Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and prog...Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival(PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-yearold patient who presented with progressive slurring of speech and features of raised intracranial pressure. Computed tomography(CT) scan revealed a large heterogeneously enhancing lesion in the left front-temporalperisylvian region with solid, cystic areas, suggestive of malignant glioma. Partial tumor-excision was followed by concurrent chemo-radiotherapy. Histopathologically, the tumor was astrocytoma grade-IV. Patient had an extended PFS of 12 mo, with an overall survival of 26 mo. Primary-GBM was confirmed using molecular markers and the immunophenotypic signature was defined by evaluating systemic expression of human telomerase reverse transcriptase, interleukin-6, neutrophil-lymphocyte ratio, tissue inhibitor of metalloproteinases-1, human chitinase-3-like-protein-1(YKL-40) and high mobility group-A1. Current findings suggest that this signature can identify worst outcomes, independent of clinical criteria.展开更多
BACKGROUND Multipotent mesenchymal stromal cells(MSCs)are widely used in the clinic due to their unique properties,namely,their ability to differentiate in all mesenchymal directions and their immunomodulatory activit...BACKGROUND Multipotent mesenchymal stromal cells(MSCs)are widely used in the clinic due to their unique properties,namely,their ability to differentiate in all mesenchymal directions and their immunomodulatory activity.Healthy donor MSCs were used to prevent the development of acute graft vs host disease(GVHD)after allogeneic bone marrow transplantation(allo-BMT).The administration of MSCs to patients was not always effective.The MSCs obtained from different donors have individual characteristics.The differences between MSC samples may affect their clinical efficacy.AIM To study the differences between effective and ineffective MSCs.METHODS MSCs derived from the bone marrow of a hematopoietic stem cells donor were injected intravenously into allo-BMT recipients for GVHD prophylaxis at the moment of blood cell reconstitution.Aliquots of 52 MSC samples that were administered to patients were examined,and the same cells were cultured in the presence of peripheral blood mononuclear cells(PBMCs)from a third-party donor or treated with the pro-inflammatory cytokines IL-1β,IFN and TNF.Flow cytometry revealed the immunophenotype of the nontreated MSCs,the MSCs cocultured with PBMCs for 4 d and the MSCs exposed to cytokines.The proportions of CD25-,CD146-,CD69-,HLA-DR-and PD-1-positive CD4+and CD8+cells and the distribution of various effector and memory cell subpopulations in the PBMCs cocultured with the MSCs were also determined.RESULTS Differences in the immunophenotypes of effective and ineffective MSCs were observed.In the effective samples,the mean fluorescence intensity(MFI)of HLAABC,HLA-DR,CD105,and CD146 was significantly higher.After MSCs were treated with IFN or cocultured with PBMCs,the HLA-ABC,HLA-DR,CD90 and CD54 MFI showed a stronger increase in the effective MSCs,which indicated an increase in the immunomodulatory activity of these cells.When PBMCs were cocultured with effective MSCs,the proportions of CD4+and CD8+central memory cells significantly decreased,and the proportion of CD8+CD146+lymphocytes increased more than in the subpopulations of lymphocytes cocultured with MSC samples that were ineffective in the prevention of GVHD;in addition,the proportion of CD8+effector memory lymphocytes decreased in the PBMCs cocultured with the effective MSC samples but increased in the PBMCs cocultured with the ineffective MSC samples.The proportion of CD4+CD146+lymphocytes increased only when cocultured with the inefficient samples.CONCLUSION For the first time,differences were observed between MSC samples that were effective for GVHD prophylaxis and those that were ineffective.Thus,it was shown that the immunomodulatory activity of MSCs depends on the individual characteristics of the MSC population.展开更多
To investigate the changes on the immunopbenotypes and the clinical effects of treatment of the late cancer patients with infusion of human peripheral blood lymphocytes stimulated by anti-CD28 and anti-CD80 monoclonal...To investigate the changes on the immunopbenotypes and the clinical effects of treatment of the late cancer patients with infusion of human peripheral blood lymphocytes stimulated by anti-CD28 and anti-CD80 monoclonal antibodies in combination with radiotherapy and chemotherapy, 42 patients with late cancers were collected for study, among which 22 patients were treated with infusion of stimulated lymphocytes in combination with radiotherapy and chemotherapy. The immunological treatment procedure was given twice per week, and one course of treatment consisted of 8 times of giving infusion of lymphocytes. Another 20 patients were selected for control group, in which only radiotherapy and chemotherapy were given without lymphocyte infusions. Flow cytometry was used to examine the immunophenotypes and the clinical symptoms were observed before and after treatments. It was found that the numbers of the CD3^ + , CD4^+ cells increased, while those of the CD8 ^+ cells decreased, with an increase of CD4/CD8 radios, but no significant difference existed in case of 22 patients treated with lymphocyte infusion as well as with radiotherapy and chemotherapy. Fifteen patients out of these 22 cases (68.18%), the immunophenotypes changed obviously with increased numbers of CD3^ + , CD4^ + cells in comparison with those before treatment, and the number of CD95^ + cells was increased after treatment. The PS value in this group of patients decreased after treatment. In comparison with 20 cases in the control group, the immunophenotypes showed no differences before and after treatment. While the PS value decreased obviously. Seven out of the 22 cases (31.83 % ) treated with lymphocyte infusions as well as with radiotherapy and chemotherapy illustrated no major changes in their i mmunophenotypes, compared with the situation before treatment, but the PS value also decreased. In case of treatment with lymphocyte infusions in combination with radiotherapy and chemotherapy, the alteration of phenotypes was reversely correlated with the changes of clinical grades. Although there were 7 cases showing no major alterations of the immunological phenotypes, but their correlation was still evident. In the control group, neither alteration of immunophenotypes nor changes in clinical grades was found. It is concluded that immunotherapy in combination with radiotherapy and chemotherapy can relieve the side effects induced by radiotherapy and chemotherapy and also enhance the therapeutic efforts.展开更多
