• Radiation Oncology Journal
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• v.13 no.2
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• pp.121-128
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• 1995

Purpose: The enhanced cytotoxic effect of combined treatment of hyper-thermia and chemotherapy by increasing intracellular acidity with HMA was investigated. Materials and Methods: FSall tumor cells were injected on the hindlegs of female $C_3H$ mice. When the tumor volume reached about 200mm3, experiments were performed on the groups classified as follows: Group I :Control, Group II : Melphalan alone (2.5mg/kg, 5mg/kg, 10mg/kg, 15mg/kg), Group III : Heat alone $(42.5^{\cdot}C$ for 1 hour) Group IV : Melphalan + Heat $(42.5^{\cdot}C$ for 1 hour), Group V : HMA(10mg/kg) + Melphalan(5.0mg/kg) + Heat$(42.5^{\cdot}C$ for 1hour). Each group included 8-12 mice on each experiment HMA (3-amino-6-chloro-5-(1-homopiperidyl )-N-(diaminomethylene) -c-pyrazinecarboxamide), an analog of amiloride which increases intracellular pH(pHi) was dissolved in dimethyl sulfoxide (DMS) and injected into the tumor-bearing mice through the tail vein. 10mg/kg of HMA and each dose of melphalan were injected into peritoneum of the tumor-bearing mice 30 minutes before heating. Tumor growth delay was calculated when the tumor volme reached at $1500mm^3$ Excision assay was performed on each group and repeated 2-4 times. Results : Tumor growth delay of each experimental groups at $1500mm^3$ were 9, 10, 13 and 19 days respectively. In vivo-in vitro excision assay using FSall tumor cells, the cytotoxicity of each experimental groups was $1.2{\times}10^7,\;1{\times}10^7,\;6{\times}10^6,\;1.7{\times}10^6\;and\;1{\times}10^5$ clonogenic cells/gm respectively When HMA was added to the combined treatment of heat and .chemotherapy, the tumor growth was delayed more than combined treatment without HMA i.e., 6 days tumor growth delay at $1500mm^3$ of tumor volume. Conclusion: The combined effect of cytotoxicity by heat and chemotherapy can be much more enhanced by HMA.

• Radiation Oncology Journal
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• v.21 no.3
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• pp.192-198
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• 2003

Purpose: Current results of autologous stem cell transplantation (SCT) suggest that this procedure may prolong disease free survival In patients with acute myeloid leukemia (AML). Autologous SCT is increasingly used as treatment for AML in first remission. The aim of this study was to evaluate the outcome of autologous SCT for patients with AML in first remission treated by autologous SCT using cytarabine, melphalan and total body irradiation (TBI) as the conditioning regimen. Materials and Methods: Between January 1995 and December 1999, 29 patients with AML in first remission underwent autologous SCT. The median age of patients was 33 years (range, 16 to 47). The conditioning regimen consisted of cytarabine ($3.0\;gm/m^2$ for 3 days), melphalan ($100\;gm/m^2$ for 1 day) and TBI (total 1000 cGy in five fractions over 3 days). Results: The median follow up was 40 months with a range of 3 to 58 months. The 4-year cumulative probability of disease free survival was 69.0%, and median survival was 41.5 months. The 4-year relapse rate was 27.6%. The factor Influencing disease free survival and relapse rate was the French-American-British (FAB) classification ($M_3$ group vs. other groups; p=0.048, p=0.043). One patient died from treatment-related toxicity. Conclusion:: Although the small number of patients does not allow us to draw any firm conclusion, our results were encouraging and suggest that the association of cytarabine, melphalan and TBI as a conditioning regimen for autologous SCT for AML on first remission appears to be safe and effective.

• Environmental Analysis Health and Toxicology
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• v.23 no.1
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• pp.23-32
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• 2008

In the present study, ROS detection of L5178Y cells that were treated with twenty test compounds in order to find out hydrogen peroxide ($H_2O_2$) induction for genotoxicity and carcinogenic toxicity. Twenty test compounds were consist of four classes, such as genotoxic carcinogens, genotoxic noncarcinogens, nongenotoxic carcinogens, and nongenotoxic noncarcinogens. Genotoxic carcinogens are 1,2-dibromoethane, glycidol, melphalan, diethylstilbestrol and urethane. Genotoxic noncarcinogens are 8-hydroxyquinoline, emodin, acetonitrile and diallylphthalate, L-ascorbic acid. Nongenotoxic carcinogens are methyl carbamate, O-nitrotoluene, 1,4-dioxane, tetrachloroethylene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. And nongenotoxic noncarcinogens are D-mannitol, 1,2-dichlorobenzene, caprolactam, bisphenol A and chlorpheniramine maleate.

• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.664-669
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• 2004

Extramedullary plasmacytoma(EMP) comprises 5% of all plasma cell neoplasms and commonly occurs in the upper airway or digestive tract. However, it rarely develops in the lungs. We present a case of primary pulmonary plasmacyotma in a 45 year old man, who presented as an endobronchial mass with a pleural effusion, but without evidence of multiple myeloma. The treatment options for EMP include surgery, surgery and radiotherapy, surgery and chemotherapy or chemotherapy alone. Surgery and radiation therapy appeared to be equally effective forms of treatment. The local recurrence rate was reported to be 30%, with 48% progressing to multiple myeloma, and median survival was reported to be 63-101 months. Our patient was initially treated with melphalan and prednisolone. However the disease progressed, and radiotherapy was combined with chemotherapy. In addition, the chemotherapy regimen was also changed to thalidomide and dexamethasone. The patient did not respond to this treatment regimen and finally died.

• Molecules and Cells
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• v.39 no.12
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• pp.898-908
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• 2016

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.

• Journal of Yeungnam Medical Science
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• v.35 no.1
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• pp.76-83
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• 2018

Background: Elderly patients with multiple myeloma (MM) are vulnerable to adverse events (AEs). This study evaluated adherence to chemotherapy and treatment outcomes in elderly patients treated with a frontline bortezomib (BTZ), melphalan, and prednisone (VMP) regimen and regimens without BTZ. Methods: One-hundred and forty elderly patients who were diagnosed with MM from March 2007 to March 2015 were included in this retrospective study. To evaluate regimen adherence, patients who were treated with more than 4 cycles were assigned to the good adherence group. Results: Among the 140 patients, 71 were treated with a frontline VMP and 69 with non-BTZ regimens. The median age was 71 years (range, 65-90 years). The VMP group showed a higher complete response rate than the non-BTZ group: 26.8% vs. 7.2%. More patients in the VMP group achieved ${\geq}$very good partial response (VGPR) and ${\geq}PR$. In the VMP group, 27 patients (38.0%) received less than 4 cycles. The VMP good adherence group showed a higher 3-year overall survival (OS) rate (70.9%) than the poor adherence group (60.2%, p=0.059). In the multivariate analysis, treatment with ${\geq}4$ cycles of VMP was a favorable factor for OS. Conclusion: A good adherence to a frontline VMP regimen resulted in favorable long-term survival. Adequate management of AEs will be needed to achieve favorable outcomes in elderly patients with MM.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.77-89
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• 1999

Background: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. Methods: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. Results: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, and cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/$m^2$ and that of cyclophosphsmide was 6,000 mg/$m^2$. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. Conclusion: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be bel1eficial in some cases.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.370-375
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• 2002

Purpose : In most cases, myelodysplastic syndrome(MDS) transforms into a more aggressive state or acute myelogenous leukemia; it's prognosis is very poor. It is believed that hematopoietic stem cell transplantation(HSCT) is the only curative treatment of MDS, but available data in children are very sparse. In this report, the short term outcome of HSCT in childhood MDS was analyzed. Methods : Ten children with MDS(CMMoL 5, RAEB 3, RAEBt 2) underwent HSCT(HLA-matched sibling transplantation 4, HLA-matched unrelated transplantation 4, cord blood transplantation 1, HLA-mismatched familial transplantation 1) between November 1995 and January 2001 at St. Mary's Hospital. Median follow-up duration was 11 months. Results : Engraftment was successful in all cases and 8 patients are alive without disease. Three cases of VOD were observed and improved without complication. Four cases of grade II and 1 case of grade III acute GVHD were observed and well controlled with treatment. Three patients relapsed after transplantation. One patient is alive without disease after cytoreduction with allogenic stem cell rescue and 2 patients died of relapse. Conclusion : HSCT is a curative strategy of MDS and the survival rate is relatively higher than that of adults. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.

• Clinical and Experimental Pediatrics
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• v.49 no.12
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• pp.1329-1339
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• 2006

Purpose : Failure of hematopoietic stem cell transplantation(HSCT) may be encountered in practice because of either relapse of the malignancy or dysfunction of the graft. Second HSCT may be the only option for some patients whose initial HSCT failed. Methods : From May, 1991 to December, 2004, 115 HSCTs were performed at the Pediatric Blood & Marrow Transplantation Center, Chonnam National University. This study was a retrospective analysis of the medical records of 15 patients who received the second HSCT after initial graft. Results : Among eight patients with nonmalignant diseases, two patients underwent the second HSCT because of primary graft failure and five because of late graft rejection. The remaining Fanconi anemia patient was re-transplanted due to development of AML. Two patients died and one experienced primary graft failure, but is still alive. The Kaplan-Meier 5-year overall survival rate was 75 percent and the disease free survival rate was 62.5 percent in nonmalignant diseases. All malignant patients underwent second transplants because of relapses. Four died of relapse and one of treatment-related complications. The Kaplan-Meier 2-year overall and event free survival rate was 28.6 percent each in malignant diseases. Conclusion : Second HSCT for graft dysfunction of nonmalignant disease seems to be feasible and should be considered as a standard practice. The relapse of malignant diseases remains a big obstacle even after the second HSCT, although a small portion of patients might be salvaged. Further investigation of novel therapeutic strategies, as well an the understanding of the biology should be explored.