA regulatory network was constructed, namely circ_002136 blocked miR-19a-3p expression, elevated RAB1A expression activity and stimulated HCC development. Finally, high levels of circ_002136 or RAB1A, as well as low levels of miR-19a-3p, negatively affected HCC patient survival. CONCLUSION: The study on circ_002136 provides good data to support our insight into the mechanism of to-be-silenced circRNA as a therapeutic agent in the progression of HCC.
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Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Exosomas/genética , ARN Circular/genética , MicroARNs/genética , Microambiente TumoralRESUMEN
BACKGROUND: Immunotherapy with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been widely used in the treatment of solid tumors and Hodgkin lymphoma, demonstrating powerful efficacy and good safety. However, there is no systematic review and meta-analysis to fully investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treating non-Hodgkin lymphoma (NHL). METHODS: We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and abstracts of conference proceedings of annual meetings up to January 23, 2022, to identify eligible clinical trials. To evaluate the efficacy of PD-1/PD-L1 inhibitors, objective response rate (ORR), complete response rate (CRR), 1-year overall survival rate, and 1-year progression-free survival rate were analyzed. For safety analysis, we calculated rates of any grade and grade ≥3 treatment-related adverse events. RESULTS: Overall 22 studies and 1150 participants were enrolled in this meta-analysis. The pooled ORR, CRR, 1-year overall survival, and 1-year progression-free survival rates were 0.43 (95% confidence interval [CI], 0.33-0.54), 0.21 (95% CI, 0.13-0.31), 0.72 (95% CI, 0.58-0.89), and 0.42 (95% CI, 0.29-0.62), respectively. The ORR and CRR in the combination immunochemotherapy subgroup (0.65 and 0.41) were higher than those in the monotherapy (0.27 and 0.09) and combination chemotherapy (0.39 and 0.19) subgroups. This study was registered with PROSPERO (#CRD 42022316805). CONCLUSION: Given that there were limited clinical trials and relatively few relevant studies, we conducted this meta-analysis to fully elucidate the efficacy and safety of PD-1/PD-L1 inhibitors in NHL. Our results suggested that PD-1/PD-L1 inhibitors improved outcomes of responses as well as survival rates in NHL patients with tolerable adverse events. More well-designed randomized clinical trials are still needed to further confirm our findings.
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Enfermedad de Hodgkin , Neoplasias Pulmonares , Linfoma no Hodgkin , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Antígeno B7-H1/uso terapéutico , Receptor de Muerte Celular Programada 1 , Linfoma no Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/tratamiento farmacológico , Apoptosis , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
The gene changes for diagnosis and prognosis of diffuse large B cell lymphoma (DLBCL) still remain unclear. RAC1 was reported to be asso;ciated with the B cell receptor signal pathway, but its relations with DLBCL have not yet been systematically explored. In this study, we have conducted molecular, bioinformatics and clinical analyses by using publicly available data from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test and logistic regression were performed to evaluate the association between RAC1 and clinical features in patients. Kaplan-Meier and Cox regression methods were used to examine the impacts of RAC1 expression level on overall survival, and a nomogram was performed to illustrate the correlation between RAC1 and the risk of DLBCL. Our results revealed that the expression level of RAC1 in DLBCL was higher than that in normal tissues or lymphadenitis. High-level expression of RAC1 was significantly associated with clinical stage, as well as being an independent factor affecting overall survival. RAC1 was negatively correlated with Bruton's tyrosine kinase (BTK). The association between RAC1 gene expression and the risk of DLBCL was presented in a nomogram. In conclusion, RAC1 expression patterns may be used to predict the development and prognosis of DLBCL.
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Linfoma de Células B Grandes Difuso , Humanos , Pronóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Receptores de Antígenos de Linfocitos B/metabolismo , Proteína de Unión al GTP rac1/genética , Proteína de Unión al GTP rac1/metabolismoRESUMEN
Background: Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously. Methods: Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG). Results: GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O2) in the tumor were converted to H2O2 under the catalysis of GOx. HMMD can catalyze H2O2 to produce O2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO2 release was accelerated from the nanoparticles after the "gatekeeper" MnO2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs. Conclusion: This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage.
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Nanopartículas , Neoplasias , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Glucosa Oxidasa/metabolismo , Humanos , Peróxido de Hidrógeno , Compuestos de Manganeso , Nanopartículas/uso terapéutico , Nanotecnología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Óxidos , Sulfuros/farmacología , Microambiente TumoralRESUMEN
BACKGROUND: Conversion therapy has been widely applied in various cancer types including intrahepatic cholangiocarcinoma (ICC). The aim of this retrospective study was to evaluate the efficacy and safety of transarterial chemoembolization combined with lenvatinib (TACE-L) as a novel conversion therapy in patients with initially unresectable ICC. METHODS: Enrolled in this retrospective study were patients with unresectable ICC who received TACE-L between January 2015 and May 2018. The patients were evaluated every 2 months for possible secondary resection. RESULTS: Of the 44 eligible patients, 28 (63.6%) were successfully downstaged to receive surgical resection and the other 16 patients were included into the unsuccessfully downstaged group. The overall adverse events during TACE-L were moderate, including 12 patients (27.3%) with Grade 3 or 4 toxicities. Of the 28 downregulated patients, 23 (82.1%) achieved an R0 resection, and 6 (21.4%) had Clavien-Dindo grade ≥ 3 complications, including one postoperative death. Kaplan-Meier curves showed that the successfully downstaged patients had better overall survival (OS) than the unsuccessfully downstaged patients (P = 0.006). Multivariable analysis identified successful TACE-L conversion therapy as a significantly favorable prognostic factor for OS. CONCLUSIONS: TACE-L proves to be a safe and efficacious conversion therapy modality that allows for secondary resectability in patients with initially unresectable ICC.
