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1.
Cancer Med ; 13(13): e7409, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38967515

ABSTRACT

AIM: This study aimed to explore the association between patient-reported items at different time points after hematopoietic stem cell transplantation (HSCT) and long-term survival. METHODS: We conducted a study with 144 allogeneic HSCT patients, following them for 5 years post-transplantation. Data from the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire were collected before transplantation and at 1, 3, 6, 12, 18, 36, and 60 months after transplantation. Demographic characteristics and survival status were also assessed. RESULTS: Among the 144 cases, the 5-year overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and graft-versus-host disease-free (GRFS) rates were 65%, 48%, 17%, and 36% respectively. Health-related quality of life (HRQOL) showed a fluctuating pattern over 5 years. Using a latent class mixed model, patients were classified into two groups based on their physical well-being (PWB) scores during the 60-month follow-up. Class 1 had initially lower PWB scores, which gradually increased over time. In contrast, Class 2 maintained higher PWB scores with slight increases over time. Kaplan-Meier survival analysis revealed that Class 1 had better OS (70.9% vs. 52.9%, p = 0.021), PFS (60.5% vs. 41.2%, p = 0.039), and GRFS (35.1% vs. 29.3%, p = 0.035) compared to Class 2. CONCLUSIONS: Patients who had higher initial PWB scores after HSCT demonstrated improved long-term survival outcomes. The PWB score could serve as a valuable predictor for the prognosis of HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Patient Reported Outcome Measures , Quality of Life , Humans , Male , Female , Adult , Middle Aged , Young Adult , Graft vs Host Disease/etiology , Adolescent , Surveys and Questionnaires
2.
Asia Pac J Oncol Nurs ; 11(3): 100368, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38426045

ABSTRACT

Effectively addressing the challenges posed by relapsed and refractory diffuse large B-cell lymphoma, particularly when employing autologous hematopoietic stem cell transplantation and CAR-T therapy, requires a comprehensive approach to treatment and nursing. This case report emphasizes a nursing strategy focused on managing neurotoxicity post-CAR-T therapy. Nursing interventions include the identification of neurotoxicity symptoms, neuropsychiatric management, careful support during lumbar puncture and intrathecal administration, psychological assistance, and adaptive nutritional guidance. The diligent application of treatment and nursing care resulted in a remarkable recovery for the patient, as evidenced by the alleviation of central facial paralysis, improvement in swallowing function (from Grade 4 to Grade 2), and enhanced vocalization. Consistent and specialized nursing care is paramount for effectively managing complications, especially neurotoxicity, in patients undergoing CAR-T therapy. A thorough monitoring of symptoms and personalized care contribute to optimizing treatment outcomes and ensuring patient safety.

4.
Br J Haematol ; 204(4): 1219-1226, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38180132

ABSTRACT

Venetoclax (VEN) in combination with hypomethylating agents (HMAs) is considered the standard of treatment for individuals with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. We conducted a retrospective analysis that encompassed 16 critically ill patients newly diagnosed with AML who were admitted to the intensive care unit (ICU) and received the VEN and HMA regimen. Among them, 13 were primary AML, and three were MDS-transformed AML. The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 18.9, and the mean sepsis-related organ failure assessment score (SOFA) was 6.2. The average length of the ICU stay was 27.3 days. The median duration of VEN administration was 16 days. After the first course of VEN + HMA, 12 cases (75%) achieved complete remission (CR) or CR with incomplete haematological recovery (CRi). Among the five patients harbouring TP53 mutations, the overall response rate (ORR) was 90%. All patients experienced grade 3-4 haematological adverse events (AEs). With a median follow-up of 9.5 months (range: 0.5-23), the overall survival (OS) rate was 43.75%. TP53-wild patients and CR state after the first course of VEN-HMA indicated better survival. The combination of VEN and HMA has demonstrated a significantly elevated therapeutic response rate in newly diagnosed AML patients with critical illness.


