• Title/Summary/Keyword: differentiation therapy

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The Effect of External Radiation Therapy in Management of Malignant Obstructive Jaundice due to Porta Hepatis Metastasis from Stomach Cancer (위암의 간문맥 전이로 발생한 악성 폐쇄성 황달에 대한 외부 방사선치료 효과)

  • Yang, Kwang-Mo;Kim, Joon-Hee;Kim, Chul-Soo;Suh, Hyun-Suk;Kim, Re-Hwe
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.339-348
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    • 1995
  • Purpose : Since 1983, authors have conducted a study to evaluate the effect of external radiation therapy and to determine affected factors in management of the patients with malignant obstructive jaundice due to porta hepatis metastasis from stomach cancer. Materials and Methods : Thirty two patients with malignant obstructive jaundice due to porta hepatis metastasis from gastric cancer were presented. We have analysed 23 patients who were treated with external radiation therapy of more than 3000cGy. The radiation dose, disease extent at developement of jaundice, total bilirubin levels before radiation therapy, differentiation of histology, combind treatment, intent of primary surgery, initial stage of gastric cancer were analyzed to determine affected factors in radiation therapy. External radiation therapy was delivered with a daily dose of 180-300cGy, 5 times a week fractionation using 4 MeV linear accelerator. The radiation field included the porta hepatis with tumor mass by the abdominal ultrasonography or CT scan. In twenty three patients received more than 3000cGy, total irradiation dose was ranged from 3000cGy to 5480cGy, median 3770cGy. Among 23 patients, 13 patients were delivered more than equivalant dose of TDF 65(4140cGy/23fx). Results : Among 23 patients, complete, partial and no response were observed in 13, 5, 5 patients, respectively. The median survival for all patients was 5 momths. The significant prolongation of median survival was observed in complete responders(11 months) as compared to partial and no responders(5 months, 5 months respectively) Out of 13 patients with complete response, 6 patients lived more than a year Among 13 patients receiving more than 4140cGy equivalent dose, complete, partial and no response were observed in 10, 2 and 1 patients, respectively. The median survival for all these patients was 9.5 months. The median survival for complete responders(10/13) was 11.5 months. Among 10 patients receiving less than 4140cGy equivalent dose, complete, partial and no response were observed in 3, 3, 4 patients, respetively. The median survival for all these patients was 4.3 months Therefore, the radiation dose affected the results of treatment. For the complete response with prolongation of survival duration, at least 4140cGy equivalant dose should be delivered to porta hepatis. In evaluation of the disease extent, 7 patients of 13 complete responders showed localized disease in porta hepatis or peripancreatic area, but all patients with partial and no response showed wide extensive disease or persistant disease of primary gastric cancer. Therefore. the patients with the localized disease were the higher probability of complete response and long term survival. This study suggested that the radiation dose and the disease extent at developement of jaundice affected in radiation therapy for malignant obstructive jaundice. There were no serious complications related to external radiation therapy. Conclusion : External radiation therapy only could achieve the palliative effect in the patients with malignant obstructive jaundice due to porta hepatis metastasis from stomach cancer. This study suggested that the prolongation of survival duration could be achived in complete responders and radiation dose, extent of disease affected the results of treatment of malignant obstructive jaundice.

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Prognostic Significance of Beclin-1 Expression in Colorectal Cancer: a Meta-analysis

  • Han, Ye;Xue, Xiao-Feng;Shen, Hu-Gang;Guo, Xiao-Bo;Wang, Xu;Yuan, Bin;Guo, Xing-Po;Kuang, Yu-Ting;Zhi, Qiao-Ming;Zhao, Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4583-4587
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    • 2014
  • Objective: Beclin-1 has recently been observed as an essential marker of autophagy in several cancers. However, the prognostic role of Beclin-1 in colorectal neoplasia remains controversial. Our study aimed to evaluate the potential association between Beclin-1 expression and the outcome of colorectal cancer patients. Materials and Methods: All related studies were systematically searched in Pubmed, Embase, Springer and Chinese National Knowledge Infrastructure databases (CNKI), and then a meta-analysis was performed to determine the association of Beclin-1 expression with clinical outcomes. Finally, a total of 6 articles were included in our analysis. Results: Our data showed that high Beclin-1 expression in patients with CRC was associated with poor prognosis in terms of tumor distant metastasis (OR=2.090, 95%CI=1.061-4.119, p=0.033) and overall survival (RR=1.422, 95%CI=1.032-1.959, p=0.031). However, we did not found any correlation between Beclin-1 over-expression and tumor differentiation (OR=1.711, 95%CI=0.920-3.183, p=0.090). In addition, there was no evidence of publication bias as suggested by Egger's tests for tumor distant metastasis (p=1.000), differentiation (p=1.000) and OS (p=0.308). Conclusions: Our present meta-analysis indicated that elevated Beclin-1 expression iss associated with tumor metastasis and a poor prognosis in patients with CRC. Beclin-1 might serve as an efficient prognostic indicator in CRC, and could be a new molecular target in CRC therapy.

