Cancer Research and Treatment

Cermline Mutation of RET Gene in A Multiple Endocrine Neoplasia Type 2A ( MEN2A ) Family: Hee Young Yang, Young Jin Park, Hyuk Joon Kwon, Kuk Jin Choe; J Korean Cancer Assoc. 1999;31(5):867-875.

Abstract PDF: PURPOSE
Multiple Endocrine Neoplasia Type 2A (MEN 2A) is an autosomal dominant disease characterized by development of the medullary thyroid cancer, adrenal pheochromocytoma and parathyroid hyperplasia. Gennline mutations of RET gene, which cause a susceptibility to MEN 2A syndrome, have been reported in MEN 2A families. The identification of germline mutation in family members with hereditary tumor syndrome makes the presymptomatic diagnosis possible. However, there are only a few reports on the germline mutation of RET gene in Korean patients with MEN 2A. This study was performed to investigate the germline mutation of RET gene in a Korean MEN 2A family.
MATERIALS AND METHODS
Blood samples were taken from family members of a MEN 2A family. Mutational status was investigated using single strand conformation polymorphism (SSCP) method, and following direct sequencing. Basal level of calcitonin was measured, and calcium provocation test was done when the result of basal level of calcitonin was equivocal.
RESULTS
A missense type germline mutation of RET gene was identified at codon 634 (TGC->TGG) in eight patients from the family. All patients with the germline mutation of RET gene showed elevation of calcitonin level either in basal test or in calcitonin provocation test.
CONCLUSION
We identified a germline mutation of RET gene in a family with MEN 2A, and it would make the accurate presymptomatic diagnosis possible.

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p53 Mutation and Functional Analyses by Using Yeast Functional Assay: Byung Joo Song, Chin Seung Kim, Il Soo Kim, Su Mi Han, Hae Jung Nam, Mi Uk Chin, Dong Hwan Kim, Dong Hwang Kim, Hyun Pil Cho, Young Ho Moon; J Korean Cancer Assoc. 1999;31(5):876-886.

Abstract PDF: PURPOSE
Mutation of the p53 tumor suppressor gene is the most common genetic defect in all human tumors. Because of the widespread mutations and polymorphism in the p53 gene, the conventional screening methods cannot distinguish between polymorphisms or functionally silent mutations and inactivating mutations. It is well known that plasmids can be generated by homologous recombination in vivo in the yeast by cotransforming the PCR product with a linearized yeast expression vector encoding part of a gene and a selectable marker gene. The aim of this study is to develop more easy and reliable method for functional assay of p53 mutation.
MATERIALS AND METHODS
We constructed a gap vector which can reliably and conveniently be used to screen p53 mutations in a simple yeast growth assay. The gap vector was constructed as follows: About 100 bp DNA fragments containing parts of N- and C- terminal portion of p53 were cloned into XbaI/SmaI and HindIII/XhoI sites of yeast expressing vector, respectively. The gap vector was obtained by double cutting with SmaI and HindIII followed by gel elution. Yeast was transformed with the reporter vector containing three tandem copies of the consensus p53 binding site by lithium acetate-mediated method. RT-PCR amplification of p53 transcripts from cell lines or tumor tissues was carried out. To investigate whether p53 gene is mutated or not, yeast containing reporter gene was cotransformed with PCR product and linearized gap vector, plated on SD medium minus histidine, and incubated for 3 days. The colonies on selective media were isolated and characterized.
RESULTS
The tumor tissues examined were one hepatocellular carcinoma, three breast cancers, two stomach cancers and two colon cancers. One hepatocellular carcinoma tissue had mutation in both alleles of the p53 gene, and 7 cancer tissues had heterozygous mutations in the p53 gene. The result of functional assay was well correlated with mutational analysis by sequencing.
CONCLUSION
p53 functional assay system might be easy and reliable method for functional screening of p53 on tumor tissues and this might be used for screening of other mutated gene. This technique, FASAY, requires only a few steps, can be automated readily and should permit screening for germline or somatic heterozygous mutations in any gene whose function can be monitored in yeast.

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Genetic Alterations of p16Ink4A and p15Ink4B in Gastric Carcinomas: Kwon Hur, Han Kwang Yang, Ja June Jang, Jin Pok Kim, Dae Young Kim; J Korean Cancer Assoc. 1999;31(5):887-897.

Abstract PDF: PURPOSE
p16Ink4A and p15lnk4B, encoded by the genes located on chromosome 9p21, are cyclin-dependent kinase 4 inhibitors and are the upstream regulators of pRB (retinoblastoma protein) function and are involved in the regulation of cell cycle in mammalian cells. It has been demonstrated that p16 and p15 genes are frequently deleted, mutated, and hypermethylated in many malignancies and cancer cell lines. This study was performed to investigate the genetic alteration and immunohistochemical profile of p16 and p15 in gastric carcinomas.
MATERIALS AND METHODS
We examined 30 primary gastric cancer samples using PCR- SSCP (Polymerase chain reaction-single strand conformation polymorphism), DNA sequencing, PCR-based hypermethylation assay, and immunohistochemistry.
RESULTS
No homozygous deletion was detected in either pl6 or p15 gene, and only one gastric carcinoma sample showed mutation of p16 gene and p15 gene. However, hyper-methylation of 5' CpG islands was observed in 53.6% of exon1 of p16 gene and in 46.4% of exon 1 of pl5 gene. By immunohistochemistry of p16, nuclear under-expression was observed in 58.6%, whereas nuclear over-expression was detected in 31% of formalin-fixed, paraffin-embedded gastric cancer tissues.
CONCLUSIONS
Our results suggest that the p16 and p15 tumor suppressor genes may play an important role in gastric carcinogenesis and may be inactivated not by deletions or mutations but mainly by hypermethylation of their 5' CpG islands. There was a good correlation between methylation study and immunohistochemical results in p16 genes.