Subject(s)
Critical Illness , Leukemia, Myeloid, Acute , Sulfonamides , Humans , Retrospective Studies , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Leukemia, Myeloid, Acute/genetics , Pathologic Complete Response , Antineoplastic Combined Chemotherapy Protocols/adverse effects
6.
Nat Commun ; 14(1): 3642, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37339964

ABSTRACT

BCMA-targeting chimeric antigen receptor (CAR) T cell therapy demonstrates impressive clinical response in multiple myeloma (MM). However, some patients with BCMA-deficient tumours cannot benefit from this therapy, and others can experience BCMA antigen loss leading to relapse, thus necessitating the identification of additional CAR-T targets. Here, we show that FcRH5 is expressed on multiple myeloma cells and can be targeted with CAR-T cells. FcRH5 CAR-T cells elicited antigen-specific activation, cytokine secretion and cytotoxicity against MM cells. Moreover, FcRH5 CAR-T cells exhibited robust tumoricidal efficacy in murine xenograft models, including one deficient in BCMA expression. We also show that different forms of soluble FcRH5 can interfere with the efficacy of FcRH5 CAR-T cells. Lastly, FcRH5/BCMA-bispecific CAR-T cells efficiently recognized MM cells expressing FcRH5 and/or BCMA and displayed improved efficacy, compared with mono-specific CAR-T cells in vivo. These findings suggest that targeting FcRH5 with CAR-T cells may represent a promising therapeutic avenue for MM.


Subject(s)
Multiple Myeloma , Receptors, Chimeric Antigen , Humans , Animals , Mice , Multiple Myeloma/pathology , B-Cell Maturation Antigen , Heterografts , Neoplasm Recurrence, Local/metabolism , T-Lymphocytes
7.
ACS Omega ; 8(9): 8846-8864, 2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36910932

ABSTRACT

In petroleum drilling, carbonate formations characterized by natural fractures can result in troublesome gas-liquid gravity displacement, which refers to the phenomenon that the drilling mud leakage and gas kick are simultaneously triggered. This work focuses on clarifying the mechanism of gas-liquid displacement in vertical fractures during the drilling of carbonate formations and investigating the characteristics of gas-liquid displacement under various conditions. First, the bottom hole pressure allowing for gas-liquid gravity displacement is analyzed, which determines the coexistence condition of leakage and kick in vertical fractures. Then, a theoretical model of gas-liquid displacement flow in a vertical fracture is established. To verify the reliability and accuracy of the model, the results of numerical simulation are compared with those of a visualization experiment. The development process and flow characteristics of gas-liquid displacement in the fracture under different conditions are numerically simulated. The effects of pressure difference, drilling mud property, and fracture geometry on the gas-liquid displacement rate are analyzed. It is found that the drilling mud leakage rate increases with the increase of fracture width, fracture height, and drilling mud density, while it decreases with the increase of pressure difference and fracture length. The gas invasion rate increases with the increase of fracture width, fracture height, and pressure difference, while it decreases with the increase of drilling mud density and fracture length. The equations for leakage rate and gas invasion rate are derived by the response surface method, and the methods for mitigating gas-liquid gravity displacement are discussed. It is expected that the present work provides a better understanding of the gas-liquid gravity displacement in carbonate formations.

8.
Front Immunol ; 13: 904693, 2022.
Article in English | MEDLINE | ID: mdl-35784355

ABSTRACT

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.


Subject(s)
Lymphoma, B-Cell , Neoplasms , Humans , Immunotherapy , Killer Cells, Natural , Lymphocyte Activation , Lymphoma, B-Cell/metabolism , Lymphoma, B-Cell/therapy
9.
J Clin Lab Anal ; 36(7): e24547, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35689538

ABSTRACT

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is becoming a curable disease with the introduction of therapeutic plasma exchange (TPE). However, cardiovascular complications remain essential causes of mortality in patients with refractory TTP, while the association of cardiac biomarkers with the prognosis of TTP warrants further investigation. METHODS: Patients admitted to the First Affiliated Hospital of Soochow University for refractory TTP from 2013 through 2020 were included in this retrospective study. Clinical characteristics were collected from electronic health records. Biomarker levels on admission and post TPE were recorded. Logistic regression was adopted to identify risk factors for mortality. RESULTS: A total of 78 patients with refractory TTP were included in this study. Twenty-one patients died during hospitalization, with a mortality rate of 26.9%. High-sensitivity cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ratios (AAR) were increased in deceased patients compared with the survival group. Multivariate analysis showed that AAR after TPE was associated with overall mortality (OR: 4.45, 95% CI 1.09-18.19). The areas under the receiver operator characteristic curve (AUC) of AAR, hs-cTnT, and NT-proBNP for the association with mortality were 0.814, 0.840, and 0.829, respectively. CONCLUSION: Higher post-TPE cardiac biomarker levels are associated with increased in-hospital mortality in patients with refractory TTP.


