Cancer Research and Treatment

Prognostic Significance of c-erbB2 , c-fos , p53 , Proliferating Cell Nuclear Antigen ( PCNA ) and Epidermal Growth Factor ( EGF: Seung Do Lee, Sung Uhn Baek, Chung Han Lee, Bang Hur, Man Ha Huh; J Korean Cancer Assoc. 1995;27(4):527-535.

Abstract PDF: To evaluate the prognostic significance of c-erbB2, c-fos, p53, PCNA and EGF in stage III gastric carcinoma, frequency of their expression was examined by immunohistochemical method in 206 cases of stage III gastric carcinomas with paraffin-embedded tissue specimens which were obtained surgically at the department of surgery, Kosin Medical College from 1984 to 1988. Survival rate and other clinicopathological parameters were analysed. Expression rates of c-erbB2, c-fos, p53, PCNA and EGF were 46.1%, 43.7%, 62.1%, 65.0% and 35.9% respectively. Correlation of expression was found betweer. EGF and c-fos, EGF and c- erbB2, and c-erbB2 and c-fos respectively. c-erbB2 expression was more frequently observed in intestinal type, well or moderately differentiated carcinomas than diffuse type, poorly differentiated or mucinous types(p<0.05). Similarly EGF expression rate was high in intestinal type and low in mucinous or signet ring cell types(p<0.05). Five year survival rates of positive cases and negative cases were 27.4% and 23.9% in c-erbB2, 27.7% and 23.9% in c-fos, 24.0% and 27.8% in p53, 25.1% and 26.4% in PCNA and 20.5% and 28.9% in EGF respectively. There were no significant differences between positive cases and negative cases in survival rates. When the above factors and conventiona1 prognostic fectors such es tumor depth(t3, t4), lymph node invasion(n0, nl, n2), number of positive nodes(l-3, 4-6, 7- ), Laurens types, were en- tered simultaneously into the Cox regression model, number of positive nodes, and RGF expression emerged as independent prognostic factors(p=0.0004, p=0.043 respectively).

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Clinical Significance of Neopterin in Gastric Cancer Pancer Patients: Woo Song Ha, Hyun Un Cho, Tae Sub Jung, Se Yeop Kim, Jin Sang Choi, Soon Tae Park, Young Chae Kim; J Korean Cancer Assoc. 1995;27(4):535-544.

Abstract PDF: Neopterin can be used as an objective index of disease activity and response of therapy. In malignant diseases, the degree of neopterin elevation is a measure of clinical activity, and serves as a measure of extent of disease in some tumors. Since the analysis of urinary neopterin in gastrointestinal cancer patients is important in diagnosing malignancy, a method has been developed for its rapid and sensitive separation and quantitation using high perform- ance liquid chromatography(HPLC) on reverse phase. The aim of this study was to evaluate the correlation of the clinical and pathologic stage in gastric cancer and the neopterin leveL Using HPLC method, urinary levels of neopterin related to creatinine were determined for 40 gastric cancer patients(December, 1993--5eptember, 1994). The samples were the patients first morning urine(1 ml) and added 25 mg of disodium ethylenediamine tetraecetate and stored at 20'C in the dark state. Then samples were preparated with 1%, 12% KI and ascorbic acid, after then centrifuged at 3,000 rpm for 15 minutes. The supernatant was injected into HPLC. The other method was the use of commercially available Sep-Pak Cl8 cartridges(Waters Asso.). With this method, urinary neopterin level was measured in gastric cancer patients with stage IV and recurrence. The data was analysed with students t-test and it was statistically significant when p value was lower than 0.05. The results were as follows; in TNM classification, the neopterin/Cr. level was positively correlated with advanced stage(p<0.05). In WHO classification, the neopterin/ Cr. level of poorly differentiated group was higher than well differentiated group(p<0.05). In Mings classification urinary neopterin level of infiltrative type group was higher than that of expanding type group(p<0.05). In Laurens classification the neopterin/Cr. level of diffuse type group was higher than that of intestinal type group(p<0.05). In conclusion, there was a positive correlation between neopterin/creatinine ratio and the stage af gastric cancer and the severity of gastric cancer(Severity means advanced state in Pathologic classification. For example, stage II than stage I, stage III than II, stage IV than stage III in TNM classification, poorly differentiated than well differentiated in WHO classification, infiltrative type than expanding type in Mings classification, diffuse type than intestinal type in Laurens classification). So urinary neopterin levels were closely related to the extent of the lesion and severity of the disease.