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Type of Intestinal Metaplasia in the Surrounding Mucosa of Gastric Carcinoma and Expression of bcl-2, p53 and c-erbB-2 Prtein in Gastric Carcinoma: Seung Che Cho, Kun Young Kwon; J Korean Cancer Assoc. 1999;31(5):898-911.

Abstract PDF: PURPOSE
This study was carried out to clarify significance of types of intestinal metaplasia and roles of bcl-2, p53 and c-erbB-2 protein in the development of gastric carcinoma.
MATERIALS AND METHODS
Total one hundred fifty nine cases of surgically resected stomachs with benign ulcer (n=21), dysplasia (n=18) and gastric carcinoma (n=120) were studied histologically, histochemically and immunohistochemically.
RESULTS
Type III intestinal metaplasia was significantly more common in the carcinoma patients in older age group. Bcl-2 expression was found in 94.4% cases of dysplasia and 75.0% cases of carcinoma. Positivity for bcl-2 protein was significantly higher in intestinal type carcinomas than in diffuse type carcinomas (p=0.000). The expression of p53 protein showed 50.0% cases of dysplasia and 49.2% cases of carcinoma. The expression of p53 protein was significantly correlated with depth of invasion (p=0.000), regional lymph node metastasis (p=0.001), and tumor size (p=0.001). C-erbB-2 protein was only expressed in 15.0% cases of carcinoma. The expression of c-erbB-2 protein was found more often in advanced carcinomas (p=0.001) and carcinomas with regional lymph node metastasis (p=0.003).
CONCLUSION
Type III intestinal metaplasia was associated with age, but not with types of gastric carcinoma. Bcl-2 protein is probably involved in dysplastic lesion of gastric carcinogenic sequence and associated with intestinal type carcinoma, and p53 protein is also involved in dysplasia. p53 protein and c-erbB-2 protein may have a role of tumor invasion and nodal metastasis as poor prognostic factors.

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Matrix Metalloproteinases and Their Inhibitors in Gastric Carcinoma: Byung Sik Kim, Yutaka Yonemura, Hideto Fujita, Naomi Nojima, Taiichi Kawamuta, Sachio Fushida, Takashi Fujimura, Itsuo Miyazaki, Kouichi Miwa, Hiroshi Itoh, Raul Falla, Yoshio Endo, Takuma Saski, Hiroshi Yamamoto; J Korean Cancer Assoc. 1999;31(5):912-920.

Abstract PDF: No abstract available.

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The Clinical Value of CD44 in Gastric Cancer: Kyung Ho Ryu, Hyung Chul Kim, Moo Jun Baek, Ok Pyung Song, Chang Jin Kim; J Korean Cancer Assoc. 1999;31(5):921-930.

Abstract PDF: PURPOSE
This research was performed to investigate the relationship between CD44 and cancer cell invasion depth, histologic differentiation, tumor size and lymph node metastasis in the gastric carcinoma.
MATERIALS AND METHODS
In 20 cases of early gastric cancer and 40 cases of advanced gastric cancer, the immunohistochemical staining for CD44v3 and CD44v5 was performed.
RESULTS
1. In all 60 cases, the positive rates for CD44v3 and CD44v5 were 18.3% and 71.7% respectively. 2. CD44v5 was expressed in 45% of early gastric cancer and 85% of advanced gastric cancer. 3. Larger tumor exhibited higher positive rates for CD44v5. 4. There were 28 cases of lymph node metastases out of 43 cases of CD44v5-positive primary gastric carcinoma (65.1%), and were 4 cases of lymph node metastases out of 17 CD44v5-negative cases (23.5%). 5. The 5 year survival rate was low in CD44v5- positive cases (p-value=0.039).
CONCLUSION
The tumors that exhibit deep invasion and have large size and lymph node metastases tend to have more frequent expression of CD44v3 and CD44v5. In especially CD44v5. We found a good correlation between he expression of CD44v5 and the established prognostic factors. Actually we can use the CD44v5 rather than CD44v3 as a prognostic factor in advanced gastric cancer.

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In Vitro Chemosensitivity Test for the Evaluation of Efficiency of Hyperthermia in Gastrointestinal Cancer Cell Lines: Jeong Hwan Yook, Byeong Yul Ahn, Geum Hee Koo, Hun Seo, Choon Sik Jeong, Sung Tae Oh, Byung Sik Kim, Kun Chun Park, Jin Cheon Kim; J Korean Cancer Assoc. 1999;31(5):931-938.