Acrylamide(AA)is a harmful substance widely found in infant and child biscuits;however,the health hazards of AA,especially endogenous AA,in the biscuit matrix is poorly understood.This study aimed to determine the eff...Acrylamide(AA)is a harmful substance widely found in infant and child biscuits;however,the health hazards of AA,especially endogenous AA,in the biscuit matrix is poorly understood.This study aimed to determine the effects of endogenous(0.11 mg/(kg bw·day))and exogenous(1.31,5.23,and 10.13 mg/(kg bw·day))AA exposure from biscuit diet on the hematology,hormone levels,immune function,and liver and kidney damage in growing female rat pups.For the hematological indices,a quadratic reduction was observed in percentage of neutrophils(Neu%)and percentage of eosinophils(Eos%)in the leukograms and in mean corpuscular hemoglobin concentration and platelet in the erythrograms in all the AA-exposed groups.In terms of hormones,extremely remarkably elevations in estradiol(E_(2))and growth hormone(GH)levels were associated with exogenous AA,and a significant increase in GH levels was noted in the endogenous AA group.Regarding immune function,endogenous and exogenous AA showed a dose-dependent immunotoxic effect on lysozyme(LYSO),nitric oxide(NO),immunoglobulin(Ig)G,and IgM.In particular,the lactate dehydrogenase(LDH)activity was significantly high in the exogenous medium dose(Exo-M)and exogenous high dose(Exo-H)groups,and the percentage of CD3^(+)T cells in the blood and CD8^(+)expression levels in the spleen were significantly elevated in the Exo-H group.For liver and kidney function,exogenous AA had a dose-dependent effect on alanine aminotransferases(ALT),aspartate transferases(AST),alkaline phosphatase(ALP),urea nitrogen(UREA),and creatinine(CREA-S).In addition to the dose-dependent effect on the pathological changes in the liver and kidneys,the endogenous AA group presented with hepatocellular steatosis,kidney inflammatory infiltrates,and glomerular and tubular atrophy.Overall,our findings suggested the dose-dependent harmful effect of endogenous and exogenous AA.Special attention should be paid to the damage caused by exposure to endogenous AA.Stringent AA intake guidelines and measures are required to minimize AA levels in the food matrix.展开更多
Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of t...Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers,but also enables the detection of solid tumors.Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities,such as in fine-needle biopsy samples.This attribute not only addresses the challenge posed by small sample sizes,but also boosts the sensitivity of tumor cell detection.The significance of FCM in clinical and pathological applications continues to grow.To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process,experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus.This consensus was formulated based on current literature and clinical practices of all experts across clinical,laboratory,and pathological fields in China.It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples,including report content,interpretation,quality control,and key considerations.Additionally,it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests,particularly in cases with limited sample sizes.展开更多
Background Very few researchers have studied the changes in peripheral lymphocyte patterns in adult tuberculosis (TB) and even less researches have been conducted in pediatric TB.In this study,we obtained blood samp...Background Very few researchers have studied the changes in peripheral lymphocyte patterns in adult tuberculosis (TB) and even less researches have been conducted in pediatric TB.In this study,we obtained blood samples from 114 Chinese pediatric TB patients and 116 matched controls to study the association of phenotypic subsets of peripheral lymphocytes with different clinical phenotypes of TB.Methods The subjects were classified as the control group and the TB patients group which were further divided into a pulmonary TB group and an extra-pulmonary TB group (more serious than the former).The distribution of lymphocyte subpopulations,including T lymphocytes,CD4+ T lymphocytes,CD8+ T lymphocytes,B lymphocytes,and natural killer (NK) cells,were quantitatively analyzed by flow cytometry.Results Compared to the healthy controls,TB infection was associated with significantly higher B cell (P 〈0.0001),and lower T cell (P=0.029) and NK cell (P 〈0.0001) percentages.Compared to pulmonary TB patients,extra-pulmonary TB was associated with relatively higher B cell (P=0.073),and lower T cell percentages (P=-0.021),higher purified protein derivative (PPD) negative rate (P=-0.061),and poorer PPD response (P=-0.010).Most pulmonary TB cases were primary pulmonary TB (89.1%),and most extra-pulmonary TB cases had TB meningitis (72.1%).Conclusions This study demonstrates changes in the lymhocyte distribution in children suffering from different clinical phenotypes of TB; such as primary pulmonary TB,and TB meningitis.These patterns may have significance in understanding the pathogenesis and prognostic markers of the disease,and for developing immunomodulatory modalities of therapy.展开更多
Background Primary systemic light chain amyloidosis (AL) is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore wh...Background Primary systemic light chain amyloidosis (AL) is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry (FCM) could be used as an important indicator of AL diagnosis.Methods Fresh bone marrow samples were collected from 51 AL,21 multiple myeloma (MM),and 5 Waldenstr(o)m's macroglobulinemia (WM) patients.The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45,CD38,CD138,CD117,CD56,and CD19.Results In AL,light chain restriction could be identified in 31 cases (60.9%),in which the λ light chain restriction was found in 24 cases (77.4%).In MM,κ light chain restriction was found in 13 cases (61.9%),and λ light chain restriction in eight cases.CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM,but was positive to strongly positive in WM.In the bone marrow plasma cells of the 51 AL,78.4% were CD56+,68.6% were CD117+,and 88.2% were CD19-.While in the 21 MM cases,66.7% were CD56+,38.1% were CD117+,and 90.4% were CD19-.The plasmacytoid lymphocytes in the five WM patients were CD19+ and CD56-,CD117-.Conclusion Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.展开更多
BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I...BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.展开更多
We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin m...We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.展开更多
BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,ly...BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.展开更多
Introduction: Since it is impossible to establish a diagnosis in the presence of hyperlymphocytosis not secondary to lymphocytic hyperactivation, we considered a B-lymphoid hematopathy with a non-specific phenotypic p...Introduction: Since it is impossible to establish a diagnosis in the presence of hyperlymphocytosis not secondary to lymphocytic hyperactivation, we considered a B-lymphoid hematopathy with a non-specific phenotypic profile. We report one case of this. Observation: This is a forty-eight (48) year old patient with hyperlymphocytosis at 139,000 elements per cubic millimeter, heterogeneous splenomegaly at 25.6 cm in diameter on abdominal ultrasound without detectable deep or peripheral lymphadenopathy. Peripheral blood cytology shows lymphocyte cell proliferation suggestive of the circulating phase of chronic lymphoproliferative B syndrome. The expression profile of cell membrane markers did not allow for the definition of a specific phenotypic profile. Faced with this immunophenotyping result, we considered a B-lymphoid hemopathy with a non-specific phenotypic profile. After three courses, the MINICHOP treatment was used to achieve partial remission with wasting of more than 80% of the evaluable masses. Conclusion: Despite the contribution of immunophenotyping in the diagnosis of lymphoproliferative syndromes, it is possible to consider the diagnosis of a B-lymphoid hemopathy with a phenotypic non-specific profile of CD45+, monotypic kappa, CD19+, FMC7+, CD22+, CD5−, CD79b−, CD23−, CD43−, CD38−, CD200−.展开更多
Objective: To study the characteristics of immunophenotype in acute lymphoblastic leukemia (ALL) and its clinical significance. Methods: Immunophenotyping was performed on 81 ALL patients by three-color flow cytom...Objective: To study the characteristics of immunophenotype in acute lymphoblastic leukemia (ALL) and its clinical significance. Methods: Immunophenotyping was performed on 81 ALL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed on 45 cases out of 81 ALL patients. Results: (1) CD19 was the most commonly expressed of all B-lineage antigens detected with the positive rate being 100%. In T-ALL, the positive expression rate of CD5 and CD7 was the highest, being 90%. Both B-ALL and T-ALL overlapped in expression of lineage antigens. There was no significant difference in the complete remission rate (CR rate) between T-ALL and B-ALL. (2) The incidence of ALL with rayeloid antigens expression (My+ALL) was 39.5%. CD13 was most often seen among the myeloid markers. My+ALL always involved in B-lineage antigens and the CR rate in children and adults was 72.2% and 78.6% respectively. (3) The incidence of HAL was 19.8%. Coexpression of B-lineage and myeloid-assoeiated antigens was the commonest subtype in HAL. The expression of CD34 was commonly seen in HAL patients (81.3%). The CR rate was low in HAL, 50% for children and 40% for adults. (4) Compared to T-ALL, B-ALL, My+ALL, and HAL had a higher positive rate of CD34 expression with the difference being significant (P〈0.025). Conclusion: Immunophenotyping had remarkable predominance in diagnosing special category of ALL (such as HAL and My+ALL); CD19 and CD5 were highly sensitive in diagnosing B-ALL and T-ALL, but less special, and overlapping was found in expression. No significant association was found between the expression of CD34 or myeloid antigens and CR rate, while low CR rate was found in HAL patients, especially for those coexpressing CD34 antigen.展开更多
BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is a rare and rapidly progressive intestinal T-cell non-Hodgkin lymphoma associated with a very poor prognosis and a median survival of 7 mo.Adva...BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is a rare and rapidly progressive intestinal T-cell non-Hodgkin lymphoma associated with a very poor prognosis and a median survival of 7 mo.Advances in the identification of MEITL over the last two decades have led to its recognition as a separate entity.MEITL patients,predominantly male,typically present with vague and nonspecific symptoms and diagnosis is predominantly confirmed at laparotomy.Currently,there are no standardized treatment protocols,and the optimal therapy remains unclear.CASE SUMMARY We report a case of MEITL that was initially considered to be gastrointestinal stromal tumor(GIST)and Imatinib was administered for one cycle.The 62-yearold man presented with abdominal pain,abdominal distension,and weight loss of 20 pounds.Within 2 wk,the size of the mass considerably increased on computed tomography scans.The patient underwent surgery followed by chemotherapy with CHOP(cyclophosphamide,doxorubicin,vincristine,and prednisone)and stem-cell transplant.A correct diagnosis of MEITL was established based on postoperative pathology.Immunophenotypically,the neoplastic cells fulfilled the diagnostic criteria for MEITL as they were CD3+,CD4+,CD8+,CD56+,and TIA-1+.CONCLUSION Given that MEITL has no predisposing factor and presents with vague symptoms with rapid progression,the concomitant presence of abdominal symptoms and B symptoms(weight loss,fever,and night sweats)with hypoalbuminemia,anemia,low lymphocytic count and endoscopic findings of diffuse infiltrating type lesions should alert physicians to this rare disease,especially when it comes to Asian patients.Immediate laparotomy should then be carried out followed by chemotherapy and stem-cell transplant.展开更多
AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation ra...AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay. RESULTS: The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P【0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P【0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might serve as an alternative adoptive therapeutic strategy for HCC patients.展开更多
Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor pro...Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.展开更多