Subject(s)
Natriuretic Peptide, Brain , Purpura, Thrombotic Thrombocytopenic , Biomarkers , China/epidemiology , Humans , Peptide Fragments , Prognosis , Purpura, Thrombotic Thrombocytopenic/complications , Purpura, Thrombotic Thrombocytopenic/therapy , Retrospective Studies , Troponin T
10.
Oncol Rep ; 47(4)2022 04.
Article in English | MEDLINE | ID: mdl-35103292

ABSTRACT

Chidamide, a selective histone deacetylase inhibitor, has antitumour effects. 5­azacitidine (5­AZA), a hypomethylating agent, is effective in treating acute myeloid leukaemia (AML) and myelodysplastic syndrome. However, to the best of our knowledge, the effect of chidamide and 5­AZA on AML cell lines has not been fully investigated. In the present study, the antileukaemia activity of chidamide, alone and in combination with 5­AZA, was assessed on different subtypes of AML cell lines (M1­M5) and primary samples from several patients with AML in vitro. The results indicated that the proliferation of leukaemia cells was significantly and dose­dependently inhibited by chidamide and 5­AZA alone or in combination. The combination also had marked synergistic effects to induce apoptosis of AML cells. The apoptosis of leukaemia cells was induced via downregulation of BCL­2 and myeloid­cell leukemia 1 (MCL­1) levels. Of note, chidamide also degraded the MCL­1 protein in venetoclax­resistant U937 cells, in which the MCL­1 protein is upregulated. In addition, chidamide was able to induce myeloid differentiation (with CD11b upregulation) of AML cell lines or monocytic/dendritic differentiation (with CD86 upregulation) of primary cultured cells from several patients with AML. Chidamide was also able to promote the differentiation of the venetoclax­resistant U937 cell line by upregulating CD11b expression. In conclusion, chidamide alone or combined with 5­AZA may be an effective therapy for AML.


Subject(s)
Aminopyridines/pharmacology , Azacitidine/pharmacology , Benzamides/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Antimetabolites, Antineoplastic/therapeutic use , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation , Drug Synergism , Epigenomics , Humans , U937 Cells , Up-Regulation
11.
J Clin Lab Anal ; 35(12): e24100, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34762754

ABSTRACT

OBJECTIVES: This study aimed to explore clinical indexes for management of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia by comparing hematological and radiological characteristics. METHODS: Severe/critically ill patients with COVID-19, H7N9, and H1N1 pneumonia were retrospectively enrolled. The demographic data, clinical manifestations, hematological parameters, and radiological characteristics were compared. RESULTS: In this study, 16 cases of COVID-19, 10 cases of H7N9, and 13 cases of H1N1 who met severe/critically ill criteria were included. Compared with COVID-19, H7N9 and H1N1 groups had more chronic diseases (80% and 92.3% vs. 25%, p < 0.05), higher APACHE Ⅱ scores (16.00 ± 8.63 and 15.08 ± 6.24, vs. 5.50 ± 2.58, p < 0.05), higher mortality rates (40% and 46.2% vs. 0%, p < 0.05), significant lymphocytopenia (0.59 ± 0.31 × 109 /L and 0.56 ± 0.35 × 109 /L vs. 0.97 ± 0.33 × 109 /L, p < 0.05), and elevated neutrophil-to-lymphocyte ratio (NLR; 14.67 ± 6.10 and 14.64 ± 10.36 vs. 6.29 ± 3.72, p < 0.05). Compared with the H7N9 group, ground-glass opacity (GGO) on chest CT was common in the COVID-19 group (p = 0.028), while pleural effusion was rare (p = 0.001). CONCLUSIONS: The NLR can be used as a clinical parameter for the predication of risk stratification and outcome in COVID-19 and influenza A pneumonia. Manifestations of pleural effusion or GGO in chest CT may be helpful for the identification of different viral pneumonia.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , Influenza, Human/blood , Influenza, Human/diagnostic imaging , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/etiology , Chronic Disease , Critical Illness , Female , Humans , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza, Human/etiology , Influenza, Human/virology , Male , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Sex Factors
12.
Front Oncol ; 11: 753712, 2021.
Article in English | MEDLINE | ID: mdl-34778068