Abstract PDF: PURPOSE
This study was designed to establish the experimental background of intra- peritoneal hyperthermo-chemotherapy in gastrointestinal cancer.
MATERIALS AND METHODS
We established stomach cancer cell lines; KATO-III, MKN45, AMC1 and colon cancer cell lines; AMC5, AMC6, CloneA, CCL188, C106, KM-12C. We performed chemosensitivity test by using MTT assay and calculated ICso of each chemotherapeutic agent. We confirmed antitumor effect of hyperthermia at 40C and 43C and antitumor synergistic effect with each chemotherapeutic agent at 40C and 43C.
RESULTS
The ICso was calculated in 7 (78%) of 9 cell lines for 5-FU, 6 (67%) for MMC, 5 (56%) for ADM, 1 (11%) for CDDP and VP-16. Antitumor effect of hyperthermia at 40C was not found, but, that at 43C was found except KATO-III and AMC6. In stomach cancer cell lines, antitumor synergistic effect of hyperthermia with anticancer drugs at 43C was found in VP-16 for MKN45 and KATO-III and in all of 5 drugs for AMC1. In colon cancer cell lines, this effect at 43C was found in all of 5 drugs for CCL188, in S-FU, CDDP, ADM for AMC5, in 5-FU, MMC, ADM, VP-16 for CloneA, KM-12C, and in 5-FU, CDDP, MMC, ADM for C106.
CONCLUSION
Hyperthermia itself had antitumor effect at 43C. Hyperthermo-chemotherapy had antitumor synergistic effect, especially at 43C.

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Comparison of Old and New TNM Classification of Gastric Cancer: Wan Sik Yu, Ho Young Chung, In Soo Suh; J Korean Cancer Assoc. 1999;31(5):939-945.

Abstract PDF: PURPOSE
We analyzed the appropriateness of the changes regarding the classification of gastric cancer in the fifth edition of the UICC TNMclassification of malignant tumors.
MATERIALS AND METHODS
Gastrectomy was performed in 727 patients with gastric cancer between 1990 and 1994. The pN, pM and stage of each patient was reclassified according to the 5th edition. The previous and present pN, pM and stage of each patient were compared.
RESULTS
Although ten cases of pNO were reclassified as pNX because the number of dissected regional lymph nodes was less than 15, there revealed a good correlation between old and new pN classification. Survival distribution according to the old pN classification identified significant differences among subgroups of patients. And this was true for the new pN classification. Nine pM1 patients who had involved hepatoduodenal lymph node were reclassified into pMO. Although 97 patients were down-staged and 30 patients were up-staged, comparison of stage according to two classifications revealed good correlation. Both survival distributions according to the new and old stage grouping identified significant differences among subgroups of patients.
CONCLUSION
The classification of lymph node metastasis and stage grouping in gastric cancer should be more scientific and rational in future revisions.

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The Study for the Postoperative Changes of Peripheral Lymphocytes and their Subsets as Immune Function in Advanced Gastric Cancer: Yoon Sun Joh, Yon Geul Joh, Min Young Cho, Sung Ock Suh; J Korean Cancer Assoc. 1999;31(5):946-954.

Abstract PDF: PURPOSE
This study evaluated the immunologic function of the postoperative lymphacytes and their subsets during 2 years after the curative resection of advanced gastric cancer.
MATERIALS AND METHODS
The peripheral lymphocytes and their subset in 64 advanced gastric cancer patients were preoperatively and postoperatively measured by using fluorescent conjugated monoclonal antibodies with flow cytometry. The monoclonal antibodies to T lymphocyte (CD3), B lymphocyte (CD19), helper-inducer cell (CD4), suppressor- cytotoxic cell (CD8), natural killer cell (CD16), and activated T cell (HLA-DR) antigens were used individually corresponding to T lymphocytes, B lymphocytes, helper-inducer T cells, suppressor-cytotoxic T cells, natural killer cells and activated T cells in post- operative periods (1, 3, 6, 12, 18, K 24 months). Their postoperative data were compared to the preoperative data in advanced gastric cancer.
RESULTS
On sequential measurements, peripheral lymphocytes were significantly decreased in postoperative 1 month than preoperative 1 day but they were gradually increased in postoperative 3, 6, 12, 18 and 24 months with significance. The B lymphocytes were significantly decreased in postoperative 3 and 6 months. NK cells were significantly increased in postoperative 3 months.
CONCLUSION
The two years postoperative changing patterns of peripheral lymphocytes and their subsets may not be improved in advanced gastric cancer patients which were undertaken curative surgery except lymphocyte.

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Role of Distal Pancreatectomy on the Prognosis of Gastric Cancer Patients Undergoing Total Gastrectomy: Sang Uk Han, Yong Kwan Cho, Bong Wan Kim, Tae Hee Kim, Myung Wook Kim; J Korean Cancer Assoc. 1999;31(5):955-963.

