• Biomedical Science Letters
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• v.21 no.2
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• pp.51-59
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• 2015

A humanized mice (hu-mice) model is extremely valuable to verify human cell activity in vivo condition and is regarded as an important tool in examining multimodal therapies and drug screening in tumor biology. Moreover, hu-mice models that simply received human $CD34^+$ blood cells and tissue transplants are also overwhelmingly useful in immunology and stem cell biology. Because generated hu-mice harboring a human immune system have displayed phenotype of human $CD45^+$ hematopoietic cells and when played partly with functional immune network, it could be used to evaluate human cell properties in vivo. Although the hu-mice model does not completely recapitulate human condition, it is a key methodological factor in studying human hematological malignancies with impaired immune cells. Also, an advanced humanized leukemic mice (hu-leukemic-mice) model has been developed by improving immunodeficient mice. In this review, we briefly described the history of development on immunodeficient SCID strain mice for hu-and hu-leukemic-mice model for immunologic and tumor microenviromental study while inferring the potential benefits of hu-leukemic-mice in cancer biology.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.6-12
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• 2005

In the last few years, a spectrum of dendritic cells(DCs), including toll like receptors(TLRs), might play a critical role in regulating allergy and asthma. DC plays a central role in initiating immune responses, linking innate and adaptive responses to pathogen. Human peripheral blood has three non-overlapping dendritic subset that expressed various 11 TLRs. These dendritic subsets and TLR contribute significant polarizing influences on T helper differentiation, but how this comes about is less clear. A better understanding of DC immunobiology may lead to the comprehension of allergy pathophysiology to prevent early stage allergic march.

• Development and Reproduction
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• v.23 no.2
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• pp.79-92
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• 2019

Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• Journal of Chest Surgery
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• v.13 no.3
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• pp.306-311
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• 1980

Pure red cell aplasia is unusual cause of anemia and a selective aplastic disorder that affects the erythroid series of the bone marrow. Fifty percent of all patients with red cell aplasia will have a thymoma. Twenty-five to 30% of those who undergo thymectomy will be cured. A 57-years-old man was admitted to the medical department of Korea University hospital with complaints. Physical examination reveals a sick looking man with a pale lip, anemic conjunctiva and subicteric sclera. On auscultation, coarse breathing sound and moist rale was heard on the right lung field. Neither the liver nor spleen was palpable. A blood count showed the erythrocytes to number 2,640,000/mm3 and hemoglobin to be 7.0gm/dl. A white blood cell count was 5,000/mm3 and a platelet count was 328,000/mm3 Reticulocyte count was 0.7%. Examination of the peripheral blood smear showed the red cell, to be normocytic and normochromic. Urine sugar was three positive and GTT was positive. The anterior-posterior and lateral view of Chest X-ray was suggestive of an anterior mediastinal mass. A bone marrow biopsy reveals absence of red cell precursors and a normal myeloid series and megakaryocytes. At thoracotomy in May 1980 an encapsulated, lobulated, benign thymoma, which measured 5x7x5 cm was removed, microscopic examination showed it was of the spindle cell type. The postoperative course was uneventful, but the patient never had a return of hemoglobin to the blood. The patient was discharged on the postoperative] 3 days. At postoperative 1 month, the patient was readmitted for bone marrow study and had no return of red cells to bone marrow. At now, patient has been treated with steroid and the further follow up study will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.347-350
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• 2012

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (${\chi}^2$- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4699-4711
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• 2016

