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OBJECTIVE@#To investigate the expressions of CD33 and CD13 in newly diagnosed multiple myeloma (MM) patients and its relationship with prognosis.@*METHODS@#It was retrospectively observed that the expression of CD33 and CD13 in 121 MM patients who were newly diagnosed from January 2014 to January 2020, and the relationship between the expressions of CD33 and CD13 and patients prognosis was analyzed.@*RESULTS@#Among the 121 newly diagnosed MM patients, there were 30 patients (24.8%) in the CD33+ group and 12 patients (9.9%) in the CD13+ group. Kaplan-Meier analysis showed that, compared with the CD33- group, the progression-free survival (PFS) time and overall survival (OS) time were significantly shortened in MM patients in CD33+ group (PFS 17.5 vs 23 months, P=0.000; OS 18.5 vs 25 months, P=0.000); and the PFS time and OS time of MM patients in the CD13+ group were also significantly shortened than those in CD13- group (PFS 21 vs 22 months, P=0.012; OS 25 vs 26 months, P=0.006). Cox regression analysis showed that CD33 and CD13 were independent adverse prognostic factors in MM patients (CD33: P=0.000;CD13: P=0.003).@*CONCLUSION@#CD33 and CD13 are prognostic risk factors in patients with MM.
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Humans , CD13 Antigens , Cell Count , Kaplan-Meier Estimate , Multiple Myeloma , Prognosis , Retrospective Studies , Sialic Acid Binding Ig-like Lectin 3ABSTRACT
Tumor neovascularization plays an important role in the occurrence, development and metastasis of cancer. Non-invasive quantification and detection of tumor neovascularization is crucial for early diagnosis and prognosis assessment of cancer. Targeted molecular imaging has arisen in vascular targeting imaging and precise treatment based on the molecular characteristics of neovascularization. Aminopeptidase N (APN, or CD13) is a multifunctional membrane-bound exopeptidase that is overexpressed in neovascular endothelial cells and some tumor cells but rarely expressed in normal blood vessels, which makes it a potential target for tumor neovascularization imaging and anti-angiogenic therapy. This review summarizes the application progress and the future development trend of target molecular imaging and precise treatment based on CD13.
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OBJECTIVE: To investigate the inhibitory effects of bispecific antibody-drug conjugate Fv-LDM-NGR targeting EGFR and CD13 on human tumor cells and endothelial cells,and possible mechanisms. METHODS: Human breast cancer cells MCF-7, human lung adenocarcinoma cells A549 and human microvascular endothelial cells HMEC-1, were studied. MTT assay was applied to measure proliferative activity of tumor cells. The influence of Fv-LDM-NGR on tube formation of HMEC-1 was observed. Transwell assay was applied to measure migration and invasion capacity in tumor cells. Western blot was applied for analyzing intracellular signaling transduction pathways. Flow cytometry, Hochest stain and Annexin -FITC/PI were used to detect cell cycle and apoptosis. RESULTS: Fv-LDM-NGR could inhibit the proliferation of tumor cells and microvascular endothelial cells with IC50 values of 10-14-10-12mol•L-1. Fv-LDM-NGR prevented tube formation in microvascular endothelial cells, and suppressed migration and invasion in tumor cells. Fv-LDM-NGR interfered with the intracellular signaling transduction pathways, then caused G2/M and S phase arrest and induced apoptosis. CONCLUSION :Bispecific antibody-drug conjugate Fv-LDM-NGR could prevent cell invasion in tumor cells and tube formation in microvascular endothelial cells through blocking activity of CD13. And it could down-regulate the expression and the phosphorylation of EGFR, interfere with cellular signal pathways, induce cell cycle arrest and cell apoptosis, and inhibit cell proliferation and migration.
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Previously developed Asn-Gly-Arg (NGR) peptide-modified multifunctional poly(ethyleneimine)-poly(ethylene glycol) (PEI-PEG)-based nanoparticles (TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin (DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells (HUVEC) to better understand the cellular entry mechanism. In the present investigation, experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13 (APN/CD13) and caveolin 1 (CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment, TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl--eyclodextfin (MCD), further identifying the involvement of caveolae-mediated endocytosis (CvME). This conclusion was also verified by endocytosis inhibitor experiments.
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Liver cancer stem cells (LCSC)play the critical role in hepatocellular carcinoma development and maintenance. They are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. LCSC associate closely with tumor resistance to chemo/radiation therapy , tumor relapse and metastasis, and can be identified and separated with some special surface markers from hepatocellular carcinoma, such as CD133, CD90, CD44, CD24 and EpCAM to investigate the biological behaviors of them. Early studies showed that these markers can be regarded as special surface markers of liver cancer stem cells. Recent studies found that aminopeptidase N (APN,CD13+)cells in hepatocellular carcinoma have biological characteristics of stem cells and demonstrated that CD13 is a marker for semiquiescent CSC in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. In this review,we introduce the structure and the main function of CD13,liver cancer stem cells source and identification,CD13 + CSC in hepatocellular carcinoma and combination therapy in the treatment of liver cancer.
