• Archives of Pharmacal Research
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• v.20 no.3
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• pp.259-263
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• 1997

In the preparation of acyclic thymidine nucleoside analogues, $K_2CO_3$(or NaH) treated thymine in DMSO was alkylated with .omega.-chloroalkyl nitrite (Cl-(CH_2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(${\omega}$-cyanoalkyl)thymine (2a-d) and 1,3-bis(${\omega}$-cyanoalkyl)thymine in approximately 5:1 ratios. Reduction of the cyano function 2a-d with $NaBH_{4}/CoCl_{2}$ center dot$ 6H_{2}O$gave the corresponding 1-(${\omega}$aminoalkyl)thymine (3a-d). The newly formed primary amino function in 3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[.omega.($N^{I}$-2-chloroethylureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-($ N^{I}-2$-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry $NaNO_{2}$-powder in anhydrous $CH_{2}Cl_{2}$gave two types of regioisomeric nitrosoureas, 1-[5-($N^{I}$--chloroethyl-$N^{I}$--nitrosoureido)pentylithymine (5d) and 1-[5-($N^{I}-2$-chloroethyl-N-nitrosoureido)pentyllthymine in approximately 5 :1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and 5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as $IC^{50}$ values. Compounds 3b and 4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.

• Archives of Plastic Surgery
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• v.38 no.5
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• pp.691-694
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• 2011

Purpose: With an increase in the population of immunocompromised patients, the incidence of maxillary sinus aspergillus infection has also escalated. Maxillary sinus aspergillosis is generally extended to the sinus antrum, base or thin orbital wall and ethmoid air cell region. We experienced a case of maxillary sinus aspergillosis which was extended directly to the soft tissue of the cheek. Methods: A 46-year-old man with acute myelogenous leukemia was consulted for the defect of the anterior wall of the maxillary sinus, and cheek. Radiologic and histologic findings were consistent with invasive maxillary sinus aspergillosis. The otolaryngology department performed debridement via endoscopic sinus surgery first. Coverage of the resulting defect in the anterior wall of the maxillary sinus and its inner layer was undergone by the plastic and reconstructive surgery department, using a pedicled superficial temporal fascia flap and a split thickness skin graft. The remaining skin defect of the cheek was covered with a local skin flap. Results: The patient went through an uneventful recovery. There was no recurrence during 6 months of follow-up. Conclusion: Maxillary sinus aspergillosis usually involves the orbit or the gingiva but in some cases it may directly invade soft tissues of the cheek. Such an atypical infection extending into the cheek may lead to a large soft tissue defect requiring coverage. Thus, any undiagnosed soft tissue defect involving the cheek or maxillofacial area, especially in immunocompromised patients, should be evaluated for aspergillosis. We present this rare case, with a review of the related literature.

• Journal of Chest Surgery
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• v.31 no.5
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• pp.549-551
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• 1998

Although dysphagia in patients with acute leukemia is usually related to reflux esophagitis, infectious esophagitis, chemotherapy1) and leukemic infiltration2), acute esophageal stricture resulting from chemotherapy in the patient with leukemia is very rare. A 40-year-old man with acute myelogenous leukemia was admitted for operation of esophageal stricture which was developed within 1 month of chemotherapy. An esophagectomy and esophagogastrostomy with pyloroplasty was carried out. Histology showed mucosal infiltration of mononuclear cells and transmural fibrosis involving submucosa and the muscle layer.

• Korean Journal of Clinical Laboratory Science
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• v.38 no.2
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• pp.82-86
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• 2006

Leukemia arises in hematopoietic progenitor cells and is characterized by impaired or blocked differentiation, uncontrolled proliferation and resistance to apoptosis. Molecular mechanisms underlying cellular functions by $As_2O_3$, however, have been poorly investigated. The consensus of several reports is that $As_2O_3$ induces apoptosis in leukemia cells by activating genes for apoptosis. The present study aimed to investigate the effects of $As_2O_3$ on the cell cycle and its morphological change and a relationship between the caspase-3 and $As_2O_3$-induced apoptosis. Caspase-3 is involved in $As_2O_3$-induced apoptosis in K562 cells. In this study, to address whether $As_2O_3$-induced apoptosis is mediated by caspase-3 activity, the same samples were probed with a specific antibody. The pretreatment of $25{\mu}M$ Z-VAD-fmk, a specific inhibitor of caspase, decreased $As_2O_3$-induced cytotoxicity. And $As_2O_3$ significantly increased the percentages of the cells accumulated in the G2/M phase of the cell cycle in a time- and dose-dependent manner. Chromatin condensational changes were observed with Hoechst 33258 staining after treatment of $As_2O_3$. It was shown that $As_2O_3$-induced apoptosis is controlled through caspase-3 activation. These results may provide a useful rationale for CML treatment.