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Expression of HLA Class 1 and 2 in Gastric Cancer and Adjacent Mucosa: Young Jin Kim, Ji Yun Kook, Hyun Jong Kim, Shin Kon Kim, Sang Woo Juhng; J Korean Cancer Assoc. 1995;27(4):544-550.

Abstract PDF: Expression of HLA-ABC and HLA-DR was observed in 24 fresh surgical specimens of both gastric cancer and adjacent mucosa with flow cytometry after staining with monoclonal antibodies. In gastric cancer tissues, the HLA-ABC positive cells were 79.9+-5.3% and the HLA-DR positive cells were 75.2+-t5.1%. These ratio of HLA-ABC and HLA-DR positive cells in gas- tric cancer tissues was higher than those in normal adjacent mucosa ( HLA-ABC; 68.0+-6.6 %, HLA-DR; 62.0+-6.2%). In metastatic gastric cancer, HLA-ABC was higher than normal mucosa in most cases. However, HAL-ABC expression in all cases with peritoneal seeding was less than normal mucosa. In stage I gastric cancers, HLA-ABC and HAL-DR positive cells were more than advanced gastric cancers. HLA-ABC positive cells were more com- mon in well and moderately differentiated gastric cancers than in poorly differentiated cancers (85.7+-26.4%: 76.7+-27.1%). The HLA-DR positive cells were less in aneuploid cancers than in diploid cancers (70.2+-28.1%: 87.8+-7.9%). We established method to quantitativ . analysis of HLA expression in tissue. Expression of HLA-ABC & DR were higher in gastric cancer tissues than in normal mucosa. Among the tumors, the HLA-ABC expression was higher in stage I, well differentiated and small cancers, and HLA-DR in diploid and nonmetastatic cancers.

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Prognostic Significance of Proliferating Cell Nuclear Antigen ( PCNA ) Expression in Patients with Colorectal Carcinoma: Il Kwon Jung, Hong Jo Choi, Sang Soon Kim, Sook Hee Hong; J Korean Cancer Assoc. 1995;27(4):550-559.

Abstract PDF: Proliferating cell nuclear antigen(PCNA) is an auxiliary protein of DNA polymerase 8 and is considered to correlate with the proliferative state of cells. If such a biologic marker in colorectal cancer tissue correiates with recurrence and poor survival, it would offer a rationale for planning aggressive adjuvant therapy. Authors investigated the prognostic significance of proliferative activity in cancer cells in patients with colorectal carcinoma using PCNA immunohistochemical analysis. An anti-PCNA monoclonal antibody (PC 10) was used to measure proliferation indices in neoplastic colorectal tissues of 61 patients with the different clinical outcomes. The correlations of PCNA labeling index (PCNA LI) with various clinicopathologic factors, recurrence and prognosis were studied. The results obtained were summarized as follows; 1) The PCNA LI become higher as the histologic differentiation decreased and the Dukes stage increased, both of which were statistically significant (p=0.0133 and 0.0001, respectively). 2) The rate of disease recurrence after curative resection (53 cases) was significantly higher in patients with high PCNA LI (PCNA LI>=50) as compared with those with low PCNA LI (PCNA LI<50) (44.4% vs. 14.3%, p= 0.022). 3) In patients with high PCNA LI, prognosis (2-year survival) was significantly poorer than in those with a low index (31.8% vs. 58.6%, p<0.05). As a result of this study, PCNA labeling index as determined by PCNA immuno- histochemical analysis is suggested to be correlated well with the histologic differentiation and tumor stage and to be an effective predictor in colorectal cancer. The PCNA analysis for biologic heterogeneity of patients with colorectal cancer may be useful in the prognostic grouping of patients and planning prophylactic therapy.