Expression of Ang-2/Tie-2 and PI3K/AKT in Colorectal Cancer

  • Zhang, Ji-Hong;Wang, Li-Hua;Li, Xiang-Jun;Wang, Ai-Ping;Reng, Li-Qun;Xia, Feng-Guo;Yang, Zhi-Ping;Jiang, Jing;Wang, Xiao-Dan;Wen, Chun-Yang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8651-8656
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    • 2014
  • Purpose: To study the expression of angiogenin-2 (Ang-2) and its receptor Tie-2 in colorectal cancer and discuss the possible mechanisms behind this process. Materials and Methods: Using the streptavidin-peroxidase (SP) immunohistochemical method, paraffin sections from 100 colorectal cancer samples and 10 samples from tumor-adjacent normal tissue (> 2 cm from the edge of the gross tumor) were tested for protein expression of Ang-2, Tie-2, PI3K, and AKT. Reverse transcription-polymerase chain reaction and Western blots were further used to measure expression of the 4 genes and proteins in 20 freshly-resected colorectal cancer samples and tumor-adjacent normal tissues. Results: In colorectal cancer tissues, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins was significantly higher than in tumor-adjacent normal tissues. Protein expression in poorly-differentiated adenocarcinoma was higher than that in well and moderately differentiated adenocarcinoma. According to Duke's classification, the protein expression in Stages C and D was significantly higher than that in Stages A and B. In the group with lymphatic metastasis, the protein expression was higher than that without lymphatic metastasis. Conclusions: In colorectal cancer, the expression of the Ang-2, Tie-2, PI3K, and AKT genes and their proteins is markedly higher than those in tumor-adjacent normal tissues. No correlation was observed between protein expression and gender, location, or histologic type. Correlations did exist between protein expression and differentiation level, stage of Duke's classification, and lymphatic metastasis; in colorectal cancer tissues with lower differentiation levels, higher stages of Duke's classification, and lymphatic metastasis, the expression of all 4 proteins was higher. The study of their expression patterns and relationships with aggression and metastasis will provide a valuable experimental foundation for assessing prognosis and targeted therapy of colorectal cancer.

Beyond the Molecular Facilitator, CD82: Roles in Metastasis Suppressor, Stem Cell Niche, Muscle Regeneration, and Angiogenesis (분자 촉진제를 넘어, CD82: 전이억제자, 줄기세포 니쉬, 근육 재생 및 혈관신생에서의 역할)

  • Lee, Hyun-Chae;Han, Jung-Hwa;Hur, Jin
    • Journal of Life Science
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    • v.31 no.9
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    • pp.856-861
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    • 2021
  • CD82/KAI1, identified as a metastasis suppressor, was initially known only as a molecular facilitator, but its various functions have recently been revealed. CD82 plays an important role in the stem-progenitor cell, angiogenesis, and muscle. We would like to introduce the recently reported functions and roles of CD82 in this review. CD82 is a member of the tetraspanin family, which consists of four transmembrane domains. The interaction between CD82 and cell adhesion molecules suppresses the metastasis of cancer. CD82 regulates the cell cycle of stem-progenitor cells in the stem cell niche. In the bone marrow, CD82 is expressed on long-term repopulating hematopoietic stem cells (LT-HSCs), which show multipotent differentiation potential. The interaction between CD82 and Duffy antigen receptor for chemokines (DARC) induces quiescence in LT-HSCs. CD82 also regulates Rac1 activity, resulting in the homing and engraftment of HSCs into the bone marrow niche. Besides, CD82 maintains the differentiation potential of muscle stem cells and prevents angiogenesis by inhibiting the expression of cytokines, such as IL-6 and VEGF and adhesion molecules in endothelial cells. CD82 is a key membrane protein that distinguishes the hierarchy of stem-progenitor cells, and is also important for amplification and verification of cellular resources. Further studies on the function of CD82 in various organs and cells are expected to advance cell biology and cell therapy.

