• Journal of Gastric Cancer
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• v.1 no.4
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• pp.197-201
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• 2001

Purpose: There are variants of gastric cancer assoclated with predominantly peritoneal spread of with haematogenous metastases. Perioperative intraperitoneal chemotherapy as an adjuvant to surgery is considered as a rational therapeutic modality to prevent peritoneal spread. We evaluated the influence of early postoperative intraperitoneal chemotherapy on the prognosis of resectable advanced gastric cancer. Materials and Methods: From 1990 to 1995, 246 patients with biopsy proven advanced gastric cancer were enrolled in the study. Among them 123 patients received early postoperative intraperitoneal mitomycin C and 5-fluorouracil. The survival rate was calculated using by the Kaplan-Meier method and was compared using the log-rank test according to 13 clinico-pathologic factors. Multivariate analysis was performed with the Coxproportional hazards model. Results: Gastric resection plusearly postoperative intraperitoneal chemotherapy showed an improved survival rate as compared to surgery alone ($54.1\%\;versus\;40.3\%;$ P=0.0325). Depth of tumor invasion, degree of regional lymph vode metastasis, distant metastasis, tumor size, tumor location, extent of gastric resection, and curability of surgery significantly influenced survival. When a multivariate analysis was performed, depth of tumor invasion, lymph node metastasis, early postoperative intraperitoneal chemotherapy, curability of surgery, and extent of gastric resection emerged as the statistically significant and independent prognostic factors. Conlusion: Early postoperative intraperitoneal chemotherapy is one of the independent prognostic indicators of resectable advanced gastric cancer.

• Tuberculosis and Respiratory Diseases
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• v.77 no.6
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• pp.262-265
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• 2014

The combination chemotherapy of irinotecan with 5-fluorouracil and leucovorin (FOLFIRI regimen) was recently proven to be beneficial in patients with advanced colorectal cancer. Pulmonary toxicity is very rare in adverse effects of irinotecan. No case of organizing pneumonia (also known as bronchiolitis obliterans organizing pneumonia) associated with FOLFIRI chemotherapy has been reported. We experienced a case of a 62-year-old man who presented persistent dry cough and progressive dyspnea after receiving chemotherapy with FOLFIRI regimen. After surgical lung biopsy, the patient was diagnosed with FOLFIRI chemotherapy-induced organizing pneumonia which was successfully treated with steroid therapy.

• Tuberculosis and Respiratory Diseases
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• v.75 no.3
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• pp.111-115
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• 2013

Although the relationship between malignancy risk with systemic sclerosis (SSc) has been inconclusive, there are some previous studies for a positive correlation. Most patients with SSc have some degree of lung parenchymal involvement in the form of interstitial thickening and fibrosis. Interstitial lung disease is the most common pulmonary manifestation of SSc. Interstitial lung disease following chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX]) is an uncommon life-threatening complication and it is induced by oxaliplatin. We report a case of multiple cancers in a patient with SSc and aggravated interstitial lung disease by chemotherapy.

• Biotechnology and Bioprocess Engineering:BBE
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• v.10 no.3
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• pp.180-185
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• 2005

Cytosine deaminase (cytosine aminohydrolase, EC 3.5.4.1) stoichiometrically catalyzes the hydrolytic deamination of cytosine and 5-fluorocytosine to uracil and 5-fluorouracil, respectively. Amino acid residues located in or near the active sites of the intracellular cytosine deaminase from chromobacterium violaceum YK 391 were identified by chemical modification studies. The enzymic activity was completely inhibited by chemical modifiers, such as 1mM NBS, chloramine-T, $\rho-CMB,\;\rho-HMB$ and iodine, and was strongly inhibited by 1mM PMSF and pyridoxal 5'-phosphate. This chemical deactivation of the enzymic activity was reversed by a high concentration of cytosine. Furthermore, the deactivation of the enzymic activity by $\rho-CMB$ was also reversed by 1mM cysteine-HCI, DTT and 2-mercaptoethanol. These results suggested that cysteine, tryptophan and methionine residues might be located in or near the active sites of the enzyme, while serine and lysine were indirectly involved in the enzymic activity. The intracellular cytosine deaminase from C violaceum YK 391 was assumed to be a thiol enzyme.

• BMB Reports
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• v.30 no.3
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• pp.167-172
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• 1997

The yeast Saccharomyces cerevisiae, mutant CH117, shows a drug-hypersensitivity (dhs) to cycloheximide, bleomycin, actinomycin D, 5-fluorouracil. nystatin, nigericin and several other antibiotics. CH 117 was also temperature-sensitive (ts). being unable to grow at $37^{\circ}C$ and secreted more invertase and acid phosphatase into the medium than the parent yeast. CH117 grows very slowly and the cell shape is somewhat larger and more sensitive to zymolyase than the wild type cells. Light microscopic and electron microscopic observation also revealed abnormality of the mutant cell wall. These characteristics indicate that CH117 has a defect in an essential component of the cell surface and that the cell wall which performs barrier functions has become leaky in the mutant. We screened a genomic library of wild type yeast for clones that can complement the mutation of CH117. A plasmid, pCHX1, with an insert of 3.6 kilobases (kbs) could complement the dhs and ts of CH117. Deletion and subcloning of the 3.6 kb insert showed that a gene for the complementation of mutant phenotypes was located in 1.9 kbs Puvll-Hindlll fragment.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.143-149
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• 2005