Abstract PDF: PURPOSE
A distal pancreatectomy was often simultaneously performed with splenectomy and total gastrectomy in the treatment of gastric carcinoma for complete removal of lymph nodes around the splenic artery. However, pancreatic juice leakage, subphrenic abscess, and postoperative diabetes were common complications in patients treated by pancreas resection. We performed a retrospective analysis to evaluate the role of distal pancreatectomy on the prognosis of gastric cancer patients.
MATERIALS AND METHODS
The effect of distal pancreatectomy on survival was studied by examination of the records of 120 patients who underwent splenectomy and total gastrectomy for gastric carcinoma with serosal invasion. Of these, 75 underwent pancreas preserving splenectomy and 45 underwent pancreaticosplenectomy. Prognostic factors and postoperative complications were evaluated according to the operation types.
RESULTS
The addition of distal pancreatectomy to splenectomy with total gastrectomy for patients with gastric cancer was not associated with severe complications. And patients underwent pancreaticosplenectomy showed similar survival as those underwent pancreas preserving splenectomy.
CONCLUSION
Distal pancreatectomy for the gastric cancer patients with suspected metastatic lymph nodes around the splenic artery could be recommended for the purpose of radical lymph node dissection.

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Clinical Analysis of Operative treatment of Remnant Gastric Cancer: Kwang Ho Lee, Jong Inn Lee, Ho Yoon Bang, Woo Chul Noh, Dae Yong Hwang, Dong Wook Choi, Nam Sun Paik, Nan Mo Moon; J Korean Cancer Assoc. 1999;31(5):964-971.

Abstract PDF: PURPOSE
Authors analyzed the clinico-pathologic parameters of 34 remnant gastric cancers to know the general behavior and prognosis of remnant gastric cancer.
MATERIALS AND METHODS
Medical records of 34 patients were reviewed retrospectively, who were diagnosed as remnant gastric adenocarcinoma and underwent operation in Korea Cancer Center Hospital from February of 1988 to March of 1998.
RESULTS
The incidence of remnant gastric cancer was 0.7% (34/4,904 cases). Sex ratio, male to female, was 2.8: 1. Mean age was 55 years of age. Diagnoses of primary lesion were 10 cases of benign lesion, 24 cases of malignant lesion. The operation for the remnant gastric cancer is total gastrectomy or extended total gastrectomy. The most common extended-resected organ was spleen (21 cases). The morbidity following operation of remnant gastric cancer were quite rare and treated conservatively. The overall five year survival rate was 11.3%.
CONCLUSION
Authors concluded that aggressive operation of remnant gastric cancer is warranted, as it is proved relatively safe and is the only option to lengthen patients survival and to alleviate their QOL (quality of life).

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A Phase 2 Study with Vinorelbine and Ifosfamide in the Inoperable Non - small Cell Lung Cancer: Moon Hee Lee, Young Jin Yoo, Soo Mi Bang, Gyung Hae Joung, Hyo Jin Kim, Dong Bok Shin, Soon Nam Lee, Seong Rok Kim, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(5):972-978.

Abstract PDF: PURPOSE
A phase II study of vinorelbine and ifosfamide combination chemotherapy in patients with advanced or recurrent non-small cell lung cancer (NSCLC) was conducted to assess response rate, response duration, and toxicites.
MATERIALS AND METHODS
Patients with advanced NSCLC who had no prior systemic chemotherapy were eligible. They have no central nervous system metastasis and recurrent or progressive disease after surgery or radiotherapy. Each cycle consisted of vinorelbine 25 mg/m' i.v. days 1 & 8, and ifosfamide 2 g/m i.v. days 1, 2 & 3 with Mesna and treatments were repeated every 21 days.
RESULTS
Forty patients with advanced or recurrent NSCLC were treated at multi center between March, 1997 and March, 1998. Six patients were not evaluable because five patients refused therapy after the first course and one patient was protocol violation. Of 34 evaluable patients, objective responses were seen in 11 (32.4%) patients (CR 0%, PR 32.4%). The median duration of response was 16.4 weeks. The median overall survival was 9.5 months. The toicities of this regimen were acceptable without treatment related toxic death.
CONCLUSION
We concluded that combination regimen of vinorelbine and ifosfamide was effective and tolerable in the treatment of advanced non-small cell lung cancer.

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Comparison of Rb and p53 Protein Expression with Stage and Grade as a Prognostic Value in Renal Cell Carcinoma: Hye Jeong Choi, Mi Jin Ko, Mi Jin Kim, Dong Sug Kim; J Korean Cancer Assoc. 1999;31(5):979-985.