Dysfunctional pancreatic cells differentiated from induced pluripotent stem cells with mitochondrial DNA mutations

  • So, Seongjun;Lee, Song;Lee, Yeonmi;Han, Jongsuk;Kang, Soonsuk;Choi, Jiwan;Kim, Bitnara;Kim, Deokhoon;Yoo, Hyun-Ju;Shim, In-Kyong;Oh, Ju-Yun;Lee, Yu-Na;Kim, Song-Cheol;Kang, Eunju
    • BMB Reports
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    • v.55 no.9
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    • pp.453-458
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    • 2022
  • Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

EXPRESSION OF THE GENES OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VON WILLEBRAND FACTOR IN SALIVARY GLAND TUMORS (타액선 종양에서 혈관내피성장인자와 von Willebrand 인자 유전자 발현에 관한 연구)

  • Chung, Ji-Hun;Kim, Ji-Hyuk;Park, Young-Wook
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.1
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    • pp.41-51
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    • 2008
  • Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

Neurotransmitter and Neuroendocrine Markers as Predictors of Therapeutic Responses In Psychiatric Disorders (신경전달물질 및 신경내분비 Marker를 이용한 치료반응의 평가)

  • Han, Chang-Hwan
    • Korean Journal of Biological Psychiatry
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    • v.2 no.1
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    • pp.3-19
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    • 1995
  • Numerous investigators have conducted extensive investigation in the search for biological markers in psychiatric illness. There are, as a test of q biological approach to the diagnosis of the psychiatric illness, tests for the neurotransmitters, their metabolites, and related enzymes, the neurotransmitter receptors, the neuroendocrine output and response, the membrane transport, peptides and eletrolytes. They are called the biological markers, and they are helpful for the diagnosis or differential diagnosis, choice of treatment or drugs, symptom improvement, predictor of recurrence and anticipation of suicidal attempt. These studies are among the main purposes that are pursued in the neuroscience and based on the potential utility of the biological markers mentioned above. Since 1970's, lots 01 biological markers' studies for the diagnosis, differential diagnosis or subtypes differentiation have been done but varieties of different opinions have been drawn since then through they could explain the charaters of main psychiatric illness(especially schizophrenia and mood disorder). But, the search for biological markers, including displines of neuroendoclinology and neurochemistry(neurotransmitter and thair metabolite), has yielded a number of putative trait merkers and state markers for psychayric illness. This paper aims to anticipate or evaluate the good response to the therapy(Therpeutic response) with lots of markers. Acoording to the diagnosis of lots of diseases or subtypes, we are going to review the papers, mainly concern with 'Is there any Marker' or 'Is any test possible to detect the improvement clinically?' 'Is it possible to predict the recurrence or good prognsis?' or 'Is it possible to select any drug or therapy to bring the good response?' The biological tests to review are mainly the metabolites of catecholamine neurotransmitter, and especially neuroendocrine test based on the knowledge that hormons of the adenohypophysis are influenced by activity of the cerebral or limbic neurons as well as the hypothalamus ones. Among them, author introduced some clinically available tests that are DST, TRH stimulation test(TRHST), GH stimulation test, and the urine MHPG test that can give us the evaluation of the treatment response, the predictor for recurrence or choice of drug that can bring a good response. So author discussed thair potential utility in clarifying, therapeutic, and prognostic issues in psychatric illness. We hope they'll be used and look forward to more active study on the different opinion.