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Effects of Retinoic Acid on p53 Protein , Ki - 67 and PCNA / Cyclin Expression in PLC / PRF / 5 Cells: Dae Gon Kim, Cheol Kwon, Wan Hee Yoo, Yee Yup Kim, Deuk Su Ahn; J Korean Cancer Assoc. 1995;27(4):559-570.

Abstract PDF: Retinoic acid(RA), known to have antiproliferative and differentiation-inducing effecte on cancer cells, was examined to evaluate its potential as a chemotherapeutic agent for hepatocellular carcinoma. The treatment of PLC/PRF/5 cells with RA(l0 pM for 8 days)resulted in inhibited growth by 23.8% as compared to that of control. The decreased cell growth rate was started 2 days after RA addition. We examined the level of expressions of the mutated p53 protein, the Ki-67 antigen, and the proliferation cell nuclear antigen(PCNA)in cultured PLC/PRF/5 hepatocelluar carcinoma cells before and after RA treatment. The mutated pM is thought to be involved in oncogenesis of human cancers, and the expressions of the Ki-67 and the PCNA are used to evlauate tumor cell kinetics. The e#xpression of p53 protein was not inhibited significantly in PLC/PRF/5 cells by treatment with 10 M RA in Go/Gi, S, or G/M phase fraction, as detected by immunocytochemical staining using the monoclonal antibody PAb 180 which recognizes both the wild and the mutated p53 protein. Also no significant increase of expression was observed using the monoclonal antibody PAb 240 which binds only the mutated p53 protein. RA treatment increaaed Go unstained fraction from 0.36+-0.06% to 0.7+-0.19% and decreased Ki-67 antigen expresaion significantly from 51.2+0.8% to 46.9+0.4%(p=0.03) in G phase, 14.8 0.5% to 1l.30.5%(p=0.03) in S phase respectively, but increased the fraction of GgM phase from 33.4+-1.1% to 36.8+-1.4%(p=0.02). PCNA expression was also dropped by RA treatment from 50.4+-1.5% to 42.8+-0.3%(p=0.01) in Gw G, fraction, 14.7+-0.5% to 11.9+-0.4%(p=0.02) in S phase, increased G/M phase fraction from 31.3+-l.2% to 42.2+-0.6%(p=0.008). These results suggested that RA may have anticancer effect through the inhibitiion of Ki-67 and PCNA expression in similar cell cycle phase without affecting the expression of mutant p53 protein in PLC/PRF/5 cells was observed. In addition, cell cycle anaysis suggested that RA induced en arrest of G, progression to G, and S phase.

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Detection of bc12 & bax Expression in the Head & Neck Cancers: Chan Seung Hwang, Jong Ouck Choi, In Sun Kim; J Korean Cancer Assoc. 1995;27(4):570-578.

Abstract PDF: Programmed cell death(apoptosis) is a distinctive form of cell death manifested by characteristic chromatin condensation and DNA fragmentation, whose function is the deletion of cells in normal development, organogenesis, immune function, and tissue growth, but which can also be induced by pathologic stimuli. The bc12 shows the unique functional role of blocking apoptosis independent of affecting proliferation, appears to constitute a member of a new category of oncogenes: regulators of programmed cell death. The bax homodimerizes and forms heterodimers with bc12 in vivo. Overexpressed bax accelerates apoptotic death, and the ratio of bc12 to bax determines survival or death following on apoptotic stimulus. The purposes of this study were to examine the expression of bcl#l & bax in the head & neck cancers according to histologic types & cellular differentiation rate, to examine the relationship between bcl2 expression and bax expression in the same specimens. For these purposes, paraffin-embedded tissues were subjected to immunohistochemistry techniques. Following results were obtained: 1) The bc12 was detected in 20(100%) out of 20 cases of undifferentiated carcinoma, 15(57.7 /) out of 26 cases of non-keratinized squamous cell carcinoma, 4(16.66%) out of 24 cases of keratinized squamous cell carcinoma, 6(50%) out of 12 cases of malignant lymphoma. 2) The bax was detected in 23(95.83%) out of 24 cases of keratinized squamous cell carcinoma, 18(69.23%) out of 26 cases of non-keratinized squamous cell carcinoma, 9(45%) out of 20 cases of undifferntiated carcinoma, 5(41.67%) out of 12 cases of malignant lymphoma. 3) The positive rate of bax expression was more higher in 29(78.38%) out of 37 cases negative for bc12 than 26(57.78%) out of 45 cases positive for bc12. In conclusion we found that the higher the expression of bc12, the poorer the cellular differentiation rate, the higher the expression of bax, the better the cellular differentiation rate in the head & neck carcinomas. And also we found that the bc12-bax expression rate was inversely praportional in same specimens of the head & neck cancers.