ABSTRACT

BACKGROUND: Among the growing number of patients with hematologic neoplasms hospitalized in the intensive care unit (ICU), the largest proportion of these patients are diagnosed with lymphoma. However, less attention has been paid in the past to identifying critically ill patients and assessing the prognosis of patients in ICU. Traditional critical care-related scores have shown limitations and inaccuracy in predicting mortality risk. METHODS: Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) were searched for in the Marketplace for Information in Intensive Care Medicine III (MIMIC-III) database. We searched mortality within 28 days as the primary endpoint. Logistics regression was used to screen risk factors. A calibration curve was used for internal validation, and the ROC curve and AUC were used to compare the new model with traditional scores. RESULTS: 405 patients with DLBCL are enrolled in the project. Multivariate analysis shows the patients with the level of lactate dehydrogenase (LDH) > 327 U/L had an increased risk of 28-day mortality in ICU than others (OR = 13.04, p<0.01). Notably, length of ICU stay, LDH, creatinine, white blood cell counts, and APS III score are independent prognostic factors for patients with DLBCL in the ICU. Then, all these independent prognostic factors are selected into our prediction model. The new model has good accuracy (C-index=0.863) and a calibration curve, which improves clinical status concerning established ratings such as IPI, NCCN-IPI score, SOFA, APS III, and LODS. The results of a multicenter external validation including 124 DLBCL patients also showed that the new model was more accurate than all other models. CONCLUSIONS: The elevated level of LDH indicates a poor prognosis of patients with DLBCL in the ICU. Our risk score with crossed validation based on the level of LDH shows a significant prognostic value and may be a valuable tool for assessing the critically ill as well.

13.
Oncol Rep ; 45(2): 764-775, 2021 02.
Article in English | MEDLINE | ID: mdl-33416178

ABSTRACT

Diffuse large B­cell lymphoma (DLBCL) is the most prevalent type of non­Hodgkin's lymphoma with a heterogeneous molecular pathogenesis and aggressive clinical manifestations. The aim of the present study was to investigate the role of miR­196a­3p and its target gene in the development and progression of DLBCL. RT­qPCR was used to detect the miR­196a­3p expression level in human DLBCL cell lines and DLBCL pathological tissues and compare them with the normal control. The clinical significance of the miR­196a­3p expression was also analyzed in DLBCL patients. Next, the effect of miR­196a­3p overexpression on the cell cycle, apoptosis, and proliferation of DLBCL cells was evaluated. To explore its underlying mechanism, the target gene of miR­196a­3p was predicted and validated using bioinformatics and molecular biological approaches. Finally, the expression of this target gene in clinical specimens and its correlation with clinicopathological characteristics were determined. The decreased expression of miR­196a­3p was validated in DLBCL, with further analysis proving that it was correlated with poor prognosis. It was shown that the overexpression of miR­196a­3p was associated with cell cycle arrest, enhanced apoptosis, and inhibited proliferation in DLBCL cells. Furthermore, ADP ribosylation factor 4 (ARF4) was verified as the downstream target gene of miR­196a­3p. Similar to miR­196a­3p restoration in vitro, endogenous ARF4­knockdown was proven to inhibit cell proliferation through cell cycle arrest and elevate apoptosis in DLBCL. The present results indicated that miR­196a­3p downregulation contributed to the tumorigenesis of DLBCL by targeting ARF4 expression, which may be used as a novel prognostic marker or potential molecular therapeutic target for DLBCL management in the future.