Abstract PDF: PURPOSE
This study was performed to evaluate prognostic significance of Rb and p53 protein immunostaining in renal cell carcinoma. We investigated correlations between Rb, p53 immunostaining and nuclear grade and stage as prognostic factors of renal cell carcinoma.
MATERIALS AND METHODS
Subjects of this study were sixty-nine cases of renal cell carcinoma. We used indirect immunohistochemical methods in the formalin-fixed paraffin- embedded tissue (Rb: Pharmingen, USA; p53: Novocastra, UK). In staging and nuclear grading of the renal cell carcinoma, the American Joint Commitee on Cancer (AJCC) TNM system and Fuhrmans grading system were applied respectively.
RESULTS
According to Fuhrmans grading system, four cases were classified grade I, 15 cases were classified grade II, 13 cases were classified grade III, and 37 cases were classified grade IV. By AJCC TNM staging system, 29 cases were grouped stage I, 20 cases were grouped stage II, 15 cases were grouped stage III and five cases were grouped stage IV. In 55 cases (79% of all cases), Rb protein was expressed. Expression of Rb protein did not correlate with nuclear grade nor tumor stage. p53 protein was expressed in 17 cases (24% of all cases). p53 protein expression was frequently detected in high nuclear grade group (p < 0.05), but was not correlated with tumor stage.
CONCLUSION
Expression of Rb protein was not conelated with nuclear grade and stage. And expression of p53 protein was not correlated with stage, but it is correlated with nuclear grade. Thus immunohistochemical examinstion of p53 could be a histological prognostic factor.

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The Effect of Immunotherapy Based on Interferon - alpha in Advanced Renal Cell Carcinoma: Seung Hyun Jeon, Sung Goo Chang; J Korean Cancer Assoc. 1999;31(5):986-994.

Abstract PDF: PURPOSE
Recently in light of the development in immunology, interferon- e and inter- leukin-2 or combination therapy with anticancer drugs have been performed. This study aims to verify and compare the efficacy of therapies using interferon- a alone, interferon- a plus vinblastine, and interferon- a plus interleukin-2 plus 5-fluorouracil (5-FU) plus 13-cis retinoic acid (13cRA) in patients with advanced renal cell carcinoma.
MATERIALS AND METHODS
A total of 29 patients were randomly assigned to receive treatment with either interferon- a alone or interferon- a plus vinblastine or interferon- a plus interleukin-2 plus 5-FU plus 13cRA from December 1989 to May 1998. The most frequent metastatic sites were the lung, lymph nodes, bone, liver, and brain. We studied the response rates, survival period, and complications of each regimen.
RESULTS
Responses were achieved in 1 out of 1~5 patients (6.73?o) on interferon- a alone (partial responses lasting 13 months), 1 out of 9 patients (11.1%) on interferon- e plus vinblastine (partial responses lasting 25 months) and 1 out of 5 patients (20.0%) on interferon-a plus IL-2 plus 5-FU plus 13cRA regimen (partial responses lasting 14 months). The median durations of survival were 18, 33, and 23 months respectively. The overall response rate was 10.3% and overall median duration of survival was 19 months. The most common side effects were flu-like symptom such as fever, chills (93.1%), skin symptom such as erythema, pruritus (31.0%), G-I symptom such as nausea, vomiting (17.2%), netropenia (10.3%), abnormal LFT (10.3%), and thrombocytopenia (3.4%).
CONCLUSIONS
This study confirms the manageability and tolerability of several regimen used. There is no significant differences in response rates and survival duration among the regimens used in this study. The effective immunotherapy in patients with metastatic RCC should be evaluated by further studies of larger patients groups even though a minority of patients responded.

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The Effectiveness and Safety of DA-3030 ( rhG-CSF ) for Chemotherapy - induced Neutropenia: A Randomized Controlled Trial: Dae Ho Lee, Cheolwon Suh, Keunchil Park, Tae Won Kim, Jung Gyun Kim, Won Seog Kim, Won Ki Kang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(5):995-1002.

Abstract PDF: PURPOSE
We investigated the effectiveness and safety of DA-3030 for prophylatic use in patients receiving chemotherapy for malignant disease.
MATERIALS AND METHODS
Seventy cancer patients were randomized to receive chemotherapy alone (36 patients) or with DA-3030 administered (34 patients) after stratified block randomization according to chemotherapeutic regimen. DA-3030 was subcutaneously administered at the dose of 100 pg/m/day for 10 days from 24 hours after the completion of chemotherapy.
RESULTS
Of the 70 enrolled patients, 62 patients were evaluable. The neutropenia (absolute neutrophil count [ANC] <1,000/mm) occurred in 9 of 32 (28.1%) of the DA-3030 group and 21 of 30 (90.0%) of the control group, giving relative risk for control group of 0.154 (95% confidence interval [CI], 0.05 to 0.45; p-0.0001). Severe neutropenia (ANC 500/mm') occurred in 4 of 32 (12.5%) of the DA-3030 group and in 20 of 30 (66.7%) of the control group (relative risk for control group of 0.316 [95% CI, 0,18 to 0.55]; p=0.0001). The mean duration of neutropenic period (+/-standard error) was 1.13+/-0.34 days in the DA-3030 group and 6.73+/-0.69 days in the control group respectively, and was significantly shorter in the DA-3030 group (p<0.0001). And, there was higher nadir ANC in the OA-3030 group than that in the control group (p=0.0001); the mean nadir ANC was 2,547+/- 343/mm and 442+/-120/mm, respectively. The DA-3030 group had significantly higher incidence of myalgia in comparison to the control group (43.8% compared with 3.3%; p=0.001). However, it was tolerable and was easily managed by conservative therapy CONCLUSION: The use of DA-3030 was effective in preventing chemotherapy-induced neutropenia.