AIM: To explore the feasibility of placenta tissue as a reliable and efficient source for generating mesenchymal stem cells (MSC). METHODS: MSC were generated from human placenta tissue by enzymatic digestion and mech...AIM: To explore the feasibility of placenta tissue as a reliable and efficient source for generating mesenchymal stem cells (MSC). METHODS: MSC were generated from human placenta tissue by enzymatic digestion and mechanical dissociation. The placenta MSC (PLC-MSC) were characterized for expression of cell surface markers, embryonic stem cell (ECS) gene expression and their differentiation ability into adipocytes and osteocytes. The immunosuppressive properties of PLC-MSC on resting and phytohemagglutinin (PHA) stimulated allogenic T cells were assessed by means of cell proliferation via incorporation of tritium thymidine (3H-TdR). RESULTS: The generated PLC-MSC appeared as spindle-shaped cells, expressed common MSC surface markers and ESC transcriptional factors. They also differen-tiated into adipogenic and osteogenic lineages when induced. However, continuous cultivation up to passage 15 caused changes in morphological appearance and cellular senescence, although the stem cell nature of their protein expression was unchanged. In terms of their immunosuppressive properties, PLC-MSC were unable to stimulate resting T cell proliferation; they inhibited the PHA stimulated T cells in a dose dependent manner through cell to cell contact. In our study, MSC generated from human placenta exhibited similar mesenchymal cell surface markers; MSC-like gene expression pattern and MSC-like differentiation potential were comparable to other sources of MSC. CONCLUSION: We suggest that placenta tissues can serve as an alternative source of MSC for future experimental and clinical studies.展开更多
The immunophenotyping expression levels of lymphocyte in the peripheral blood from 21 patients with active systemic lupus erythematosus were analyzed by using the immunofluorescence labeling flow cytometry technique...The immunophenotyping expression levels of lymphocyte in the peripheral blood from 21 patients with active systemic lupus erythematosus were analyzed by using the immunofluorescence labeling flow cytometry technique to investigate the immunophenotyping expression of lymphocytes T and B in the peripheral blood of active SLE patients and its clinical value. It was showed that, compared with normal controls, the expression of CD + 3, CD + 4 and the ratio of CD + 4/CD + 8 in the peripheral blood of these patients were decreased , while the expression of CD + 8, CD + 20 was significantly increased . It was suggested that both T and B cells in patients with active SLE involved in immunoregulation, were activated. The abnormal expression of lymphocyte immunophenotyping could influence the immune reaction in SLE patients, which might be one of the important pathogenesis factors in SLE.展开更多
The role of endoscopic ultrasound(EUS) in evaluating pancreatic pathology has been well documented from the beginning of its clinical use. High spatial resolution and the close proximity to the evaluated organs within...The role of endoscopic ultrasound(EUS) in evaluating pancreatic pathology has been well documented from the beginning of its clinical use. High spatial resolution and the close proximity to the evaluated organs within the mediastinum and abdominal cavity allow detection of small focal lesions and precise tissue acquisition from suspected lesions within the reach of this method. Fine needle aspiration(FNA) is considered of additional value to EUS and is performed to obtain tissue diagnosis. Tissue acquisition from suspected lesions for cytological or histological analysis allows, not only the differentiation between malignant and non-malignant lesions, but, in most cases, also the accurate distinction between the various types of malignant lesions. It is well documented that the best results are achieved only if an adequate sample is obtained for further analysis, if the material is processed in an appropriate way, and if adequate ancillary methods are performed. This is a multi-step process and could be quite a challenge in some cases. In this article, we discuss the technical aspects of tissue acquisition by EUS-guided-FNA(EUS-FNA), as well as the role of an on-site cytopathologist, various means of specimen processing, and the selection of the appropriate ancillary method for providing an accurate tissue diagnosis and maximizing the yield of this method. The main goal of this review is to alert endosonographers, not only to the different possibilities of tissue acquisition, namely EUS-FNA, but also to bring to their attention the importance of proper sample processing in the evaluation of various lesions in the gastrointestinal tract and other accessible organs. All aspects of tissue acquisition(needles, suction, use of stylet, complications, etc.) have been well discussed lately. Adequate tissue samples enable comprehensive diagnoses, which answer the main clinical questions, thus enabling targeted therapy.展开更多
Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hype...Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.展开更多
Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL...Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.展开更多
基金Supported by M.P.Biotech Council,M.P.for financial assistance and BMHRC for infrastructural facilities,No.249
文摘Glioblastoma-multiforme(GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival(PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-yearold patient who presented with progressive slurring of speech and features of raised intracranial pressure. Computed tomography(CT) scan revealed a large heterogeneously enhancing lesion in the left front-temporalperisylvian region with solid, cystic areas, suggestive of malignant glioma. Partial tumor-excision was followed by concurrent chemo-radiotherapy. Histopathologically, the tumor was astrocytoma grade-IV. Patient had an extended PFS of 12 mo, with an overall survival of 26 mo. Primary-GBM was confirmed using molecular markers and the immunophenotypic signature was defined by evaluating systemic expression of human telomerase reverse transcriptase, interleukin-6, neutrophil-lymphocyte ratio, tissue inhibitor of metalloproteinases-1, human chitinase-3-like-protein-1(YKL-40) and high mobility group-A1. Current findings suggest that this signature can identify worst outcomes, independent of clinical criteria.