• Journal of Cancer Prevention
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• v.23 no.4
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• pp.170-175
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• 2018

Background: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells. Methods: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated. Results: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5. Conclusions: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.

• The Korean Journal of Nuclear Medicine
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• v.36 no.5
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• pp.298-305
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• 2002

Purpose: Bone marrow scintigraphy has been used to evaluate the status of bone marrow in various hematologic disorders. We have analyzed the peripheral distribution pattern and central uptake ratio of bone marrow using anti-NCA-95 monoclonal antibody and the their correlation in patients with various hematologic malignancy. Materials and Methods: Bone marrow immunoscintigraphy was performed using Tc-99m anti-granulocyte monoclonal mouse antibody BW 250/183. Fifty patients were classified into four groups; 11 with acute myelogenous leukemia, 12 with acute lymphocytic leukemia, 15 with lymphoma and 12 with myelodysplastic syndrome. The extension of peripheral bone marrow was categorized into four grades: I, II, III and IV. The activity of central bene marrow was expressed as sacroiliac uptake ratio. Results: The patient's number was 4 in grade I, 27 in grade II, 15 in grade III and 4 in grade IV according to extension of peripheral bone marrow. The extension of peripheral bone marrow was marked (58% in grade III and IV) in myelodysplastic syndrome and acute lymphocytic leukemia and mild (93% in grade I and II) in lymphoma. Sacroiliac uptake ratio was highest ($8.5{\pm}4.0$) in myelodysplastic syndrome and lowest ($5.9{\pm}3.6$) in acute myelogenous leukemia, but not significantly different among four patient groups (p>0.05). Sacroiliac uptake ratio of whole patients was significantly different among four grades (p=0.003), but there was not correlated between grade of peripheral bone marrow and sacroiliac uptake ratio (r=0.05). Conclusion: The pattern of peripheral bone marrow extension and activity of central hemopoietic marrow were not specific to the disease entities. Response of hemopoietic bone marrow may be evaluated on both peripheral and central bone marrow in patients with hematologic malignancy.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.538-547
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• 2010

Purpose : This study aims to compare the outcome of total body irradiation (TBI)- or non-TBI-containing conditioning regimens for leukemia in children. Methods : We retrospectively evaluated 77 children conditioned with TBI (n=40) or non-TBI (n=37) regimens, transplanted at Chonnam National University Hospital between January 1996 and December 2007. The type of transplantation, disease status at the time of transplant, conditioning regimen, engraftment kinetics, development of graft-versus-host disease (GVHD), complications, cause of deaths, overall survival (OS), and event-free survival (EFS) were compared between the 2 groups. Results : Among 34 patients with acute lymphoblastic leukemia (ALL), 28 (82.4%) were in the TBI group, while 72.7% (24/33) of patients with myeloid leukemia were in the non-TBI group. Although the 5-year EFS of the 2 groups was similar for all patients (62% vs 63%), the TBI group showed a better 5-year EFS than the non-TBI group when only ALL patients were analyzed (65% vs 17%; $P$=0.005). In acute myelogenous leukemia patients, the non-TBI group had better survival tendency (73% vs 38%; $P$=0.089). The incidence of GVHD, engraftment, survival, cause of death, and late complications was not different between the 2 groups. Conclusion : The TBI and non-TBI groups showed comparable results, but the TBI group showed a significantly higher 5-year EFS than the non-TBI group in ALL patients. Further prospective, randomized controlled studies involving larger number of patients are needed to assess the late-onset complications and to compare the socioeconomic quality of life.

• Journal of Life Science
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• v.23 no.2
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• pp.197-206
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• 2013