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5-Fluorouracil, Leucovorin ( FL ) Combination Chemotherapy in Advanced or Recurrent Colo - rectal Cancer: Jeong Hwan Cho, Hyuk Chan Kwon, Hyo Jin Kim; J Korean Cancer Assoc. 1999;31(5):1003-1010.

Abstract PDF: PURPOSE
We studied the effectiveness and toxicities of 5-fluorouracil+leucovorin, combination chemotherapy in advanced or recurred colo-rectal cancer patients, who didn't have previous chemotherapy and enrolled from August 1993 to July 1998.
MATERIALS AND METHODS
All patients were treated with leucovorin followed by 5-fluorouracil for 5 consecutive days every 4 weeks. Among 43 patients who were enrolled, 40 patients received treatment at least 2 courses, and they were evaluable. Male to female ratio was 21 to 19. In serum CEA level, 27 patients were greater than 5 ng/ml and 13 were less than 5 ng/ml. And primary site was colon in 21 patients and rectum in 19 patients.
RESULTS
The complete response rate was 7,5% and the partial response rate was 25%. The median survival duration was 14.7 months, the median response duration was 16.0 months, and median time to progression was 7.3 months. In the analysis of response, survival duration, time to progression according to various characteristics of patients, serum CEA level and liver involvement were revealed significant difference in survival duration, time to progression (p=0.0122, 00350 & 0.0202, 0.0123) on univariate analysis, but no significant difference on multivariates. Hematologic and non-hematologic toxicities were mild and tolerable.
CONCLUSION
This study indicates that the combination of 5-fluorouracil (370 mg/m) and leucovorin (20 mg/m) is effective and tolerable regimen in advanced or recurred colo-rectal cancer patients without previous chemotherapy.

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Role of PET Scan in Staging Work - up and Reevaluation after Therapy in Lymphoma: Young Jin Yuh, Chul Won Jung, Seock Ah Im, Dae Seog Heo, Yung Jue Bang, Seonyang Park, June Key Chung, Myung Chul Lee, Byoung Kook Kim, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(5):1011-1017.

Abstract PDF: PURPOSE
The authors evaluated the usefulness of the positron emission tomography (PET) with fluorine-18-tluorodeoxyglucose (8F-FDG) in initial staging, reevaluation after radical therapy and diagnosis of recurrence for non-Hodgkin's lymphoma, compaired to conventional imaging studies.
MATERIALS AND METHODS
FDG-PET (ECAT Exact 47, Siemens) and conventional chest X-ray and computerized tomography (CT) were studied in patients with non-Hodgkins lymphoma.
RESULTS
There were 17 patients (13 male, 4 female). Age was ranged from 18 to 62 years (median 49). By histological subgroup, diffuse large cell were 8 cases, peripheral T cell were 2 cases, diffuse mixed was 1 case, follicular mixed was 1 case, Burkitt's lymphoma was 1 case, Hodgkin's disease were 3 cases. The aims for PET were the initial staging work-up in 7 cases, the reevaluation of residual disease after radical therapy in 7 cases, the diagnosis of recurrence after complete remission in 3 cases. Between PET image and the conventional image, there were 3 cases with discrepancy, 1 case for initial staging work-up and 2 cases for the reevaluation of residual disease after radical therapy. Among the 3 cases with discrepancy, the 2 cases for the reevaluation of residual disease after radical therapy revealed that PET image reflects the involvement of lymphoma more accurately than the conventional image.
CONCLUSION
The visual analysis of FDG-PET would be helpful in determining the residual disease of lymphoma after radical therapy.

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Effect of Adjuvant Chemotherapy of Operable Breast Cancer : Survival and Prognostic Factor Analysis: Jeong Gyun Kim, Tae Won Kim, Je Hwan Lee, Sung Bae Kim, Cheolwon Suh, Kyoo Hyung Lee, Jung Shin Lee, Sei Hyun Ahn, Hyesook Chang, Sang Hee Kim, Woo Kun Kim; J Korean Cancer Assoc. 1999;31(5):1018-1026.

Abstract PDF: PURPOSE
Though the therapy using regimens similar to western countries has been done by medical oncologists in several different centers in Korea, there is no large scale study about the results of those adjuvant chemotherapy as in western country and it is not clear whether the results are same in Korean population as in western countries not only in overall outcome but also depending on various prognostic categories. It is important to review whether Korean patients would have equivalent results as in western countries or not when they were treated with the same standardized regimens. We examined the effect of adjuvant systemic chemotherapy on survival and analyzed prognostic factors.
MATERIALS AND METHODS
A retrospective analysis of survival and prognostic factors was done in 341 consecutive breast cancer patients who received curative operation followed by systemic conventional adjuvant chemotherapy between 1989 and 1996. The survival rate was compared using Kaplan-Meier method and Log-rank method. To evaluate an independent prognostic factors, Cox proportional hazard model was used.
RESULTS
After median follow up of 56 months (range 28 118 months), the mean disease-free survival (DFS) and overall survival (OS) was 81.0+/-2.7 and 91.5+/-2.6 months respectively. The 5-year DFS and OS rate was 61% and 77%, respectively. On univariate analysis, prognostic factors significant for DFS were tumor size (<2 cm vs. > 2 cm), hormonal receptor status, and histologic grade. Prognostic factors affecting both DFS and OS are as follows: age ((pound)40 vs 41-50 vs. (3)51), number of axillary node involvement, .and stage. Multivariate analysis showed that the number of axillary node involvement was the strongest adverse predictor.
CONCLUSION
The effect of adjuvant chemotherapy in Korean patients is not different from western countries and this report emphasizes the prognostic importance of number of axillary node involvement in breast cancer patients and necessity of intensive management of those with four or more positive nodes.

