• Journal of the Korean Chemical Society
• /
• v.57 no.4
• /
• pp.439-446
• /
• 2013

Chitosan (CS) and hydroxypropylmethyl cellulose (HPMC) blend microspheres were prepared by water-in-oil emulsion technique and were loaded with an anti-cancer drug 5-fluorouracil (5-FU). CS-HPMC microspheres were characterized by Fourier transform infrared spectroscopy to confirm the cross-linking reaction. Scanning electron microscopy (SEM) was also used to assess the surface morphology of particles prepared. The quantity of release of 5-FU from the microspheres have been studied in terms of blend composition and amount of cross-linking agent. Differential scanning calorimetry and X-ray diffraction techniques indicated a uniform distribution of 5-FU particles in microspheres, whereas SEM suggested the spherical structure of the microspheres with slight rough surface. The in vitro drug release indicated that the particle size and release kinetics depend upon blend composition, amount of cross-linking agent used and amount of 5-FU present in the microspheres.

• Radiation Oncology Journal
• /
• v.30 no.3
• /
• pp.99-107
• /
• 2012

Purpose: The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. Materials and Methods: The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Results: Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Conclusion: Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

• Journal of Veterinary Clinics
• /
• v.35 no.4
• /
• pp.161-165
• /
• 2018

A 12-year-old gelding Warmblood Horse was presented with a corneolimbal mass in the right eye (OD) of 6 months duration. Clinical signs included ocular discomfort, persistent mucoid ocular discharge, and conjunctival hyperemia. The mass was excised by superficial keratectomy under sedation in a standing position, followed by a topical application of 0.04% mitomycin C (MMC), and a placement of a conjunctival advancement graft. The histopathological diagnosis was squamous cell carcinoma. One month after surgery, recurrence of the mass was suspected upon examination of the eye. Topical MMC and 5-fluorouracil followed by cryotherapy were applied as adjunctive therapies after debulking of the mass. The surgical site healed without complications and with a cosmetically acceptable result. No recurrence of the mass was noted four years following the second procedure.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.5
• /
• pp.2191-2194
• /
• 2014

Background: Fluorouracil-based regimens have been widely accepted and recommended in the guidelines for treating patients with early or advanced staged colon cancer, although results are controversial. Here we performed a systemic analysis to evaluate the impact of S-1 based regimens on response and survival of patients with colon cancer. Methods: Clinical studies evaluating the impact of S-1 based regimens on response and survival of patients with colon cancer were identified using a predefined search strategy. Summary response rates (RRs) to treatment were calculated. Results: Six clinical studies which including 227 patients with advanced colorectal cancer were considered eligible for inclusion. Two studies were conducted using combination of S-1 and Oxaliplatin, and four studies featured S-1 and irinotecan. Systemic analysis showed that, in all patients, pooled RRs was 43.17%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. No treatment related death occurred. Conclusion: This systemic analysis suggests that S-1 based regimens, both with oxaliplatin or irinotean are associated with acceptable response and toxicity in patients with colon cancer.

• Journal of Chest Surgery
• /
• v.29 no.5
• /
• pp.536-541
• /
• 1996

Between June 1988 and June 1994, twenty five patients with locAlly advanced esophageal carcinoma received preoperative chemotherapy (Cisplatln, 5-Fluorouracil with or without Etoposide) and followed by resection. All patients had clinical evidence of airway involvement or distant Iymphnode involve- ment (M 1 Iymphnode) on bronchoscopy or computed tomographic scans. The major response rate to chemotherapy decided by the postoperative stage was 48% (12125). The resection rate was 92% (23/25) with overall complete resection rate of 72% (18125). Two patients had exploratory laparotomy (thorn- cotomy) only. Thirteen patients had esophagogastrostomy with a combined abdominl and Rt. thoracic approach (Ivor Lewis operation), slx pAtients had transhiatal esophagectomy, four patients had esophagogastrostomy with a combined Rt. thoracotonly & abdominal, cervical approach. There were three postoperative deaths (12%). Follow-up duration was between 3.3 months to 65 months. Median survival ime of resected patients except hospital death was 14.8 months. Actuarial survival at 12, 24 months was 72.9%, 26.2%. Signifi- cant better survival was associated with responder group (postoperative stage less than lIB) (P=0.029). These results demonstrate that 1) Preoperative Cisplatin based combined chemotherapy Produce high response rate, 2) High complete resection rate with acceptable mortality rate occur after preoperative chemotherapy, 3) Better surviL dl can be anticipated if complete resection performed after major re- sponse to preoperative chemotherapy.

• YAKHAK HOEJI
• /
• v.55 no.1
• /
• pp.75-79
• /
• 2011

The replication competent adenoviral vector (AV), AdLPCDIRESE1A was generated and reported previously to have cytotoxic effects in some cell lines. In AdLPCDIRESE1A, the expression of cytosine deaminse (CD) and E1A genes are under the control of tumor-specific L-plastin promoter. CD enzyme can deaminate the nontoxic prodrug 5-fluorocytosine (5-FC) to the toxic 5-fluorouracil (5-FU). E1A gene is essential for viral replication. Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. Thus, we have conducted in vitro preclinical study to evaluate effectiveness of AdLPCDIRESE1A on HCC. The efficacy of cytotoxicity was measured by generation of cytopathic effect (CPE) and cell counting. We infected HepG2 cells with various MOI of vector alone or concurrent with 5-FC. Exposure of cells to AdLPCDIRESE1A generated a significant cytotoxic effect as compared to the control. Almost 83% of the cell had manifested the characteristic cytotoxic effect on day 9 after infection of cells with 10 MOI of vector. We also observed the additive cytotoxic effects when AdLPCDIRESE1A vector had been coadministrated with 5-FC. The results suggest that the use of AdLPCDIRESE1A/5FC may be value in treatment of liver cancer. Further animal studies are needed for clinical trial.