Background: In the last decade, it has become clear that change of gene expression may alter the hematopoietic cell quiescent state and consequently play a major role in leukemogenesis. WT1 is known to be a player in acute myeloid leukemia (AML) and FOXP3 has a crucial role in regulating the immune response. Objectives: To evaluate the impact of overexpression of WT1and FOXP3 genes on clinical course in adult and pediatric AML patients in Egypt. Patients and methods: Bone marrow and peripheral blood samples were obtained from 97 de novo non M3 AML patients (63 adult and 34 pediatric). Real-time quantitative PCR was used to detect overexpression WT1 and FOXP3 genes. Patient follow up ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the pediatric group; WT1 was significantly expressed with a high total leukocyte count median 50X109/L (p=0.018). In the adult group, WT1 had an adverse impact on complete remission induction, disease-free survival and overall survival (p=0.02, p=0.035, p=0.019 respectively). FOXP3 overexpression was associated with FAB subtypes AML M0 +M1 vs. M2, M4+M5 (p =0.039) and the presence of hepatomegaly (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverse impact on clinical presentation, treatment response and survival of pediatric and adult Egyptian AML patients.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.912-916
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• 2002

Cord blood is a useful source of allogeneic hematopoietic stem cells for bone marrow reconstitution. The number of umbilical cord blood transplants is increasing worldwide. In this a case 15-month-old boy with acute myeloid leukemia was treated with umbilical cord blood transplant from an HLA-3 loci mismatched unrelated donor. Granulocyte recovery greater than $500/mm^3$ occurred at day 49, and the platelet recovered greater than $20,000/mm^3$ independent of transfusion at day 81 after stem cell infusion.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.565-571
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• 2016

Paeoniflorin (PAE) is the most abundant compound in Xuebijing injection widely used to treat sepsis. We aimed to investigate effect of PAE on expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in a rat model of sepsis. Wistar rats were divided into Normal, Model, and PAE groups (n=20 each). Endotoxin was administrated at 5 mg/ml/kg in Model and PAE rats to establish rat sepsis model. 1 h after endotoxin administration, PAE was administrated at 4 ml/kg in PAE group once per day for 3 days. Routine blood tests and biochemical indexes were assessed, including aspartate aminotransferase (AST) and creatine kinase-MB (CK-MB). The plasma sTREM-1 level was measured using quantitative ELISA. At the end of experiment, the small intestine, liver, kidney and lung were subjected to pathological examinations. A rat model of sepsis-induced multiple organ dysfunction syndrome (MODS) was established successfully with endotoxin administration (5 mg/ml/kg), evidenced by histo-pathological examinations, routine blood tests and biochemical indexes: platelet count decreased and white blood cell count increased (p<0.05), CK-MB and AST increased (p<0.05). PAE treatment significantly reduced the plasma levels of AST, CK-MB, and sTREM-1, compared to Model group (p<0.05). Meanwhile, sepsis-induced damages in the liver, lung, stomach and intestinal mucosa were also markedly ameliorated by PAE treatment. PAE demonstrated a significantly protective effect in a rat model of sepsis by decreasing plasma sTREM-1 level, reducing inflammation, preventing MODS and protecting organ functions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1823-1829
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• 2014

Aims: Much evidence suggests that increased glucose metabolism in tumor cells might contribute to the development of acquired chemoresistance. However, the molecular mechanisms are not fully clear. Therefore, we investigated a possible correlation of mRNA expression of HIF-$1{\alpha}$ and GLUT1 with chemoresistance in acute myeloid leukemia (AML). Methods: Bone marrow samples were obtained from newly diagnosed and relapsed AML (M3 exclusion) cases. RNA interference with short hairpin RNA (shRNA) was used to stably silence GLUT1 or HIF-$1{\alpha}$ gene expression in an AML cell line and HIF-$1{\alpha}$ and GLUT1 mRNA expression was measured by real-time quantitative polymerase chain reaction assay (qPCR). Results: High levels of HIF-$1{\alpha}$ and GLUT1 were associated with poor responsiveness to chemotherapy in AML. Down-regulation of the expression of GLUT1 by RNA interference obviously sensitized drug-resistant HL-60/ADR cells to adriamycin (ADR) in vitro, comparable with RNA interference for the HIF-$1{\alpha}$ gene. Conclusions: Our data revealed that over-expression of HIF-$1{\alpha}$ and GLUT1 might play a role in the chemoresistance of AML. GLUT1 might be a potential target to reverse such drug resistance.