Child ; Child, Preschool ; Drug Therapy ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Remission Induction ; methods ; Survival Analysis ; Treatment Outcome

Central Nervous System ; pathology ; Central Nervous System Neoplasms ; drug therapy ; Child ; Child, Preschool ; Humans ; Methotrexate ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

Child ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy

Child ; Graft Survival ; HLA Antigens ; genetics ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Polymerase Chain Reaction ; Tissue Donors ; Transplantation Chimera ; genetics ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; immunology

Severe acute respiratory syndrome (SARS) has recently recognized as a new human infectious disease. A novel coronavirus was identified as the causative agent of SARS. This report summarizes the hematological findings in SARS patients and proposes a hypothesis for the pathophysiology of SARS coronavirus related abnormal hematopoiesis. Hematological changes in patients with SARS were common and included lymphopenia (68% - 90% of adults; 100% of children, n = 10), thrombocytopenia (20% - 45% of adults, 50% of children), and leukopenia (20% - 34% of adults, 70% of children). The possible mechanisms of this coronavirus on blood system may include (1) directly infect blood cells and bone marrow stromal cells via CD13 or CD66a; and/or (2) induce auto-antibodies and immune complexes to damage these cells. In addition, lung damage in SARS patients may also play a role on inducing thrombocytopenia by (1) increasing the consumption of platelets/megakaryocytes; and/or (2) reducing the production of platelets in the lungs. Since the most common hematological changes in SARS patients were lymphopenia and immunodeficiency. We postulate that hematopoietic growth factors such as G-CSF, by mobilizing endogenous blood stem cells and endogenous cytokines, could become a hematological treatment for SARS patients, which may enhance the immune system against these virus.
Adult ; Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; CD13 Antigens ; immunology ; Cell Adhesion Molecules ; Child ; Hematologic Diseases ; immunology ; physiopathology ; Hematopoiesis ; physiology ; Humans ; SARS Virus ; Severe Acute Respiratory Syndrome ; immunology ; physiopathology ; virology

The immunological role of megakaryocytes is not well known. This project studies the involvement of megakaryocytes on immuno-inflammatory processes and the possible mechanism via the adhesion molecule CD36 and the synthesis of relevant cytokines. The expression of adhesion protein CD36 on human platelets, megakaryocytes and megakaryocytic cell lines (Meg-01, Dami, CHRF-288-11 and M-07e) was analyzed by using flow cytometry, ELISA and immunocytochemical methods. The expression of interleukin-1 (IL-1) to interleukin-10 (IL-10), TNF-alpha, TNF-gamma and IFN-gamma on the four megakaryocytic cell lines was also determined by RT-PCR. The effect of IL-1beta, IL-3, IL-6 and TPO on murine megakaryocyte colony formation (CFU-MK) was studied by using a plasma clot culture system. The CFU-MK was confirmed by acetylcholine esterase staining. The results showed that: (1) CD36 was expressed on platelets, megakaryocytes and the four megakaryocytic cell lines, the relative expression level is as follows: platelets > megakaryocytes > Meg-01 > Dami > CHRF-288-11 > M-07e, suggesting that the level of CD36 expression correlates with the degree of maturity of megakaryocytic differentiation; (2) inflammatory cytokines TNF-alpha, IL-1beta, IL-3 and IL-6 were detected in all the four megakaryocytic cell lines, suggesting that different stages of megakaryocytes can be as a source of inflammatory cytokines; and (3) IL-1beta, IL-3 and IL-6, as well as TPO, play a stimulating effect on CFU-MK formation, suggesting that there is an "autocrine" effect on megakaryocytopoiesis. The data obtained suggest that megakaryocytes may involve in immuno-inflammatory processes via the synthesis of platelet adhesion molecules and inflammatory cytokines.

The aim of this study was to investigate the effect of human bone marrow mesenchymal stem cells on human T-cell proliferation resulted from stimulation with PHA and possible immunomodulating mechanism. T cells were positively selected by CD3(+) magnetic beads, and were then co-cultured with irradiated MSCs overnight before the addition of PHA. T-cell proliferation was measured by BrdU assay and the degree of apoptosis was assessed by flow cytometry with Annexin V/PI. T cells co-cultured with or without MSCs were treated with PHA for 72 hours, then harvested. They were labeled with anti-CD4, anti-CD8, anti-CD25 antibodies and analyzed by flow cytometry. The results showed that MSCs inhibited T-cell proliferation, but did not induce T cell apoptosis. There were no significant changes in the ratio of CD4(+) and CD8(+) T cells of MSC-treated group, as compared with the control group. After stimulation with PHA, there was an increase in CD4(+) T cells and decrease of CD4(+)CD25(+) cells in MSC co-cultured group. It is concluded that the MSCs inhibit T-cell proliferation after stimulation with PHA, and show more inhibitive effects on CD8(+) and CD4(+) T cells, but CD25(+) regulatory T cells may not be involved in this process.
Bone Marrow Cells ; cytology ; CD4-CD8 Ratio ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Humans ; Mesenchymal Stromal Cells ; cytology ; physiology ; T-Lymphocyte Subsets ; cytology

Adolescent and young adult (AYA) with cancers have distinct spectrum of cancers as compared to younger and older age groups. The definition of age limits of AYA varies among countries, from 15-25 years to 12-39 years. The differences in age definition lead to variation in report of incidence, types of cancers and survival. In younger AYA patients, hematological malignancies are leading cause of cancers. In older AYA patients, testicular cancers are common in males while breast cancers and cervical cancers are predominant types in females. There is increasing incidence of AYA cancers worldwide in the past two decades. Overall survival and treatment outcome of AYA cancer has been improving in the last few decades. Specialized centers for AYA with cancers provide more comprehensive care and have been reported to have superior outcome. About 80% of AYA with cancers survive at 5 years after diagnosis but they are higher risk of developing second malignancies. Barriers to AYA cancer treatment included social economic status, insurance system and accessibility to clinical trials. Survivors of AYA cancers are also at higher risk dying from cardiovascular diseases and respiratory diseases. Survivorship program should be in place to enhance education and surveillance.

Adolescent and young adult (AYA) with cancers have distinct spectrum of cancers as compared to younger and older age groups. The definition of age limits of AYA varies among countries, from 15-25 years to 12-39 years. The differences in age definition lead to variation in report of incidence, types of cancers and survival. In younger AYA patients, hematological malignancies are leading cause of cancers. In older AYA patients, testicular cancers are common in males while breast cancers and cervical cancers are predominant types in females. There is increasing incidence of AYA cancers worldwide in the past two decades. Overall survival and treatment outcome of AYA cancer has been improving in the last few decades. Specialized centers for AYA with cancers provide more comprehensive care and have been reported to have superior outcome. About 80% of AYA with cancers survive at 5 years after diagnosis but they are higher risk of developing second malignancies. Barriers to AYA cancer treatment included social economic status, insurance system and accessibility to clinical trials. Survivors of AYA cancers are also at higher risk dying from cardiovascular diseases and respiratory diseases. Survivorship program should be in place to enhance education and surveillance.

To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.
Animals ; Apoptosis ; drug effects ; Brain Chemistry ; Cell Line ; Cell Proliferation ; drug effects ; Erythropoietin ; pharmacology ; Humans ; Mice ; Neoplasm Proteins ; analysis ; Neurons ; drug effects ; Oncogene Proteins ; analysis ; Proto-Oncogene Proteins ; analysis ; Receptors, Cytokine ; analysis ; Receptors, Thrombopoietin ; Thrombopoietin ; pharmacology