The present study investigated whether leukemia-maintaining cells reside in a differentiation-resistant fraction using a megakaryocytic differentiation model of K562 cells. Treatment with phorbol-12-myristate-13-acetate (PMA) significantly inhibited the colony-forming efficiency of the K562 cells. At a PMA concentration of 1 nM or higher, colony was not formed, but approximately 40% of K562 cells still survived in soft agar. Approximately 70% of colony-forming cells that were isolated following the removal of PMA after exposure to the agent were differentiated after treatment with 10 nM PMA for 3 days. The differentiation rate of the colony-forming cells was gradually increased and reached about 90% 6 weeks after colony isolation, which was comparable to the level of a PMA-treated K562 control. Meanwhile, imatinib-resistant variants from the K562 cells, including K562/R1, K562/R2, and K562/R3 cells, did not show any colony-forming activity, and most imatinib-resistant variants were CD44 positive. After 4 months of culture in drug-free medium, the surface level of CD44 was decreased in comparison with primary imatinib-resistant variants, and a few colonies were formed from K562/R3 cells. In these cells, Bcr-Abl, which was lost in the imatinib-resistant variants, was re-expressed, and the original phenotypes of the K562 cells were partially recovered. These results suggest that leukemia-maintaining cells might reside in a differentiation-resistant population. Differentiation therapy to eliminate leukemia-maintaining cells could be a successful treatment for leukemia if the leukemia-maintaining cells were exposed to a differentiation inducer for a long time and at a high dose.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.54-61
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• 2005

Purpose: The granulocytic sarcoma which developed in leukemic patients are quite rare and it will have bad prognosis, but it's tumor pathogenesis and also their treatment are not yet established. Through this study we have tried to know their clinical course, prognosis and their end result of recent treatment. Material and Methods: Total 20 patients of granulocytic sarcoma which were developed in total 2,197 leukemic patients from April, 1998 to September, 2004 were treated at the leukemic center and the orthopaedic department of St. Mary's hospital, Catholic University of Korea, and followed them for 1~78 months(average 18 months). Results: Total 20 cases of granulocytic sarcoma was found in 14 cases of total 1,331 acute myelocytic leukemic patients(AML), 4 cases of total 744 of chronic myelocytic leukemic patients(CML), and only one case in total 122 of acute biphenotype of leukemia. And so their occurrence rate in leukmic patients are actually 0.91%, total 20 cases of granulocytic sarcoma in total 2,197 leukemic patients at same period. Their ages are average 28.3 years(4~52 years), and male are predominant(13 cases) than female(7 cases). Single involvement was found in 11 cases but multiple lesions are in 9 cases, and spine, brain, extremities, chest, and pelvic bone are involved in frequency. The granulocytic sarcoma was developed in various stages of the leukemia, ie, 8 cases in complete remission of leukemia, and 12 cases in the treatment process of AML. The pathohistologic evaluation of granulocytic sarcoma was done in 6 cases which was developed in their extremities, and confirmed numerous immature myeloblasts and lymphocytes mixed. The treatment of these granulocytic sarcoma was mainly limited for the treatment of leukemia by Glivac and massive steroid therapy(19cases) and also combined with the bone marrow transplantation(13 cases), but radiation therapy with average 3,500 rads in 15 cases out of total 20 sarcomas was also done, and followed them for average 17.5 months after development of granulocytic sarcomas. Finally their prognosis was so bad that 12 patients(60%) out of total 20 granulocytic sarcoma were dead in 6.5 months after sarcoma developed and we found the granulocytic sarcoma was more fatal if they are developed during the process of CML(mortality: 100%(4/4cases). Conclusion: The prognosis of granulocytic sarcomas in leukemic patients are quite fatal, and much more studies for their pathogenesis and ways of treatment should be performed continuously.

• Korean Journal of Veterinary Research
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• v.15 no.1
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• pp.27-38
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• 1975

The following tumors occurring naturally in the dog were studied pathologically and discussed briefly. Tumors of the skin and subcutis: Fibroma, Lipoma, Epidermal cyst, Melanosarcoma, Sweat gland adenoma, Mastocytoma (2 cases), Mastosarcoma, and Sebaceous gland carcinoma. Tumors of the spleen and lymph node: Fibrosarcoma of the capsule of spleen, Leiomysarcoma of the spleen, and Lymphosarcoma of the lymph node (2 cases). Tumors of the lung: Bronchogenic carcinoma (3 cases), Adenocarcinoma type, Squamous carcinoma type, and Undifferentiated (round cell) carcinoma type respectively. Tumors of the alimentary tract and liver: Fibroma of the stomach, Hemangioma of the liver, Bile duct carcinoma, Liver cell carcinoma, and Myelogenous leukemia manifested in the liver. Tumor of the peritoneum: Fibrosarcoma. Tumors of the urogenital system: Fibroma of the uterus, Fibroma of the prepuce, Follicular cyst of the ovary, Transmissible venereal tumor of the vagina (6 cases), Carcinoma of the kidney, Adenoma of the prostate (2 cases), and Seminoma of the testis. Tumors of the mammary gland: Mixed tumor (2 cases), and Myoepithelioma. Tumor of the nervous system: Neurofibrosarcoma of the thigh.