Subject(s)
ADP-Ribosylation Factors/genetics , Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/genetics , MicroRNAs/metabolism , Apoptosis/genetics , Biopsy , Bone Marrow/pathology , Carcinogenesis/genetics , Cell Cycle Checkpoints/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Female , Gene Knockdown Techniques , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged
14.
J Exp Clin Cancer Res ; 39(1): 237, 2020 Nov 09.
Article in English | MEDLINE | ID: mdl-33168041

ABSTRACT

BACKGROUND: In follicular lymphoma (FL), histologic transformation to high-grade FL and diffuse large B-cell lymphoma (DLBCL) is a critical adverse step in disease progression. Activation of the oncogene c-MYC and tumor microenvironment remodeling account for FL progression. A panel of microRNA (miRNA) was downregulated in transformed FL (tFL). METHODS: Differentially expressed miRNAs were systematically compared in 11 lymph nodes from patients at different stages of disease. Expression of miR-7e-5p was analyzed in 46 B-cell lymphomas, including 30 FL tissues and 16 DLBCL tissues. In FL cells, transcriptional regulation of the oncogene c-MYC on its target miR-7e-5p was revealed by Chromatin Immunoprecipitation (ChIP) assay. Exosome, carrying differentially expressed miR-7e-5p was isolated and visualized by transmission electron microscope and fluorescence tracing. The effect of miR-7e-5p on recipient macrophage was determined by target gene quantification, flow cytometry, and TUNEL method in a cocultured system with miR-7e-5p-mimics or inhibitors treatment. Expression of miR-7e-5p targets, macrophage proportions, and clinical parameters were included for correlation analysis. RESULTS: We determined that downregulation of miR-7e-5p, driven by c-MYC overexpression, was associated with poorer prognosis in FL patients. The decreased expression of miR-7e-5p in lymphoma cells led to a reduced exosomal transfer to surrounding macrophages. As a result, the target gene of miR-7e-5p, Fas ligand (FasL), was upregulated and activated the caspase signaling, which led to the apoptosis of M1 macrophages in tumor stroma. Finally, in transformed FL tissues, overexpression of FasL and activation of caspase proteins was detected in tumor stromal macrophages. Downregulation of miR-7e-5p was associated with poorer clinical outcomes. CONCLUSION: Downregulation of exosomal miR-7e-5p induces stromal M1 macrophage apoptosis, which leads to immunosurveillance and transformation of FL.


Subject(s)
Fas Ligand Protein/immunology , Lymphoma, Follicular/immunology , Macrophages/metabolism , MicroRNAs/immunology , Down-Regulation , Fas Ligand Protein/metabolism , Female , Humans , Lymphoma, Follicular/genetics , Lymphoma, Follicular/pathology , Macrophages/pathology , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Middle Aged , Neoplasm Grading , Stromal Cells/immunology , Stromal Cells/pathology , Transfection , Up-Regulation
16.
Thromb Res ; 192: 3-8, 2020 08.
Article in English | MEDLINE | ID: mdl-32407937

ABSTRACT

OBJECTIVE: To investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. METHOD: Confirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. RESULT: 75 patients were enrolled, with a mean age of 46.6 ±â€¯14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P < 0.05) than the mild/moderate, and the lymphocyte was lower. The ROC test showed that the hematological parameters had a larger AUC than that of inflammatory factors. There was a significant difference in lymphocyte and fibrinogen levels between the two groups on day 1 (P < 0.05). However, NLR of the severe group was higher than the mild/moderate on days 1, 4 and 14 (P < 0.01), and so was D-dimer on days 1, 7 and 14 (P < 0.05). CONCLUSION: The common COVID-19 abnormal hematological indexes on admission included hyperfibrinogenemia, lymphopenia, the elevation of D-dimer, and leukopenia, which were significantly different between the mild/moderate and severe COVID-19 groups. Furthermore, the dynamic change of NLR and D-dimer level can distinguish severe COVID-19 cases from the mild/moderate.


Subject(s)
Betacoronavirus/pathogenicity , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Fibrin Fibrinogen Degradation Products/analysis , Lymphocytes , Neutrophils , Pneumonia, Viral/diagnosis , Adult , Aged , Biomarkers/blood , COVID-19 , COVID-19 Testing , China , Coronavirus Infections/blood , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , Host-Pathogen Interactions , Humans , Lymphocyte Count , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Predictive Value of Tests , Prognosis , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
17.
Leukemia ; 34(3): 821-830, 2020 03.
Article in English | MEDLINE | ID: mdl-31624374