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A Clinical and Experimental Study on Angiogenesis of Breast Carcinoma: Yeob Lee, Dong Won Kim, So Yeung Jin, Dong Wha Lee; J Korean Cancer Assoc. 1995;27(4):578-593.

Abstract PDF: The process of angiogenesis is a prereguisite for normal cell growth and differentiation. Neovascularization might also be important for tumor growth in the host tissue and for the establishment of growth in distant target tissue. Many studies have suggested that the presence of neovascularization (microvessel density) can be used as a biologic marker" for the prediction of subsequent metastasis or mortality in breast cancer patients. To evaluate the relationship between microvesse1 density and other known prognostic indicators in breast carinoma, we performed immunoperoxidase staining using CD31 (IC70, Dako) on 80 cases of formalin fixed human breast cancer tissue, and counted microvessel density(MVD) per xl00 field in the most active areas of neovascularization. Also mamma- ry tumors were experimentally induced by feeding of 9,10-dimethyl-1,2-benzan-thracene (DMBA) to female Syrague-Dawley rats, and then the angiogenic activity was observed during neoplastic transformation by immunoperoxidase staining for factor VII:-related antigen. The mean value of MVD was 78.70+23.95 in the node negative group, and 91.2326.18 in the node positive group. Thus there was a significant (p=0.0285) association of MVD with axillary nodal status. However, there was no association between MVD and other prognos- tic factors, i.e, estrogen and progesterone receptors, age, tumor size, and nuclear grade. Multivariate analysis by Cox's proportional hazard model disclosed that MVD, sge of patients, axillary nodal status and nuclear grade could influence patients prognosis. Breast masses developed in 68% (25/37) of DMBA treated rats, and revealed fibroadenomatous hyperplasia, adenomatous hyperplasia (hyperplastic alveolar nodule) and adenocarcinoma with increased neovascularization depending on size and duration. This study concludes that the breast masses in DMBA treated rats can be used as an experi- mental animal model of neoangiogenesis in breast cancer.

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Prognostic Signicance of the CD44 and Matrix Metalloproteinase 3 ( Stromelysin 3 ) Expression in Breast Cancer: Hye Rim Park, Jin Hee Sohn, Young Euy Park; J Korean Cancer Assoc. 1995;27(4):593-602.

Abstract PDF: Expression of the CD44 and matrix metalloproteinase 3 were examined in 43 cases of breast carcinoma. Immunohistochemical staining with CD44 antibodies demonstrated dif- fuse cytoplasmic positivity in tumor cells of intraductal and invasive carcinoma. Matrix metalloproteinase 3 was present in invasive cancer cells and surronding stromal cells. Expression of the CD44 and matrix metalloproteinase 3 were moderately correlated. Expression of the CD44 was associated with the large size of primary tumor(>=2cm), the histologic grade by Bloom-Richardson, the presence of metastatic node, and the clinical stage. Overall five-year survival rate in 43 patients was 74.0+-9.6% and the disease free survival curve showed significant difference according to the expression of CD44. However, the expression of matrix metalloproteinase 3 was not associated with variable prognostic factors and disease free survivaL From this study, it is concluded that expression of the CD44 and matrix metalloproteinase 3 were associated with invasion of breast cancer and expression of the CD44 could be used as a prognostic indicator in breast cancers. However, the expression of matrix metal- loproteinase 3 had the limited value.

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Breast Cancer during Pregnancy and Lancation: Seong Heum Park, Jeoung Won Bae, Eun Sook Lee, Bum Hwan Koo; J Korean Cancer Assoc. 1995;27(4):602-608.