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Liver cancer stem cells (LCSC) play the critical role in hepatocellular carcinoma development and maintenance. They are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. LCSC associate closely with tumor resistance to chemo/radiation therapy, tumor relapse and metastasis, and can be identified and separated with some special surface markers from hepatocellular carcinoma, such as CD133, CD90, CD44, CD24 and EpCAM to investigate the biological behaviors of them. Early studies showed that these markers can be regarded as special surface markers of liver cancer stem cells. Recent studies found that aminopeptidase N (APN, CD13+) cells in hepatocellular carcinoma have biological characteristics of stem cells and demonstrated that CD13 is a marker for semiquiescent CSC in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. In this review, we introduce the structure and the main function of CD13, liver cancer stem cells source and identification, CD13+ CSC in hepatocellular carcinoma and combination therapy in the treatment of liver cancer.
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Objective To investigate the expressions of the CD13 in gastric cancer and the relationships between it and the patients' prognosis.Methods The expressions of CD13 were detected by immunohistochemical (SP method) in 104 cases of gastric cancer and 16 cases of normal gastric mucosa.Results The expressions of CD13 in 104 cases of gastric carcinoma and 16 cases of normal gastric mucosa show positive rate were 74％ (77/104) and 0％,respectively.The expressions of CD13 in gastric cancer were higher than in normal gastric mucosa and the difference was statistically significant (P ＜ 0.01).The expressions of CD13 in gastric cancer were not relative to patients' age,gender,and lymph node metastasis (P ＞ 0.05),but to be correlative with tumor sizes,clinical stage,degree of differentiation,and patients' 5-year survival rate (P ＜ 0.05).Conclusions The abnormal expression of CD13 in the gastric cancer may be correlative with the occurrence and development of gastric cancer,which can be an important indicator to evaluate the degree of malignance,guide treatment and assess uncertain prognosis of gastric cancer.
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Aminopeptidase N,a zinc-dependent exopeptidase,is highly expressed in many kinds of tumors,which involves in the degradation of extracellular matrix barriers and angiogenesis and promotes the invasion and metastasis of cancer cells.Aminopeptidase N inhibitors can induce apoptosis and inhibit the invasion and metastasis of tumor cells,which has become an attractive target for anti-tumor therapy.
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Objective To study aminopeptidase N/CD13 expression in hepatocellular carcinoma and its relationship with clinical data and proguosis in patients with hepatocellular carcinoma.Methods The immunohistochemical SP method was used to detect the CD13 monoclonal antibody in 40 cases of hepatocellular carcinoma,10 cases of corresponding para-carcinoma and 10 cases of cavernous hemangioma.Results Forty cases ( 100％ ) hepatocellular carcinoma tissues were seen varying degrees of CD13 expression,3 (30％) corresponding para-carcinoma tissues were weakly positive,and 10 cases of cavernous hemangioma with no expression.The expression rate of CD13 was not significantly correlated with the patient gender,age,serum AFP value,HbsAg,differentiation,CHILD grade and TNM stage (P＞0.05).But the expression of CD13 was closely related with the patient serum AFP value,HbsAg,differentiation ( P ＜ 0.05 ).By the survival function graph we could find the expression rate was negativly correlated with survival in patients,but the expression was not significantly correlated with tumor relapse.Conclusion CD13 can be used as the surface marker of liver cancer stem cells,and it is expected to become an effective indicator of prognosis in patients with hepatocellular carcinoma.
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Objective: To observe the inhibitory effects of matrine, oxymatrine and sophordine on expression of CD91 and CD13 and secretion of TNF-α in macrophage RAW264.7. Methods: Macrophages were cultured in 6-hole plate and coverslip was prepared. Then macropages were cultured one day with different concentrations(0,12. 5,25,50,100,200 mg/L) of matrine, oxymatrine and sophordine; the expression of CD91 and CD13 by immunohistochemical dyeing was analyzed by Image-Pro plus system (Media Cybemetic, Inc. , 6.0 edition). Meanwhile, the levels of TNF-α in the culture medium of macrophages were examined by ELISA. Results: Matrine, oxymatrine and sophordine could all inhibit CD91 and CD13 expression in macrophage RAW264.7, and the inhibition varied with the concentrations of matrine, oxymatrine and sophordine; the inhibitory effect of matrine was the most prominent one. Moreover, matrine, oxymatrine and sophordine also inhibited the secretion of TNF-α. Conclusion: Matrine, oxymatrine and sophordine can greatly inhibit expression of CD91 and CD13 and secretion of TNF-α in macrophage RAW264.7.
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This study was designed to investigate the expression of aminopeptidase N (APN)/CD13 on intraembryonic AGM stromal cells, and the change of its enzymatic activity after irradiation injury.The expression of APN/CD13 on AGM stromal cells was assayed by RT-PCR and immunihistochemistry. After the stromal cells in AGM region were irradiated with 8.0 Gy of 60Co γ-rays, APN/CD13 enzymatic activity was measured by spectrophotometer at different time points. The result showed that AGM stromal cells strongly expressed APN/CD13. The enzymatic activity of APN/CD13 decreased temporarily after irradiation injury, then increased to higher level 4 h after irradiation, and it returned to the pre-irradiation level 24 to 48 h after the irradiation. The enzymatic activity of APN/CD13 was temporarily enhanced after irradiation injury, which might be one of the compensatory mechanisms that promote the hematopoietic recovery after irradiation.