• Korean Journal of Microbiology
• /
• v.26 no.3
• /
• pp.207-214
• /
• 1988

A cytosine deaminase from the cell-free extract of an isolate was examined after ethyl alcohol reactionation. The enzyme catalyzed the conversion of 5-fluorocytosine to 5-fluorouracil by the possession of specificity to the substrate. The optimum temperature and storage time on the stability of the enzyme were at below $50^{\circ}C$ and near 2 days in tris-HCl buffer. The maximum activity was also presented ar 9.0 in pH and $45^{\circ}C$ in temperature. The pHs and temperatures for the enzyme activity ranged from 8.5-9.5 and from 40-$50^{\circ}C$, respectively. the presence of $Ag^{+}, Hg^{2+}, Zn^{2+}$ in the reaction mixture resulted in the marked inhibition in the activity, but 1mM of $Fe^{3+}, K^{+}$, or $Na^{+}$ increased the enzyme activity. The enzyme preparation was vot affected by inhibitors used except N-ethylmaleimide of 1 and 10mM, and considerably activated by 1mM of pyrophosphate and 10mM of phosphate.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.5
• /
• pp.255-259
• /
• 2003

Dendritic cells (DCs) play a critical role in various immune responses involving $CD4^+$ T cells and have been used to generate anti-tumor immunity. Chemotherapy induces severe side effects including immunosuppression in patients with cancer. Although immunosuppression has been studied, the effects of anticancer drugs on DCs are not fully determined. In this study, we demonstrated that CD40 activation strongly protected DCs from 5-fluorouracil (5-FU) or mitomycin C-induced apoptosis. DCspecific surface markers, including CD11c and major histocompatibility complex (MHC) class II, were used for identifying DCs. CD 40 activation with anti-CD40 mAb significantly enhanced the viability of DCs treated with 5-FU or mitomycin C, assayed by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). Fluorescence staining and analysis clearly confirmed the enhancing effect of anti-CD40 mAb on the viability of DCs, suggesting that CD40 activation may transduce critical signals for the viability of DCs. Annexin V staining assay showed that CD40 significantly protected DCs from 5-FU or mitomycin C-induced apoptosis. Taken together, this study shows that CD40 activation with anti-CD40 mAb has strong anti-apoptosis effect on DCs, suggesting that CD40 activation may overcome the immunosuppression, especially downregulation of number and function of DCs in chemotherapy-treated cancer patients.

• Archives of Pharmacal Research
• /
• v.27 no.6
• /
• pp.633-639
• /
• 2004

The expression of therapeutic transgenes in recombinant adenoviral vectors is a major cause of toxicity in dividing cancer cells as well as non dividing normal cells. To solve the problem of toxicity to normal cells, we have reported on a recombinant adenoviral vector system （AdLP-） in which the expression of the transgene is directed by the tumor-specific L-plastin promoter （LP） （Chung et al., 1999）. The object of this study was to generate a recombinant adenoviral vector system which would generate tumor cell specific expression of cytosine deaminase （CD） gene. We report the construction of a replication-incompetent adenoviral vector in which CD is driven by the L-plastin promoter （AdLPCD）. Infection of 293 cells by AdLPCD generated the functional CD protein as measured by HPLC analysis for the conversion of 5-Fluorocy-tosine （5-FC） to 5-Fluorouracil （5-FU）. HPLC analysis in conjunction with counting radioactivity for ［6-$^3$H］-5FC and ［6-$^3$H］-5FU demonstrated vector dose-dependent conversion of 5-FC to 5-FU in AdLPCD infected ovarian cancer cells. The results from present and previous studies（Peng et al., 2001； Akbulut et al., 2003） suggest that the use of the AdLPCD／5-FC system may be of value in the treatment of cancer including microscopic ovarian cancer in the peritoneal cavity.

• Korean Journal of Microbiology
• /
• v.26 no.4
• /
• pp.368-374
• /
• 1988

Enzymological proprties of an extracellular cytosine deaminase from Bacellus polymyxa YL 38-3 were investigated. The extracellular enzyme was very stable, and optimum pH and temperature for the enzyme activity were found to be near pH 6.0 in 0.2M potassium phosphate buffer and at $30^{\circ}C$, respectively. 5-Fluorocytosine was converyed to 5-fluorouracil by the enzyme, but 5-methylcytosine was not to thymine by it. The enzyme activity was completely inhibited by some heavy metal ion such as 1mM of $Cd^{2-}$ and $Hg^{2+}$, and by 1mM of p-chloromercuribenzoate, respectively. The enzyme activity was inactivated about 75% by 1mM of o-phenanthroline and monoiodoacetate. But the enzyme activity was stimulated up to 200% by 1mM of 2-mercaptoethanol.