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Colorectal cancer appears to have rapidly increased over the past two decades in Korea. Environmental factors, characterized by a western life style, seem to be closely related to the increased risk of colorectal cancer. Higher intakes of meat, a lower vegetable intake, a lack of physical activity, obesity, and alcohol drinking have been suggested to be risk factors for colorectal cancer in the numerous epidemiologic studies. Several specific associations have also been observed between genetic polymorphisms and colorectal cancer. Moreover, it has been postulated that environmental factors and a genetic predisposition work in concert in colorectal cancer development. A stronger association between red meat intake and colorectal cancer among those with rapid acetylators at either the NAT1 or NAT2 locus was reported, particularly for colorectal cancer associated with K-ras mutations. The protective effect of the homozygous variant TT form of the MTHFR genotype on the risk of colon cancer seems to be modified by the level of methyl diets, i.e., by folate, which has a protective effect, or conversely by alcohol. The insulin-related pathway, which possibly explains at a mechanistic level the effect of physical activity and obesity on colon cancer, appears to be a common denominator in colon cancer and in other metabolic disorders, such as diabetes mellitus and dyslipidemia. Hyperinsulinemia has been proposed as an explanation for the association between a Western lifestyle and colon cancer risk. Further studies, that incorporate both genetic and environmental factors, are needed to fully explain and identify the underlying pathway of colorectal carcinogenesis.
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To estimate the number of cancer cases during 2002 in Korea through a nationwide hospital based cancer registration by the Korea Central Cancer Registry (KCCR).
One hundred and thirty nine hospitals participated in the KCCR program in 2002. Cancer cases were coded and classified according to the International Classification of Diseases for Oncology 2nd edition (ICD-O-2). The software program "IARC Check" was used to evaluate the quality of registered cancer cases. Of the 122,770 malignancies registered, 11,732 (9.6%) duplicated malignancies were excluded. Among the remaining 102,677 malignancies, 3,652 (3.6%) cases with carcinoma in situ (Morphology code/2) were separated. Finally, 99,025 malignancies were analyzed.
Of the total of 99,025 malignancies, 55,398 (55.9%) cases were males and 43,627 (44.1%) were females. More than one third of cases were from the elderly (65 years old and more). The six leading primary cancer sites in the order of their relative frequency, were stomach (24.0%), followed by the lung (16.0%), the liver (15.4%), the colorectum (11.6%), the bladder (3.2%), and the prostate (3.0%) among males. In females, the breast (16.8%) was the common cancer site, followed by the stomach (15.3%), the colorectum (10.7%), the thyroid gland (9.5%), the cervix uteri (9.1%), and the lung (6.6%).
With the continued increase in cancer cases especially prostate cancer among males and thyroid cancer among females, the total number of registered cancer cases in Korea continues to rapidly increase.
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To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX 4), as a first-line therapy for patients with metastatic colorectal cancer.
Between March 2001 and August 2003, fifty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m2 as a 2-hour infusion at days 1 plus LV 20 mg/m2 over 10 minutes, followed by 5-FU bolusa 400 mg/m2 bolus and 22 hour continuous infusion of 600 mg/m2 5-FU at day 1~2. This treatment was repeated in 2 week intervals.
The objective response rate was 40% on an intent-to-treatment analysis. Three patients (6%) demonstrated a complete response and nineteen patients (38%) showeda partial response. Sixteen patients (32%) showed a stable disease and eleven patients (22%) progressed during the course of the treatment. The median time to progression and overall survival time wereas 6.6 months (95% CI: 4.98~8.02 months) and the median overall survival time was 17.0 months (95% CI: 9.15~24.85 months) from the start of the chemotherapy, respectively. A total of 275 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1~2 anemia (23.5%), neutropenia (25.3%) and thrombocytopenia (10.6%). There were only 2 cycles of neutropenic fever. The most common non-hematologic toxicities were grade 1~2 nausea/vomiting (10.9%), diarrhea (9.1%) and grade 1 neuropathy (18.0%). There was no treatment related death.