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The Clinical Study on 40 Cases of Patient with Chronic Prostatitis (만성전립선염환자(慢性前立腺炎患者) 40예(例)에 대(對)한 임상적(臨床的) 고찰(考察))

  • Cho, Chung Sik;Kim, Chul Jung
    • Journal of Haehwa Medicine
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    • v.8 no.2
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    • pp.245-257
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    • 2000
  • A clinical study was done 40 patients of chronic prostatitis who was treated in Dept. of Internal Medicine, Oriental Medicine Hospital, Taejon University, from 1 Mar. 1999 to 31 Oct. 1999. The results were as follows. 1. In distribution of age, 30's and 40's were 57.5% the most, 20's and 60's were 35.0%, 50's was 7.5%. 2. In distribution of past history, the urethritis(45.0%) was the most. 3. In distribution of ocupation, a white-collar worker was 35.0%, a business man was 22.5%, a public servant was 12.5%, etc. 4. Sitting the mean time of day were distributed 5~7 hours, above 7 hours, 3~5 hours, under 3 hours, etc. 5. The resting interval of a long distance drive were distributed 2 hours(35.0%), 3 hours(32.5%), etc. 6. The habit of enduring ejaculation during sexual intercourse was showed 45.0%. 7. The habit of enduring urination was showed 20.0%. 8. Influency of mental stress was showed 90.0%. 9. Ten cases(25.0%) were showed riding horse or riding bicycle. 10. Four cases(10.0%) were showed wearing tight trousers. 11. The habit of put a wallet his hip pocket was showed 57.5%. 12. The most common symptom was distributed the others symp-tom(66.8%) and the voiding symptom(63.3%) more than pain-neuro-logical symptom(37.5%) and symptom related with sexual function (26.6%). 13. In distribution of palpation, lower abdominal pain, lumbar pain, perineal or parascrotal pain were mostly showed right side. Moreover diagnosis of pulsation was weakly showed chi pulse of right. 14. Duration of disease were distributed above 1 year(82.5%), under 1 year(17.5%). Degree of prostatitis was severe showed adove 1 year. 15. The distribution of WBC count of the prostatic secretion, com-paring with before therapy and after therapy, were showed from 5 cases to 0 case in very many/HPF, from 23 cases to 13 cases in many/HPF, from 12 cases to 13 cases in 10~30/HPF, from 0 case to 13 cases in under 10/HPF. 16. Therapeutic improvement of symptom were distributed pain-neurological symptom(94.8%), the others symptom(90.8%), the void-ing symptom(89.6%) and symptom related with sexual function(67.5%). 17. Differentiation of symptoms and signs were distributed dificiency of spleen-lung vital energy, wetness-heat of lower warmer, dificiency of spleen-kidney yang, dificiency of kidney yin, wetness-phlegm, dificiency of vital energy and blood. The prescriptions were Bojungikgitang(44.6%), Yukmijihwangtang(20.7%), Palmijihwangtang(12.0%), etc.

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Retinoid Receptors in Gastric Cancer: Expression and Influence on Prognosis

  • Hu, Kong-Wang;Chen, Fei-Hu;Ge, Jin-Fang;Cao, Li-Yu;Li, Hao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1809-1817
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    • 2012
  • Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

Efficient Gene Delivery into Hematopoietic Stem Cells by Intra-Bone Marrow Injection of Retrovirus (IBM 이식을 통한 골수 조혈 줄기 세포에의 효과적인 유전자 도입)

  • Lee, Byun-Joo;Lee, Yong-Soo;Kim, Hye-Sun;Kim, Yu-Kyung;Kim, Jae-Hwan;Park, Jin-Ki;Chung, Hak-Jae;Chang, Won-Kyong;Kim, Dong-Ku
    • Reproductive and Developmental Biology
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    • v.32 no.1
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    • pp.9-14
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    • 2008
  • Efficient gene transfer into hematopoietic stem cells is a great tool for gene therapy of hematopoietic disease. Retrovirus have been extensively used for gene delivery and gene therapy. However, current in vitro gene transfer has some obstacles suck as induction of differentiation loss of self-renewal capacity, and down-regulation of homing efficiency for in vitro hematopoietic stem cells transplantation. To overcome these problems, we developed efficient in vitro retroviral transfer technique by direct intra-bone marrow injection (IBM). We identified effective retrovirus gene transfer in bone marrow hematopoietic cells in vitro. Two weeks after retrovirus transfer via IBM injection, we observed stable EGFP gene expression in bone marrow, lymph node, spleen, and liver cells. In addition, $6.4{\pm}2.7%$ of hematopoietic stem/progenitor cells were expressed EGFP transgene from flow cytometry analysis. Our results demonstrate that in vitro retrovirus gene transfer via IBM injection can provide a viable alternative to current or moo gene transfer approach.