We have demonstrated previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase (CD) gene is driven by the tumor-specific L-plastin promoter. The object of this study was to evaluate the efficacy of AdLPCD together with 5-fluorocytosine (5-FC) in suppression of the growth of established human tumor cells of ovary, Consistent with the knowledge that infection of OVCAR-3 cells with AdLPCD resulted in expression of a functional intracellular CD enzyme capable of converting 5-FC to 5-fluorouracil (5-FU) (Chung and Deisseroth, 2004), statistically significant differences in cytotoxicity were observed when AdLPCD infected cells were also exposed to 5-FC for 6 days (p=0.05), 9 days (p<0.0005) and 12 days (p<0.005), compared to 5-FC exposure alone, These results indicate that the CD gene delivered by adenoviral vector could efficiently sensitize OVCAR-3, otherwise non-toxic 5-FC. On the other hand, SKOV-3 cells, an ovarian carcinoma cell line, were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The results of present study suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.200-200
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• 1994

Thioglycerol과 g1ycerol로부터 rac-1-S-octa-decyl-2-O-palmitoyl-1-S-thioglycerol-3-phosphate (DL -PTBA-P)와 rac -1-O-octadecyl -2-O-palmitoyl-g1ycerol-3-phosphate (DL-PBA-P)등을 합성하였고, 이들에 ara-C유도체인 ara-CMP morpholidate를 반응시켜 최종 산물인 ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara-CDP-DL-PTCA 및 ara-CDP-DL-PTBA등을 합성하였다. 이들 최종 산물의 항암효과는 L1210 lymphoid leukemia, P388 leukemia등의 암세포주를 사용하여 실험하였다. 암세포인 L1210, P388 leukemia 세포의 성장에 대한ara-CDP-DL-PTBA의 시험관 내 세포성장 억제정도를 알아보기 위하여 비색법인 MTT방법을 시행하였으며, 검체의 세포성장 억제능을 비교하기 위하여 대조군으로 5-Fluorouracil (5-FU)을 사용하였다.

• Journal of Korean Neurosurgical Society
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• v.44 no.4
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• pp.273-276
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• 2008

Although adenoid cystic carcinoma (ACC) of the lacrimal gland is a rarely encountered orbital tumor, it invades intracranially more frequently than carcinomas of other glands in the head and neck. A 52-year-old man underwent orbital exenteration and resection of intracranially extended tumor via a fronto-orbito-zygomatic approach in combination with a transfacial approach. Histopathologically, the tumor showed perineural, vascular, and lymphatic invasion. Additionally, he received radiotherapy (60 Gy) and adjuvant systemic cisplatin and 5-fluorouracil chemotherapy due to residual tumor in the orbit and systemic metastases (lung, ribs, and spines). He was free of progression and recurrence at 6 months after treatment. The authors report a case of skull base invasion by an ACC of the lacrimal gland to remind neurosurgeons planning intervention that this disease shows a tendency to invade intracranially.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.80-80
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• 1997

The object of this study was to develop a gene therapy strategy for ovarian cancer. We have previously shown that AV with a L-plastin (LP) promoter infects breast and ovarian cancer cells and expressed ${\beta}$-galactosidase cDNA in preference to normal fibroblast cells and hematopoietic cells. We now report on the cytotoxicity of Ad.LP.CD, an AV carrying a CD cDNA which converts the pro-drug, 5-Fluorocytosine (5-FC) into the toxic drug 5-Fluorouracil (5-FU). Infection of Ad.LP.CD into either 293 cells or ovarian cancer cells generated the functional CD as measured by HPLC analysis. Using a ratio of AV to OVCAR3 cell of 100 and a 5-FC concentration of 100 ${\mu}$M, we achieve an over 95 % of cell growth inhibition. We are using flow cytometry analysis for ${\beta}$ -galactosidase and ovarian cancer associated folate receptor to screen primary ascites samples for infectivity after infection with an adenoviral vector, i.e., Ad.LP.LacZ. This vector system may be of value in the treatment of microscopic disease of ovarian cancer in the peritoneal cavity.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.393-399
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• 2004

For the efficient determination of activity against solid tumors, an in vitro tumor model that resembles the condition of in vivo solid tumors, is required. The purpose of this study was to establish a rapid culture method and viability assay for an in vitro 3-dimensional tumor model, multicellular spheroid (MCS). Among 12 human cancer cell lines, a few cell lines including DLD-1 (human colorectal carcinoma cells) formed fully compact MCS which was adequate for in vitro viability assay. DLD-1 MCS showed steady growth reaching $700\;{\mu}m$ diameter after 11 day culture. DLD-1 cells grown as MCS showed significant increase in $G_0/G_1$ phase compared to the monolayer cells (73.9% vs 45.7%), but necrotic regions or apoptotic cells were not observed. The cells cultured as MCS showed resistance to 5-FU (10.3 fold higher $IC_{50}$) compared to monolayers, however, tirapazamine (a hypotoxin) showed similar activity in both culture systems. In summary, MCS may be a valid in vitro model for activity screening of anticancer agents against human solid tumors and also exploitable for studying molecular markers of drug resistance in human solid tumors.