文摘BACKGROUND Multipotent mesenchymal stromal cells(MSCs)are widely used in the clinic due to their unique properties,namely,their ability to differentiate in all mesenchymal directions and their immunomodulatory activity.Healthy donor MSCs were used to prevent the development of acute graft vs host disease(GVHD)after allogeneic bone marrow transplantation(allo-BMT).The administration of MSCs to patients was not always effective.The MSCs obtained from different donors have individual characteristics.The differences between MSC samples may affect their clinical efficacy.AIM To study the differences between effective and ineffective MSCs.METHODS MSCs derived from the bone marrow of a hematopoietic stem cells donor were injected intravenously into allo-BMT recipients for GVHD prophylaxis at the moment of blood cell reconstitution.Aliquots of 52 MSC samples that were administered to patients were examined,and the same cells were cultured in the presence of peripheral blood mononuclear cells(PBMCs)from a third-party donor or treated with the pro-inflammatory cytokines IL-1β,IFN and TNF.Flow cytometry revealed the immunophenotype of the nontreated MSCs,the MSCs cocultured with PBMCs for 4 d and the MSCs exposed to cytokines.The proportions of CD25-,CD146-,CD69-,HLA-DR-and PD-1-positive CD4+and CD8+cells and the distribution of various effector and memory cell subpopulations in the PBMCs cocultured with the MSCs were also determined.RESULTS Differences in the immunophenotypes of effective and ineffective MSCs were observed.In the effective samples,the mean fluorescence intensity(MFI)of HLAABC,HLA-DR,CD105,and CD146 was significantly higher.After MSCs were treated with IFN or cocultured with PBMCs,the HLA-ABC,HLA-DR,CD90 and CD54 MFI showed a stronger increase in the effective MSCs,which indicated an increase in the immunomodulatory activity of these cells.When PBMCs were cocultured with effective MSCs,the proportions of CD4+and CD8+central memory cells significantly decreased,and the proportion of CD8+CD146+lymphocytes increased more than in the subpopulations of lymphocytes cocultured with MSC samples that were ineffective in the prevention of GVHD;in addition,the proportion of CD8+effector memory lymphocytes decreased in the PBMCs cocultured with the effective MSC samples but increased in the PBMCs cocultured with the ineffective MSC samples.The proportion of CD4+CD146+lymphocytes increased only when cocultured with the inefficient samples.CONCLUSION For the first time,differences were observed between MSC samples that were effective for GVHD prophylaxis and those that were ineffective.Thus,it was shown that the immunomodulatory activity of MSCs depends on the individual characteristics of the MSC population.
文摘To investigate the changes on the immunopbenotypes and the clinical effects of treatment of the late cancer patients with infusion of human peripheral blood lymphocytes stimulated by anti-CD28 and anti-CD80 monoclonal antibodies in combination with radiotherapy and chemotherapy, 42 patients with late cancers were collected for study, among which 22 patients were treated with infusion of stimulated lymphocytes in combination with radiotherapy and chemotherapy. The immunological treatment procedure was given twice per week, and one course of treatment consisted of 8 times of giving infusion of lymphocytes. Another 20 patients were selected for control group, in which only radiotherapy and chemotherapy were given without lymphocyte infusions. Flow cytometry was used to examine the immunophenotypes and the clinical symptoms were observed before and after treatments. It was found that the numbers of the CD3^ + , CD4^+ cells increased, while those of the CD8 ^+ cells decreased, with an increase of CD4/CD8 radios, but no significant difference existed in case of 22 patients treated with lymphocyte infusion as well as with radiotherapy and chemotherapy. Fifteen patients out of these 22 cases (68.18%), the immunophenotypes changed obviously with increased numbers of CD3^ + , CD4^ + cells in comparison with those before treatment, and the number of CD95^ + cells was increased after treatment. The PS value in this group of patients decreased after treatment. In comparison with 20 cases in the control group, the immunophenotypes showed no differences before and after treatment. While the PS value decreased obviously. Seven out of the 22 cases (31.83 % ) treated with lymphocyte infusions as well as with radiotherapy and chemotherapy illustrated no major changes in their i mmunophenotypes, compared with the situation before treatment, but the PS value also decreased. In case of treatment with lymphocyte infusions in combination with radiotherapy and chemotherapy, the alteration of phenotypes was reversely correlated with the changes of clinical grades. Although there were 7 cases showing no major alterations of the immunological phenotypes, but their correlation was still evident. In the control group, neither alteration of immunophenotypes nor changes in clinical grades was found. It is concluded that immunotherapy in combination with radiotherapy and chemotherapy can relieve the side effects induced by radiotherapy and chemotherapy and also enhance the therapeutic efforts.