Abstract PDF: 7 patients with breast cancers during pregancy and loctatian seen at Korea University hospital during a 5 year period(1989-1993) were presented. They were found among 377 cases of breast cancers we experienced during the same period, for an incidence of 1.9%. Ages ranged from 25 to 31 years with an average of 31.9 years. A disproportionately long interval of average 79 days between the discovery of a lump in the breast by the patient and the actual diagnosis of the breast carcinoma was impressive. Three patients were diagnosed during the pregnancy and others after delivery. Modified radical mastectomy (Auchincloss) was performed for 6 pa- tients with operable breast cancer. One patient with locally advanced breast cancer was on preoperative chemotherapy, but she refused the therapy on the way. There were one stage I, two stage IIa, one stage IIb, two stage IIIa and one stage IIIb tumors. The literature was reviewed in a attempt to define most appropriate treatment for these oatients. Answers to traditional guestions about breast cancers during pregnancy and lactation are becoming less traditional. Radical mastectomy is almost as curative for pregnant patients with operable cancers as for others and presents little chance of fetal loss. Therapeutic abortion does not improve the chance for cure, nor does prophylactic castration. For inoperable or disseminated cancer, effective endocrine ablaiton or chemotherapy requires therapeutic abortion. Pregancy subsequent to mastectomy neither promotes nor diminishes the chance of continued maternal wellbeing. If age and study of disease are taken into account, pregnancy itself seems to have a neg- ligible influence on prognosis.

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Neoadjuvant Chemotherapy in Locally Advanced Non - Small Cell Lung Cancer: Hai Jung Cho, Kyoung Sang Shin, Sang Ki Park, Ae Kyung Kim, Jong Jin Lee, Nam Jae Kim, Jee Won Seo, Ju Ock Kim, Seung Pyung Lim, Sun Young Kim; J Korean Cancer Assoc. 1995;27(4):608-620.

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A Phase 2 Study of VP-16 , Ifosfamide Cisplatin ( VIP ) Combination Chemotherapy for Small Cell Lung Cancer: Rok Yun Lee, Young Suk Park, Yun Chang Han, Ho Joong Kim, In Gyu Hyun, Ki Suk Jung, Jung Ae Rhee, In Sook Woo, Young Iee Park, Keun Chil Park, Duk Jhe Shun, Sang Gyu Choi, Do Hoon Oh, Hoon Sik Bae; J Korean Cancer Assoc. 1995;27(4):620-630.

Abstract PDF: We conducted a phase II trial combining etoposide(VP-16), ifosfamide(IFM), and cisplatin (DDP) in previously untreated patients with histologicaliy confirmed small cell lung cancer (SCLC). Each cycle consisted of VP-16 100mg/m(2) i.v. days 1-3, IFM 1,000mg/m i.v. days 1-2 with mesna, and DDP 100mg/m(2) i.v. day 1. Cycles were repeated at 3 week intervals. Patients of limited SCLC received chest irradiation concurrently with the third cycle of VIP chemotherapy. Patients with complete remission received prophylactic cranial irradiation after the 6th cycle of chemotherapy. Thirty-seven patients were enrolled. Ages ranged from 34 to 76(median 61 years); 32 were male, and 5 female. Nineteen patients had limited disease(LD) and 18 extensive disease(ED). Three patients were not evaluable because of lost to follow up(2 patients) and early death(l patient). Of 34 evaluable patients, 13 patients(LD; 12, ED; I) had complete re- missions, 19 patients(LD: 6,ED; 13) had partial remissions and overall remission rate was 94 %. The median remission duration was 8.6 months(LD; 12.5months, D; 5.1months)..Disease free survival was 14.5 months in patients achieved complete remission. The median dura- tion of follow-up was 21 months (1 to 39 months), and overall median survival was 12.8 months(16.1 months for LD, 8.2 months for ED). Hematologic side effects(WHO Gr>=2) of evaluable 168 cycles of chemotherapy were anemia in 10 occassions(6%), leukopenia in 35 occassions(21%), thrombocytopenia in 27 occassions(16%). Nonhematologic side effects(WHO Gr>=2) included alopecia(91%), nausea and vomiting (80%), peripheral neuropathies (31%), and stomatitis (11%). In conclusion, VIP combination chemotherapy seems to be a safe, effective, and well-tolerated regimen in SCLC.