ABSTRACT

CD19-redirected CAR-T immunotherapy has emerged as a promising strategy for treatment of B cell lymphoma, however, many patients often relapsed due to antigen loss. Therefore, it is urgently needed to explore other suitable antigens targeted by CAR-T cells to cure B cell lymphoma. Igß is a component of the B cell receptor (BCR) complex, which is highly expressed on the surface of lymphoma cells. In this study, we engineered T cells to express anti-Igß CAR with CD28 costimulatory signaling moiety and observed that Igß-CAR T cells could efficiently recognize and eliminate Igß+ lymphoma cells both in vitro and in two different lymphoma xenograft models. The specificity of Igß-CAR T cells was further confirmed through wild type or mutated Igß gene transduction together with Igß-specific knockout in target cells. Of note, both the in vitro and in vivo effect of Igß CAR-T cells was comparable with that of CD19 CAR-T cells. Importantly, Igß CAR-T cells recognized and eradicated patient-derived lymphoma cells in the autologous setting. Lastly, the safety of anti-Igß CAR-T cells could be further enhanced by introduction of the inducible caspase-9 suicide gene system. Collectively, Igß-specific CAR-T cells may be a promising immunotherapeutic approach for B cell lymphoma.


Subject(s)
CD79 Antigens/immunology , Immunotherapy, Adoptive , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/therapy , T-Lymphocytes/immunology , Animals , CD28 Antigens/metabolism , Cell Line, Tumor , Coculture Techniques , Humans , K562 Cells , Lysosomal-Associated Membrane Protein 1/metabolism , Mice , Mice, Inbred NOD , Mice, SCID , Mutation , Neoplasm Transplantation , Receptors, Chimeric Antigen/immunology
18.
PLoS One ; 14(4): e0215656, 2019.
Article in English | MEDLINE | ID: mdl-31034481

ABSTRACT

Data about human trajectories has been widely used to study urban regions that are attractive to researchers and are considered to be hotspots. It is difficult, however, to quantify the function of urban regions based on the varieties of human behavior. In this research, we developed a clustering method to help discover the specific functions that exist within urban regions. This method applies the Gaussian Mixture Model (GMM) to classify regions' inflow and trip count characteristics. It regroups these urban regions using the Pearson Correlation Coefficient (PCC) clustering method based on those typical characteristics. Using a large amount of vehicle trajectory data (approximately 1,500,000 data points) in the Chinese city of Chengdu, we demonstrate that the method can discriminate between urban functional regions, by comparing the proportion of surface objects within each region. This research shows that vehicle trajectory data in different functional urban regions possesses different time-series curves, while similar types of functional regions can be identified by these curves. Compared with remote sensing images and other statistical methods which can provide only static results, our research can provide a timely and effective approach to determine an urban region's functions.


Subject(s)
Motor Vehicles/statistics & numerical data , Urban Population/statistics & numerical data , China , Cities , Cluster Analysis , Humans , Models, Statistical , Normal Distribution , Remote Sensing Technology , Travel/statistics & numerical data
19.
Cancer Sci ; 110(2): 805-816, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30536996

ABSTRACT

MicroRNAs, which regulate mRNAs, operate through a variety of signaling pathways to participate in the development of colorectal cancer (CRC). In this study, we found that microRNA (miR)-143-3p expression was significantly lower in both CRC and liver metastatic CRC tissues from liver compared with normal colonic tissues. Functional assays showed that miR-143-3p inhibited CRC cell invasion and migration in vitro. Using a bioinformatics approach, we identified miR-143-3p target mRNAs. Among the candidate targets, only the expression of integrin alpha 6 (ITGA6) and ArfGAP with the SH3 domain and ankyrin repeat and PH domain 3 (ASAP3) were significantly reduced by miR-143-3p mimics as examined by western blot, and the metastasis potential of CRC cells was attenuated by endogenous ITGA6 and ASAP3 knockdown, determined by migration and invasion assays. Both ITGA6 and ASAP3 were upregulated in CRC tissues compared to normal tissues. Analysis of the relationship between clinicopathological features and ITGA6/ASAP3 protein expression in 200 patients with CRC showed a significant difference in positive ITGA6 expression between the early stage (I + II) and the advanced stage (III + IV), and ASAP3 expression levels positively correlated with metastasis in the lymph nodes. These results indicate that miR-143-3p acts as an anti-oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC.