The modified folfox 4 regimen is safe and effective regimen as a first-line therapy in advanced colorectal cancer patients.
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The combination of chemoradiation and fluorouracil based chemotherapy has been the standard adjuvant treatment for colorectal cancer patients. The aim of this study was to evaluate treatment outcome of patients classified by the new AJCC staging system and to compare treatment outcome of oral doxifluridine and the standard Mayo Clinic regimen after chemoradiation in advanced rectal cancer patients.
One hundred nine patients underwent curative surgical resection and chemoradiation followed by chemotherapy. 45 Gy pelvic irradiation was given to the entire pelvis and the boost radiation with 50.4 to 54 Gy, and simultaneously 5-fluorouracil (5-FU) 375 mg/m2/day was given on day 1~3 and 26~28. After the completion of chemoradiation, patients were given either 6 cycles of the Mayo Clinic regimen (5-FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous bolus infusion on day 1~5, every 4 weeks) or oral doxifluridine (600 mg/m2/day) for 1 year.
The median follow-up duration was 30 months. Among 102 evaluable patients, 38 patients (37.3%) relapsed: the locoregional recurrence in 10 patients (9.8%) and systemic relapse in 28 patients (27.5%). The systemic relapse rate was 15.6% in the stage IIA, 25.0% in the stage IIIB , and 59.1% in the stage IIIC (p=0.048). The 5-year disease-free survival (DFS) rate was significantly higher in the IIA and IIIA patients than the IIIB and IIIC patients (72% and 100% vs 48.1% and 11.2%, respectively. p<0.001). The 5-year overall survival (OS) rate was also significantly different between in the IIA/IIIA patients and the IIIB/IIIC (67.3%/100% vs 48.4%/22.3%. p<0.001). However, the difference in DFS or OS between the oral doxifluridine group and the Mayo Clinic regimen group was not significant. Cox regression multivariate analyses showed that the new AJCC stage and tumor differentiation were significant independent prognostic factors in DFS and OS.
These results support that the new AJCC staging system is superior to Dukes' staging system in the prognostic stratification. Regarding DFS and OS, oral doxifluridine is comparable to the standard Mayo Clinic regimen in rectal cancer patients when combined with postoperative chemoradiation. Stage IIIC patients should be selected for aggressive therapy as they have a dismal prognosis.
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The purpose of this study was to assess the efficacy and safety of radiofrequency ablation (RFA) to treat hepatic metastasis in patients with colorectal carcinoma.
Between May 1999 and July 2002, a total of 45 tumors in 24 patients with colorectal cancer were treated with RFA. Thirteen patients received systemic chemotherapy after the RFA procedure. The ablation was performed percutaneously under ultrasound guidance using cool-tip or expandable electrodes and an RF generator. The medical records as well as the CT scan results taken every 3 months were retrospectively reviewed.
The median follow-up duration of the surviving patients was 11.7 months (4.6~32.2 months). Complete tumor necrosis was achieved in 17 patients (70.8%) on an immediate (<24 hrs) CT scan. The median survival was 17.1 months. The 1- and 2-year survival rates were 80.5 and 25.8%, respectively. In a univariate analysis, complete necrosis, tumor size and post-RFA chemotherapy were significant factors for survival. Nineteen of the 24 patients developed a recurrence or progressed (79.2%). The median progression free survival was 5.5 months. There were no treatment related deaths or serious adverse effects, with the exception of one case of respiratory failure.
These results suggest that RFA is a well-tolerated and effective method to treat hepatic metastasis in colorectal carcinomas.
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This study was conducted to explore whether CDCA derivatives induce apoptosis in a stomach cancer cell line, and to dissect the detailed mechanism underlying apoptosis.
The human stomach cancer cell line, SNU-1, cells were treated with the synthetic CDCA derivatives, HS-1199 and HS-1200. DNA and mitochondrial stains were used to detect apoptotic cells by fluorescence imaging or flow cytometry. The caspase-3 activity was measured by Western blotting.