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BACKGROUND: The hemopoietic stem cells increase in number during the regeneration after chemotherapy or bone marrow transplantation (BMT). Although the proportion of hemopoietic stem cells and their differentiation have been studied by immunophenotyping using the flow cytometry, no substantial research efforts have been directed toward the regenerating marrow. We attempted to discover the proportions of undifferentiated stem cells, committed stem cells, B cell precursors, and myeloid precursors in the regenerating bone marrows during complete remission (CR) and after engraftment of BMT. METHODS: Bone marrow samples from 82 patients with acute leukemia in CR and from 25 patients after BMT engraftment, along with 22 control samples, were used to find the numbers of CD38-/CD34+, CD38+/CD34+, CD19+/CD34+, and CD13,33+/CD34+ cells in the large lymphocyte gate by flow cytometry. We cross-analyzed our results in terms of groups: CR, BMT, and initial diagnosis groups. We performed significance tests on age, relapse, chromosomal abnormalities, clinical outcomes, and initial immunophenotypes of the leukemic cells. RESULTS: The proportions of CD38-/CD34+, CD38+/CD34+, CD19+/CD34+, and CD13,33+/CD34+ cells are more highly distributed in acute B-lymphoblastic leukemia than the normal group and also in the CR than the BMT group. CD19+/CD34+ cells were increased in the relapse group and CD38+/ CD34+, CD19+/CD34+, and CD13,33+/CD34+ cells were increased in the group with chromosomal abnormality. The results were irrelevant to the initial immunophenotype of the leukemic blasts. CONCLUSIONS: The increases of the markers spanned too widely to apply one specific cutoff value to analyze them. They seemed to be the results of normal regeneration, irrelevant to relapse or initial immunophenotype of leukemic blasts.
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Humans , Acute Disease , Antigens, CD19/metabolism , Antigens, CD34/metabolism , ADP-ribosyl Cyclase 1/metabolism , Bone Marrow/physiology , Bone Marrow Transplantation , Flow Cytometry , Follow-Up Studies , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cells/immunology , Immunophenotyping , Leukemia/drug therapy , Regeneration , Remission InductionABSTRACT
BACKGROUND: Acute promyelocytic leukemia (APL) has two subtypes, a typical French-American-British (FAB)-M3 type and an atypical FAB-M3v type described as microgranular variant, and immunophenotyping is a rapid and accurate method for the diagnosis of APL. We tried to define immunological criteria for the diagnosis of APL in each different period from 1987 to 2003. The purpose of this study was to compare the discrimination capacity of several panels with FAB classification. METHODS: We applied immunophenotyping panel I, II, and III for the diagnosis of APL in each of the following three different periods: Panel I [HLA-DR(-), CD15(-)] (1987-1991); Panel II [HLA-DR(-), CD13(+), CD33(+), CD14(-)] (1992-1994); and Panel III [HLA- DR(-), CD34(-), CD13(+), CD33(+), CD14(-)] (1994-2003) with negative lymphoid markers in all panels. Standard FAB classification and direct immunofluorescence method were applied to diagnosis in 570 cases of acute leukemia. RESULTS: The immunophenotyping to identify FAB subtype AML-M3 and M3v was established as the panel of [HLA-DR (-), CD34 (-), CD13 and/or CD33 (+), CD14 (-)] with negative lymphoid markers (CD19, CD10, CD20, CD22, CD3, CD5, and CD7). The sensitivity and specificity of this panel for the diagnosis of APL was 100% and 99%, respectively. CONCLUSIONS: Our study demonstrates the evolution of immunophenotyping panel from a primitive to advanced design. This immunophenotyping panel can be a "quick reference" for the diagnosis of APL without extra effort.
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Classification , Diagnosis , Discrimination, Psychological , Fluorescent Antibody Technique, Direct , HLA-DR Antigens , Immunophenotyping , Leukemia , Leukemia, Promyelocytic, Acute , Sensitivity and SpecificityABSTRACT
We introduce an unusual case of acute myeloid leukemia (AML) showing strong myeloperoxidase (MPO) positivity without any lineage-specific cell surface marker expression, i.e. myelomonocytic antigens CD13, CD14, CD15 and CD33; or B-lymphoid antigens CD10, CD19, CD20, CD22 and surface immunoglobulin; or T-lymphoid antigens CD2, CD3, CD5 and CD7. The case was morphologically AML with maturation (FAB M2) and the cytogenetic study showed t (8; 21) (q22; q22) and missing Y. But Immunophenotypic studies by flow cytometry showed positive reaction ony for CD34 and HLA-DR. We considered this case as a 'presence of t (8; 21) in MPO (+), CD antigen (-) AML'. The myeloid lineage antigens are known to be expressed very early during myeloid differentiation whereas MPO (in its functional form) is viewed as being expressed relatively late in the process. Therefore, this case could be an example of 'asynchronous differentiation' in leukemia.