Subject(s)
Cell Movement/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , GTPase-Activating Proteins/genetics , Integrin alpha6/genetics , Lymphatic Metastasis/genetics , MicroRNAs/genetics , Aged , Cell Line, Tumor , Down-Regulation/genetics , Female , Gene Expression Regulation, Neoplastic/genetics , HCT116 Cells , Humans , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , RNA, Messenger/genetics , Signal Transduction/genetics , Up-Regulation/genetics
20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 29(6): 481-485, 2017 Jun.
Article in Chinese | MEDLINE | ID: mdl-28625233

ABSTRACT

OBJECTIVE: To investigate the association of red cell distribution width (RDW) with prognosis in patients with sepsis. METHODS: Patients with sepsis admitted to intensive care unit (ICU) of the First Hospital of Soochow University from January 2011 to December 2016 were enrolled. All clinical data were collected for participants, which mainly included basic data, main underlying disease, site of infection, acute physiology and chronic health evaluation II(APACHE II) score, blood routine test, biochemical test, blood gas analysis, coagulation index, procalcitonin (PCT), hospitalization days, and 28-day and 90-day mortality. Patients were divided into two groups according to whether the RDW levels were higher than the time of admission or not. Kaplan-Meier survival curve was performed to analyze 28-day and 90-day cumulative survival rates in two groups. Multivariate Cox regression analysis was done to find the independent risk factors of death in patients with sepsis. RESULTS: 196 septic patients were eligible to participate into this study. 150 patients (53.57%) had higher RDW levels than those at the time of admission. Compared to negative or static change of RDW group, positive change of RDW group had higher APACHE II score (20.42±6.29 vs. 16.17±6.37), more percentage of chronic kidney insufficiency (35.24% vs. 19.78%), bloodstream infection (32.38% vs. 15.38%), continuous renal replacement therapy (CRRT: 32.38% vs. 16.48%), higher level of C-reactive protein [CRP (mg/L): 14.71±3.52 vs. 11.15±7.94], and higher serum creatinine [SCr (µmol/L): 128.0 (74.0, 263.5) vs. 90.0 (57.0, 145.5)], PCT [µg/L: 3.45 (2.39, 6.64) vs. 2.35 (0.56, 3.54)], and lactic acid [Lac (mmol/L): 3.40±1.72 vs. 2.70±1.61]; and had lower levels of hematocrit (Hct: 0.357±0.128 vs. 0.437±0.143), hemoglobin [Hb (g/L): 103.60±22.63 vs. 115.67±28.49], platelets [PLT (×109/L): 133.37±87.29 vs. 191.43±87.65], albumin [Alb (g/L): 28.15±5.72 vs. 35.51±5.91], total cholesterol [TC (mmol/L): 2.43±1.12 vs. 3.05±1.55], estimated glomerular filtration rate [eGFR (mL×min-1×1.73 m-2): 82.02±63.90 vs. 125.46±83.47], and oxygenation index [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 229.69±60.61 vs. 264.21±74.78]; and longer time of hospitalization [days: 17.0 (12.0, 21.7) vs. 11.0 (7.0, 18.0)], higher 28-day and 90-day mortality (57.14% vs. 36.26%, 62.86% vs. 47.25%) with statistically significant differences (all P < 0.05). It was shown by Kaplan-Meier survival curve that the 28-day and 90-day cumulative survival rate in positive change of RDW group was significantly lower than that of negative or static change of RDW group (χ 12 = 8.462, χ 22 = 6.411, both P < 0.05). It was shown by multivariate Cox regression that high APACHE II score [odds ratio (OR) = 1.049, 95% confidence interval (95%CI) = 1.010-1.090, P = 0.013] and positive change of RDW (OR = 0.517, 95%CI = 0.280-0.953, P = 0.034) were the risk factors of death in patients with sepsis. CONCLUSIONS: The change of RDW values during hospitalization was related to the poor outcomes in patients with sepsis. The increase of RDW predicts the progress of sepsis and bad prognosis. Serial surveillance of RDW values could provide useful information for long-term prognosis in sepsis.


Subject(s)
Sepsis , APACHE , Calcitonin , Erythrocyte Indices , Hospitalization , Humans , Intensive Care Units , Prognosis , Retrospective Studies
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