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Antiemetic Effect of Granisetron plus Dexamethasone for the Patients Refractory to Metoclopramide , Dexamethasone and Lorazepam ( MDL ): Se Hoon Lee, Dong Wan Kim, Kyun Hae Jung, Soo Mee Bang, Jae Ho Byun, Heung Moon Chang, Dae Seog Heo, Yung Jue Bang, Noe Kyeong Kim; J Korean Cancer Assoc. 1999;31(5):1027-1034.

Abstract PDF: PURPOSE
The combination of dexamethasone and granisetron provides effective prophylaxis in patients treated with high-dose cisplatin. We performed this study to evaluate the antiemetic effect of granisetron plus dexamethasone for the patients refractory to metoclo- pramide, dexamethasone, lorazepam (MDL) regimen.
MATERIALS AND METHODS
From 1996 to 1998, we administered the MDL regimen in patients who received high-dose cisplatin (more than 60 mg/m/day) for the first time. The granisetron plus dexamethasone were administered in the subsequent cycle for the patients refractory to the MDL regimen during the first or the second cycle of chemotherapy. Efficacies of treatment were assessed daily from days 1 to 5. Complete response was defined as the absence of vomiting episodes and major response as 1 or 2 episodes per day. Complete or major responses were considered effective.
RESULTS
Twenty patients received granisetron plus dexamethasone therapy. During the first 24 hours, complete and major responses were achieved in 75% and 15% respectively, thus it was effective in 90% of patients. For delayed vomiting (occurring during days 2 through 5), complete and major responses were achieved in 30% and 50% respectively, thus it was effective in 80%. Side effects included hiccups, headache, diarrhea, sedation, dizziness and insomnia, but discontinuation or dose adjustment was not needed.
CONCLUSION
The granisetron plus dexamethasone regimen was an effective antiemetic regimen for the patients refractory to the MDL regimen.

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Selective Cytotoxicity of the New Platnum ( 2 ) Complexes on Human Gastric Cancer Cell - lines and Normal Kidney Cells: Jee Chang Jung, Sung Goo Chang, Young Soo Rho; J Korean Cancer Assoc. 1999;31(5):1035-1043.

Abstract PDF: PURPOSE
Platinum coordination complex (cisplatin) has been currently used as one of the most effective compound in the treatment of various solid tumors. However, its use has been limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program has been aimed at developing drugs capable of diminishing toxicity and selective cytotoxicity.
MATERIALS AND METHODS
A new series of highly water soluble platinum (II) complexes Pt (II) [1,3-Bis (phenylthio) propane) (trans-l-1,2-diaminocyclohexane) (PC-1) and Pt (II) [1,3-Bis-(phenylthio) (propane)]-1,2-diaminocyclohexane (PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (.IR), ""C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity and nephrotoxi -cities of new Pt (II) complexes were tested against MKN-45 human gastric cancer cell- lines and normal kidney cells using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5- diphenyl tetrazolium bromide] assay for cell survival and proliferation.
RESULTS
PC-1 showed activity against MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cells, and the antitumor activity of this compound was comparable or superior to that of PC-2 and cisplatin. The nephrotoxicity of PC-1 and PC-2 were found quite less than that of cisplatin using MTT, [H] thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues.
CONCLUSION
Based on these results, this novel platinum (II) complex compound (PC-1) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

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Alfa - difluoromethylornithine Reduced Protein Phosphorylation in MCF-7 Human Breast Cancer Cells: Ji Young Lee, Byoung Kee Kim; J Korean Cancer Assoc. 1999;31(5):1044-1053.

Abstract PDF: No abstract available.

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Angiogenesis and Proliferating Cell Nuclear Antigen Index in Non-small Cell Lung Carcinomas: Chang Hoon Lee, Kang Suek Suh; J Korean Cancer Assoc. 1999;31(5):1054-1064.