Both the HS-1199 and HS-1200 induced decreased viabilities of the SNU-1 cells, in time-dependent manners. The CDCA derivatives demonstrated various apoptosis hallmarks, such as mitochondrial changes (reduction of MMP, cytochrome c release, and Smac/ DIABLO translocation), activation of caspase-3 (resulting in the degradation of PARP and DFF45), DNA fragmentation and nuclear condensation.
The CDCA derivatives, HS-1199 and HS-1200, both induced apoptosis of the SNU-1 gastric cancer cells in caspase- and mitochondria-dependent fashions. Many important issues relating to their therapeutic applications remain to be elucidated.
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The combination of cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) administration, as adjuvant chemotherapy after curative resection for gastirc cancer, was compared with 5-fluorouracil (5-FU) administration alone. This paper reports the results of a prospective randomized comparison of the two regimens, PELF and 5-FU.
From August 1996 to July 1999, 54 patients were selected subsequent to being diagnosed with stage III cancer after a curative resection for gastric cancer. The patients were stratified according to stage IIIA/IIIB and subtotal/total gastrectomy, and then they were randomized into each treatment group, i.e. the PELF or 5-FU alone groups.
54 assessable patients were enrolled in this study: 28 received PELF and 26 received 5-FU alone. 12 patients relapsed in each group and the median follow-up duration was 42 months (range: 10~77 months). The overall survival rate and disease-free survival rate (DFS) were not significantly different between two groups, (5-year survival of PELF vs. 5-FU: 57% vs. 64%, 5-year DFS: 54% vs. 51%). The PELF combination was more toxic in terms of anemia, anorexia, nausea and diarrhea than the 5-FU.
This study showed that the PELF combination, as an adjuvant therapy for gastric cancer after a curative resection, was a less effective treatment, and it had more toxic effects than the 5-FU.
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c-myc, bcl-2 and p53 are known to regulate apoptosis. There has been growing interest in analyzing their contribution to the pathogenesis and prognosis in a variety of human cancers. This study was undertaken to investigate the expression of these proteins in pulmonary adenocarcinomas and to determine their relationship with clinicopathologic parameters and survival.
Archival tumor tissues from 61 patients with adenocarcinoma of lung were analyzed by immunohistochemistry for the expression of c-myc, bcl-2 and p53 proteins. Clinical information was obtained through the computerized retrospect database from the tumor registry.
Of 61 patients, 32 were men and 29 women with the median age 63 years. 4 had stage I disease, 2 had stage II disease and 55 had stage III disease. The expression of c-myc protein was identified in 13% (8/61) tumors, bcl-2 protein was detected in 1.6% tumors (1/61) and p53 was detected in 77% (47/71) tumors. The association of the expression of c-myc, bcl-2 and p53 was not detected. The survival time was longer in patients expressing c-myc protein than in patients without the c-myc protein expression (p=.045). Neither bcl-2 nor p53 showed the correlation to clinicopathologic variables.
Our data suggest the involvement of p53 alteration in the pathogenesis of lung adenocarcinoma. The c-myc expression in some tumors indicates that c-myc alone may not contribute critically to the development and/or the progression of these tumors. It, however, correlated to the survival time, suggesting the c-myc expression as a favorable prognostic factor possibly through the apoptosis pathway.
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The shuttle vector pGP50 is capable of replicating in
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Isolated diaphragmatic metastasis arising from colorectal cancer has been reported only one case in the literature presently. Here, we presented a new case and discussed the possible pathogenesis and the treatment options. A 42-year-old male patient had received anterior resection for sigmoid colon cancer. Although the increased serum CEA level was detected 20 months after the surgery, metastatic lesion could not be detected by repeated colonoscopy, CT scan, bone scan or PET scan for 35 months. We could detect a suspicious metastatic lesion on the liver by CT scan at 56 month after the surgery. During a second-look operation, we found a solitary metastasis on the diaphragm and removed it along with the 1 cm tumor-free resection margin. Although the prognosis associated with skeletal metastasis is poor, the complete resection of isolated diaphragmatic metastasis and subsequent appropriate adjuvant chemotherapy may achieve a cure the disease provided that other metastatic lesions are absent.
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