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Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Colangiocarcinoma , Neoplasias Hepáticas , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos/patología , Quimioembolización Terapéutica/efectos adversos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/cirugía , Humanos , Neoplasias Hepáticas/patología , Compuestos de Fenilurea , Quinolinas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: This review aims to see the progress of several clinically-used monoclonal antibodies in treating ALL patients and how they improved patients' outcomes. METHODS: We searched Web of Science, Elsevier and PubMed for relevant published studies, and summarized eligible evidence on the management of newly-diagnosed and relapsed or refractory ALL with monoclonal antibodies. Ongoing trials were identified from ClinicalTrials.gov. RESULTS: Rituximab, an anti-CD20 monoclonal antibody, prolonged patients' complete remission duration and overall survival when combined with hyper-CVAD regimen. Another anti-CD20 monoclonal antibody, Ofatumumab, was reported to have similar benefits. Blinatumomab allows endogenous CD3-positive cytotoxic T cells to target and eliminate CD19-positive blasts. FDA has approved its efficacy in patients with R/R B-ALL and eliminating minimal residual disease (MRD). It serves as a bridge to eradicate MRD before transplantation, and may also be a new choice for patients unable to undergo transplantation. An anti-CD22 monoclonal antibody named Inotuzumab Ozogamicin showed great improvement in patients' outcome, but its toxicity to liver is also worthy of our attention. CONCLUSION: Monoclonal antibodies are proven to be a promising immunotherapeutic strategy to improve ALL patients' outcome in the long term. There's still a need for individualized treatment with effective and well-tolerated medicines.Trial registration: ClinicalTrials.gov identifier: NCT01363128.Trial registration: ClinicalTrials.gov identifier: NCT01466179.Trial registration: ClinicalTrials.gov identifier: NCT02013167.Trial registration: ClinicalTrials.gov identifier: NCT02000427.Trial registration: ClinicalTrials.gov identifier: NCT01564784.Trial registration: ClinicalTrials.gov identifier: NCT03677596.Trial registration: ClinicalTrials.gov identifier: NCT01363297.Trial registration: ClinicalTrials.gov identifier: NCT02981628.Trial registration: ClinicalTrials.gov identifier: NCT03094611.Trial registration: ClinicalTrials.gov identifier: NCT01371630.Trial registration: ClinicalTrials.gov identifier: NCT04224571.Trial registration: ClinicalTrials.gov identifier: NCT02458014.Trial registration: ClinicalTrials.gov identifier: NCT04546399.Trial registration: ClinicalTrials.gov identifier: NCT02879695.Trial registration: ClinicalTrials.gov identifier: NCT03913559.Trial registration: ClinicalTrials.gov identifier: NCT03441061.Trial registration: ClinicalTrials.gov identifier: NCT03739814.Trial registration: ClinicalTrials.gov identifier: NCT02877303.Trial registration: ClinicalTrials.gov identifier: NCT03698552.Trial registration: ClinicalTrials.gov identifier: NCT04601584.Trial registration: ClinicalTrials.gov identifier: NCT04684147.Trial registration: ClinicalTrials.gov identifier: NCT04681105.
Asunto(s)
Antineoplásicos Inmunológicos , Antineoplásicos , Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Humanos , Inotuzumab Ozogamicina , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Patients with primary cancer receiving chemotherapy and/or radiotherapy may develop therapy-related acute leukemia (t-AL). Therapy-related acute myeloid leukemia (t-AML) accounts for the majority of these cases and is frequently associated with a variety of cytogenetic and molecular abnormalities. The aim of the present study was to explore the clinical characteristics, treatments and prognosis of patients with t-AML. A total of 272 cases of AML treated at our institution between 2016 and 2020 were reviewed, among which nine cases of t-AML were identified for analysis. All patients had received alkylating or topoisomerase II inhibitor chemotherapy drugs for primary cancer treatment and three patients had received radiotherapy. A total of nine patients had been administered recombinant human granulocyte colony-stimulating factor (G-CSF). The median latency period for the nine patients with t-AML was 25 months (range, 10-240 months). The molecular cytogenetic abnormalities included t(15:17)(q22:q21), inv(16)(p13q22), del(5)(q22), CBFB/MYH11(+), FLT3(+), NARS(+), IDH(+), TET2(+), and TP53(+). Out of nine patients with t-AML, eight received chemotherapy, two of whom underwent HSCT. The median survival time of the nine patients with t-AML was 10 months and the 2-year-survival rate was 44.4%. Greater clarity around the diagnosis and treatment is required to improve the outcomes of patients with t-AML.