文摘Acrylamide(AA)is a harmful substance widely found in infant and child biscuits;however,the health hazards of AA,especially endogenous AA,in the biscuit matrix is poorly understood.This study aimed to determine the effects of endogenous(0.11 mg/(kg bw·day))and exogenous(1.31,5.23,and 10.13 mg/(kg bw·day))AA exposure from biscuit diet on the hematology,hormone levels,immune function,and liver and kidney damage in growing female rat pups.For the hematological indices,a quadratic reduction was observed in percentage of neutrophils(Neu%)and percentage of eosinophils(Eos%)in the leukograms and in mean corpuscular hemoglobin concentration and platelet in the erythrograms in all the AA-exposed groups.In terms of hormones,extremely remarkably elevations in estradiol(E_(2))and growth hormone(GH)levels were associated with exogenous AA,and a significant increase in GH levels was noted in the endogenous AA group.Regarding immune function,endogenous and exogenous AA showed a dose-dependent immunotoxic effect on lysozyme(LYSO),nitric oxide(NO),immunoglobulin(Ig)G,and IgM.In particular,the lactate dehydrogenase(LDH)activity was significantly high in the exogenous medium dose(Exo-M)and exogenous high dose(Exo-H)groups,and the percentage of CD3^(+)T cells in the blood and CD8^(+)expression levels in the spleen were significantly elevated in the Exo-H group.For liver and kidney function,exogenous AA had a dose-dependent effect on alanine aminotransferases(ALT),aspartate transferases(AST),alkaline phosphatase(ALP),urea nitrogen(UREA),and creatinine(CREA-S).In addition to the dose-dependent effect on the pathological changes in the liver and kidneys,the endogenous AA group presented with hepatocellular steatosis,kidney inflammatory infiltrates,and glomerular and tubular atrophy.Overall,our findings suggested the dose-dependent harmful effect of endogenous and exogenous AA.Special attention should be paid to the damage caused by exposure to endogenous AA.Stringent AA intake guidelines and measures are required to minimize AA levels in the food matrix.
基金supported by grants from the National Natural Science Foundation of China(grant numbers:82370195,82270203,81770211)the Fundamental Research Funds for the Central Univer-sities(grant number:2022CDJYGRH-001)Chongqing Technology Innovation and Application Development Special Key Project(grant number:CSTB2024TIAD-KPX0031).
文摘Flow cytometry(FCM),characterized by its simplicity,rapid processing,multiparameter analysis,and high sen-sitivity,is widely used in the diagnosis,treatment,and prognosis of hematological malignancies.FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers,but also enables the detection of solid tumors.Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities,such as in fine-needle biopsy samples.This attribute not only addresses the challenge posed by small sample sizes,but also boosts the sensitivity of tumor cell detection.The significance of FCM in clinical and pathological applications continues to grow.To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process,experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus.This consensus was formulated based on current literature and clinical practices of all experts across clinical,laboratory,and pathological fields in China.It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples,including report content,interpretation,quality control,and key considerations.Additionally,it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests,particularly in cases with limited sample sizes.
文摘Background Very few researchers have studied the changes in peripheral lymphocyte patterns in adult tuberculosis (TB) and even less researches have been conducted in pediatric TB.In this study,we obtained blood samples from 114 Chinese pediatric TB patients and 116 matched controls to study the association of phenotypic subsets of peripheral lymphocytes with different clinical phenotypes of TB.Methods The subjects were classified as the control group and the TB patients group which were further divided into a pulmonary TB group and an extra-pulmonary TB group (more serious than the former).The distribution of lymphocyte subpopulations,including T lymphocytes,CD4+ T lymphocytes,CD8+ T lymphocytes,B lymphocytes,and natural killer (NK) cells,were quantitatively analyzed by flow cytometry.Results Compared to the healthy controls,TB infection was associated with significantly higher B cell (P 〈0.0001),and lower T cell (P=0.029) and NK cell (P 〈0.0001) percentages.Compared to pulmonary TB patients,extra-pulmonary TB was associated with relatively higher B cell (P=0.073),and lower T cell percentages (P=-0.021),higher purified protein derivative (PPD) negative rate (P=-0.061),and poorer PPD response (P=-0.010).Most pulmonary TB cases were primary pulmonary TB (89.1%),and most extra-pulmonary TB cases had TB meningitis (72.1%).Conclusions This study demonstrates changes in the lymhocyte distribution in children suffering from different clinical phenotypes of TB; such as primary pulmonary TB,and TB meningitis.These patterns may have significance in understanding the pathogenesis and prognostic markers of the disease,and for developing immunomodulatory modalities of therapy.
基金This work was funded by the National Natural Science Foundation of China (No.81370612) and the Youth Fund Project of the National Natural Science Foundation of China (No.81102211).
文摘Background Primary systemic light chain amyloidosis (AL) is a rare plasma cell disease,our purpose was to analyze the immunophenotypic characteristics of the plasma cells in bone marrow in AL patients,and explore whether the detection of abnormal plasma cell clones in bone marrow by flow cytometry (FCM) could be used as an important indicator of AL diagnosis.Methods Fresh bone marrow samples were collected from 51 AL,21 multiple myeloma (MM),and 5 Waldenstr(o)m's macroglobulinemia (WM) patients.The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45,CD38,CD138,CD117,CD56,and CD19.Results In AL,light chain restriction could be identified in 31 cases (60.9%),in which the λ light chain restriction was found in 24 cases (77.4%).In MM,κ light chain restriction was found in 13 cases (61.9%),and λ light chain restriction in eight cases.CD45 on abnormal plasma cells was negative to weakly positive in both AL and MM,but was positive to strongly positive in WM.In the bone marrow plasma cells of the 51 AL,78.4% were CD56+,68.6% were CD117+,and 88.2% were CD19-.While in the 21 MM cases,66.7% were CD56+,38.1% were CD117+,and 90.4% were CD19-.The plasmacytoid lymphocytes in the five WM patients were CD19+ and CD56-,CD117-.Conclusion Detection of abnormal plasma cell clones in bone marrow by FCM is valuable for the diagnosis of AL.
文摘BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
基金Supported by The Chongqing Health Commission and Science and Technology Bureau,No.2023MSXM060.