Abstract PDF: PURPOSE
This study aimed to determine the relationship between angiogenesis and tumor cell proliferation evaluated by proliferating cell nuclear antigen (PCNA) in non-small cell lung carcinomas (NSCLCs) and to investigate the prognostic significance of the factors in them.
MATERIALS AND METHODS
Immunohistochemical staining for factor VIII related antigen, vascular endothelial growth factor (VEGF) and PCNA was performed using paraffin embedded blocks of 57 NSCLC cases. The results were correlated with some clinicopathologic parameters, including age, sex, TNM-T status, TNM-N status, stage, and histologic type.
RESULTS
Microvessel count (MC) was higher in squamous cell carcinoma group than in non-squamous cell carcinoma one (18.4+/-7.3 vs 14.6+/-9.9, p=0.043). PCNA index was higher in lymph node metastasis group than in non-metastasis one (42.1+/-8.9% vs 36.4+/- 14.6%, p=0.043). But the factors were not correlated with other clinicopathologic parameters. The relationship between VEGF expression and MC was significantly recognized (p=0.02), but that between VEGF expression and PCNA index was not. MC was positively correlated with PCNA index (r=0.547, p=0.005).
CONCLUSION
These findings suggest that both MC and PCNA index can be acted as useful indicators of prognosis in NSCLC, but tumor cell proliferation in NSCLC may be more concerned with any growth factor other than VEGF.

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Survival, Differentiation and ATM Phenotype of PC-12 Cells by Down - regulation of AT Gene: Ho Keun Yi, Soo Hee Chang, Dae Yeol Lee, Jung Soo Kim, Pyoung Han Hwang; J Korean Cancer Assoc. 1999;31(5):1065-1073.

Abstract PDF: PURPOSE
Ataxia Telangiectasia (AT) is a hereditary multi-systemic disease resulting from mutations of AT gene and is characterized by progressive neurodegeneration, cancer, immune system defects, and hypersensitivity to ionizing radiation. AT gene has a homologue sequence of PI3-kinase. The activity and cellular function of PI3-kinase in AT gene remains unclear. This study was undertaken to evaluate the function of AT gene through the effect on cell survival and differentiation by the inhibition of AT gene expression.
MATERIALS AND METHODS
NH2-terminal portion of AT gene was isolated from MCF-7 cells by RT-PCR. The isolated DNA fragment was ligated in reverse orientation in pcDNA3. This antisense ATM expression vector was transfected to PC-12 cells by calcium phosphate method, and the transformed cells were selected using G418 and immunohisto- chemistry. To analyze the cell survival and differentiation, cells were cultured in serum free medium supplemented with/without NGF. We performed the immunoprecipitation for the p53 induction of cells after ionizing radiation, and the FACS for the apoptosis of cells after the exposure of wortmanin.
RESULTS
PC-12 cells which down-regulated AT gene (like ATM, AT mutated) showed decreased survival and ceased differentiation with NGF. Also, PC-12 (ATM) cells showed increased apoptosis with wortmanin and reduced or delayed p53 induction after ionizingradiation.
CONCLUSION
Results obtained from these studies suggest that AT gene regulates survival and differentiation of PC-12 cells through PI3-kinase activity. It seems that apoptosis is induced by the inhibition of AT gene expression.

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Efficacy and Optimal Condition of Radiotherapy for Metastatic Epidural Cord Compression: Il Han Kim, Suk Won Park, Eui Kyu Chie, Sung Whan Ha, Charn Il Park; J Korean Cancer Assoc. 1999;31(5):1074-1080.

Abstract PDF: PURPOSE
This study was performed to evaluate the radiotherapy effects on metastatic epidural cord compressions.
MATERIALS AND METHODS
One hundred and thirty eight cases received palliative radio- therapy (30 Gy/10 fractions) with (15) or without (123) surgical decompression. Only 36% of cases were ambulatory before treatment and 34% of cases started treatment within 3 days after symptom onset.
RESULTS
Ambulation was possible after radiotherapy in 38% of all patients and in 73% of cases who was ambulatory before treatment. But the treatment made ambulation possible for 18% of cases who was paraplegic before treatment. Complete response rate, partial response rate, minimal response rate, and progression after treatment were as follows; 7%, 37%, 53%, and 3% respectively for the motor function, 8%, 32%, 58%, and 2% respectively for the sensory function, and 17%, 17%, 65%, and 1% respectively for the autonomic function. Responses were not influenced by the primary tumor site, histology, or involved level of the spine. Good responses were associated with starting treatment within 3 days after symptom onset.
CONCLUSION
Radiotherapy gave optimal palliative effects on metastatic epidural cord compression syndrome. Maximum responses or quality of life could be obtained from prompt treatment with awareness of this syndrome in cancer patients.

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Kaposiform Hemangioendothelioma Complicated by Kasabach - Merritt Phenomenon with Bone Involvement in an Adult: Sang Jeong Yoon, Young Seoung Kim, Dae Su Kim, Hee cheol Jang, Jeon Ok An, Ihn Seong Jo, Han Dong Yu, Tae Il Han, Tong Uk Kang; J Korean Cancer Assoc. 1999;31(5):1081-1085.

Abstract PDF: Kasabach-Merritt phenomenon does not occur with common hemangioma, rather it is associated with the more aggressive Kaposiform hemangioendothelioma and rarely with other vascular neoplasm. We report the case of an adult who was diagnosed as Kaposiform hemangioendothelioma complicated by Kasabach-Memtt phenomenon. This is the first report in Korea of an adult with Kasabach-Merritt phenomenon who has osteolytic changes of femur, pelvic bone, and lumbar spine.

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