文摘We specifically discuss the mechanisms of the pathogenesis,diagnosis,and management of blastic plasmacytoid dendritic cell neoplasm(BPDCN),a rare but aggressive haematologic malignancy characterized by frequent skin manifestations and systemic dissemination.The article enriches our understanding of BPDCN through detailed case reports showing the clinical,immunophenotypic,and histopathological features that are critical for diagnosing this disease.These cases highlight the essential role of pathologists in employing advanced immunophenotyping techniques to accurately identify the disease early in its course and guide treatment decisions.Furthermore,we explore the implications of these findings for management strategies,emphasizing the use of targeted therapies such as tagraxofusp and the potential of allogeneic haematopoietic stem cell transplantation in achieving remission.The editorial underscores the importance of interdisciplinary approaches in managing BPDCN,pointing towards a future where precision medicine could significantly improve patient outcomes.
文摘BACKGROUND Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells.BPDCN often involves the skin,lymph nodes,and bone marrow,with rapid clinical progression and a poor prognosis.The BPDCN diagnosis is mainly based on the immunophenotype.CASE SUMMARY In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.CONCLUSION In this paper,we retrospectively analyzed 2 cases of BPDCN.Both patients were elderly males.The lesions manifested as skin masses.Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues.Immunohistochemistry staining showed that cluster of differentiation CD4,CD56,CD43,and CD123 were positive.
文摘Introduction: Since it is impossible to establish a diagnosis in the presence of hyperlymphocytosis not secondary to lymphocytic hyperactivation, we considered a B-lymphoid hematopathy with a non-specific phenotypic profile. We report one case of this. Observation: This is a forty-eight (48) year old patient with hyperlymphocytosis at 139,000 elements per cubic millimeter, heterogeneous splenomegaly at 25.6 cm in diameter on abdominal ultrasound without detectable deep or peripheral lymphadenopathy. Peripheral blood cytology shows lymphocyte cell proliferation suggestive of the circulating phase of chronic lymphoproliferative B syndrome. The expression profile of cell membrane markers did not allow for the definition of a specific phenotypic profile. Faced with this immunophenotyping result, we considered a B-lymphoid hemopathy with a non-specific phenotypic profile. After three courses, the MINICHOP treatment was used to achieve partial remission with wasting of more than 80% of the evaluable masses. Conclusion: Despite the contribution of immunophenotyping in the diagnosis of lymphoproliferative syndromes, it is possible to consider the diagnosis of a B-lymphoid hemopathy with a phenotypic non-specific profile of CD45+, monotypic kappa, CD19+, FMC7+, CD22+, CD5−, CD79b−, CD23−, CD43−, CD38−, CD200−.
文摘Objective: To study the characteristics of immunophenotype in acute lymphoblastic leukemia (ALL) and its clinical significance. Methods: Immunophenotyping was performed on 81 ALL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed on 45 cases out of 81 ALL patients. Results: (1) CD19 was the most commonly expressed of all B-lineage antigens detected with the positive rate being 100%. In T-ALL, the positive expression rate of CD5 and CD7 was the highest, being 90%. Both B-ALL and T-ALL overlapped in expression of lineage antigens. There was no significant difference in the complete remission rate (CR rate) between T-ALL and B-ALL. (2) The incidence of ALL with rayeloid antigens expression (My+ALL) was 39.5%. CD13 was most often seen among the myeloid markers. My+ALL always involved in B-lineage antigens and the CR rate in children and adults was 72.2% and 78.6% respectively. (3) The incidence of HAL was 19.8%. Coexpression of B-lineage and myeloid-assoeiated antigens was the commonest subtype in HAL. The expression of CD34 was commonly seen in HAL patients (81.3%). The CR rate was low in HAL, 50% for children and 40% for adults. (4) Compared to T-ALL, B-ALL, My+ALL, and HAL had a higher positive rate of CD34 expression with the difference being significant (P〈0.025). Conclusion: Immunophenotyping had remarkable predominance in diagnosing special category of ALL (such as HAL and My+ALL); CD19 and CD5 were highly sensitive in diagnosing B-ALL and T-ALL, but less special, and overlapping was found in expression. No significant association was found between the expression of CD34 or myeloid antigens and CR rate, while low CR rate was found in HAL patients, especially for those coexpressing CD34 antigen.
文摘BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is a rare and rapidly progressive intestinal T-cell non-Hodgkin lymphoma associated with a very poor prognosis and a median survival of 7 mo.Advances in the identification of MEITL over the last two decades have led to its recognition as a separate entity.MEITL patients,predominantly male,typically present with vague and nonspecific symptoms and diagnosis is predominantly confirmed at laparotomy.Currently,there are no standardized treatment protocols,and the optimal therapy remains unclear.CASE SUMMARY We report a case of MEITL that was initially considered to be gastrointestinal stromal tumor(GIST)and Imatinib was administered for one cycle.The 62-yearold man presented with abdominal pain,abdominal distension,and weight loss of 20 pounds.Within 2 wk,the size of the mass considerably increased on computed tomography scans.The patient underwent surgery followed by chemotherapy with CHOP(cyclophosphamide,doxorubicin,vincristine,and prednisone)and stem-cell transplant.A correct diagnosis of MEITL was established based on postoperative pathology.Immunophenotypically,the neoplastic cells fulfilled the diagnostic criteria for MEITL as they were CD3+,CD4+,CD8+,CD56+,and TIA-1+.CONCLUSION Given that MEITL has no predisposing factor and presents with vague symptoms with rapid progression,the concomitant presence of abdominal symptoms and B symptoms(weight loss,fever,and night sweats)with hypoalbuminemia,anemia,low lymphocytic count and endoscopic findings of diffuse infiltrating type lesions should alert physicians to this rare disease,especially when it comes to Asian patients.Immediate laparotomy should then be carried out followed by chemotherapy and stem-cell transplant.
基金Science and Technology Development Foundation of Beijing Institute of Infectious Diseases,No.01 Z094
文摘AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay. RESULTS: The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P【0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P【0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might serve as an alternative adoptive therapeutic strategy for HCC patients.
基金the National NaOiral Science Foundation of China(No.81460030,81770221).
文摘Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological malignancy characterized by recurrent skin nodules,an aggressive clinical course with rapid involvement of hematological organs,and a poor prognosis with poor overall survival.BPDCN is derived from plasmacytoid dendritic cells(pDCs)and its pathogenesis is unclear.The tumor cells show aberrant expression of CD4,CD56,interleukin-3 receptor alpha chain(CD 123),blood dendritic cell antigen 2(BDCA 2/CD303),blood dendritic cell antigen 4(BDCA4)and transcription factor(E protein)E2-2(TCF4).The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma.Relapse with drug resistance generally occurs quickly.Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy.In this review,we summarize the differentiation of BPDCN from its cell origin,its connection with normal pDCs,clinical characteristics,genetic mutations and advances in treatment of BPDCN.This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
基金Supported by Research University Grant Scheme, Universiti Putra Malaysia, No. 04-01-09-0781RUScience Fund, Ministry of Science, Technology and Innovation, Malaysia, No. 02-01-04-SF1022
文摘AIM: To explore the feasibility of placenta tissue as a reliable and efficient source for generating mesenchymal stem cells (MSC). METHODS: MSC were generated from human placenta tissue by enzymatic digestion and mechanical dissociation. The placenta MSC (PLC-MSC) were characterized for expression of cell surface markers, embryonic stem cell (ECS) gene expression and their differentiation ability into adipocytes and osteocytes. The immunosuppressive properties of PLC-MSC on resting and phytohemagglutinin (PHA) stimulated allogenic T cells were assessed by means of cell proliferation via incorporation of tritium thymidine (3H-TdR). RESULTS: The generated PLC-MSC appeared as spindle-shaped cells, expressed common MSC surface markers and ESC transcriptional factors. They also differen-tiated into adipogenic and osteogenic lineages when induced. However, continuous cultivation up to passage 15 caused changes in morphological appearance and cellular senescence, although the stem cell nature of their protein expression was unchanged. In terms of their immunosuppressive properties, PLC-MSC were unable to stimulate resting T cell proliferation; they inhibited the PHA stimulated T cells in a dose dependent manner through cell to cell contact. In our study, MSC generated from human placenta exhibited similar mesenchymal cell surface markers; MSC-like gene expression pattern and MSC-like differentiation potential were comparable to other sources of MSC. CONCLUSION: We suggest that placenta tissues can serve as an alternative source of MSC for future experimental and clinical studies.
文摘The immunophenotyping expression levels of lymphocyte in the peripheral blood from 21 patients with active systemic lupus erythematosus were analyzed by using the immunofluorescence labeling flow cytometry technique to investigate the immunophenotyping expression of lymphocytes T and B in the peripheral blood of active SLE patients and its clinical value. It was showed that, compared with normal controls, the expression of CD + 3, CD + 4 and the ratio of CD + 4/CD + 8 in the peripheral blood of these patients were decreased , while the expression of CD + 8, CD + 20 was significantly increased . It was suggested that both T and B cells in patients with active SLE involved in immunoregulation, were activated. The abnormal expression of lymphocyte immunophenotyping could influence the immune reaction in SLE patients, which might be one of the important pathogenesis factors in SLE.
文摘The role of endoscopic ultrasound(EUS) in evaluating pancreatic pathology has been well documented from the beginning of its clinical use. High spatial resolution and the close proximity to the evaluated organs within the mediastinum and abdominal cavity allow detection of small focal lesions and precise tissue acquisition from suspected lesions within the reach of this method. Fine needle aspiration(FNA) is considered of additional value to EUS and is performed to obtain tissue diagnosis. Tissue acquisition from suspected lesions for cytological or histological analysis allows, not only the differentiation between malignant and non-malignant lesions, but, in most cases, also the accurate distinction between the various types of malignant lesions. It is well documented that the best results are achieved only if an adequate sample is obtained for further analysis, if the material is processed in an appropriate way, and if adequate ancillary methods are performed. This is a multi-step process and could be quite a challenge in some cases. In this article, we discuss the technical aspects of tissue acquisition by EUS-guided-FNA(EUS-FNA), as well as the role of an on-site cytopathologist, various means of specimen processing, and the selection of the appropriate ancillary method for providing an accurate tissue diagnosis and maximizing the yield of this method. The main goal of this review is to alert endosonographers, not only to the different possibilities of tissue acquisition, namely EUS-FNA, but also to bring to their attention the importance of proper sample processing in the evaluation of various lesions in the gastrointestinal tract and other accessible organs. All aspects of tissue acquisition(needles, suction, use of stylet, complications, etc.) have been well discussed lately. Adequate tissue samples enable comprehensive diagnoses, which answer the main clinical questions, thus enabling targeted therapy.
基金Supported by CAPES, INCT-MM (FAPEMIG: CBB-APQ- 00075-09/CNPq 573646/2008-2)
文摘Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.
基金supported by grants from the National Basic Research Program of China (No.2007CB947802)the Natural Science Foundation of China to H.X. (No.30771228) and to X.M. (No.30771227)
文摘Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.