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The Role of Radiation Therapy in Multiple Myeloma: Mi Ryeong Ryu, Ki Mun Kang, Hong Seok Jang, Sei Chul Yoon, Hoon Kyo Kim, Kyung Shik Lee, Kyung Sub Shinn; J Korean Cancer Assoc. 1995;27(4):630-637.

Abstract PDF: Purpose
This study is to define the role of radiation therapy for palliation in the management of multiple myeloma. Methods & Materials: Thirty five patients with multiple myeloma received palliative radiotherapy at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College between December 1983 and September 1993. Of the eighty- four treated sites, eighty evaluable sites were analysed retrospectively. The male to female ratio was 1.3:l. Age at diagnosis ranged from 36 to 76 years with a mean of 58 years and the follow-up period ranged from 3 to 134 months with a median of 26 months. The most common treated sites were spine(50%), rib(19%), and pelvis(11%) in decreasing order. The most common symptom was pain(93.7%). Pain was graded as mild, moderate, and severe degree of pain according to clinical classification of pain intensity by WHO. Pain relief following radiation therapy was assessed as complete, partial, or no relief of symptom by analgesic use and change of pain grade. In the case of neurologic impairment, treatment response was assessed by neurologic examination. Results: Total tumor doses ranged from 4 to 35 Gy, with a mean of 19.4 Gy. Symptom relief waa obtained in 76(95%) of 80 evaluable symptomatic sites. No clear dose-response relationship could be demonstrated in this study(p>0.05). The likelihood of symptom relief was not influenced by the location of the lesion, use of concurrent chemotherapy, serum hemoglobin level, serum calcium level, or initial pain grade(p>0.05). Of the 76 responding sites, 9 sites(11.8%) relapsed after median symptam-free interval of 22 months(range, 2-75 months). Neither the probability of relapse nor the time to relapse was related to the radiation dose(p>0.05). Retreatment of relapsing sites provided effective palliation in all cases. Conclusion: Low dose local external radiation therapy provides effective palliation in the management of multiple myeloma.

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Immunohistochemical Expression of Keratin Subtypes in Tumors of Uterine Cervix: Keun Hong Kee, Sung Chul Lim; J Korean Cancer Assoc. 1995;27(4):637-646.

Abstract PDF: Keratin is a major class of intermediate filaments in epithelial cells, and comprises a group of at least 20 different multigene-derived proteins. It is expressed in different epithelia with specific combinations. The materials for this study consisted of chronic cervicitis, reserve cell hyperplasias, squamous metaplasias, cervical intraepithelial neoplasias, squamous cell carcinomas, and adenocarcinomas. All cases were performed by immunohistochemical stains for panel of monoclonal cytokerain(CK) antibodies. Also, some cases were examined by immunoelectron microscopy. The basal cells of exocervix were positively stained for CK 5/6, 8, 14, 18 and 19. The intermediate and superficial cells of exocervix were positive for CK 1, 5/6, 7, 8, 13 and 18. The endocervical columnar cells were positive for CK 7, 8, 18 and 19. The reserve cells were positively stained for CK 5/6, 8, 14, 18 and 19. The metaplastic cells were positively stained for CK 1, 5/6, 7, 8, 10 and 18. The dysplastic cells were positively stained for CK 5/6, 10, 13, l4, 18 and 19. The keratinizing squamous cell carcinomas were positively stained for CK 5/6, 8, 14 and 19. The nonkeratinizing squamous cell carcinomas were positively stained for CK 1, 5/6, 10, 13, 14 and 19. The adenocarcinomas were positively stained for CK 5/6, 7, 8, 10, 14, 18 and 19. In conclusion, individual normal epithelial cells and numerous tumor cells of the uterine cervix have two or more different subtypes of keratin. Keratinizing squamous cell carcinomas show similar staining pattern to those of reserve cells or basal cells. The cytokeratin subtypes of dysplastic cells are similar to those of nonkeratinizing squamous cell carcinomas.

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Intracavitary Therapy with Bleomycin for The Treatment of Malignant Pleural and Pericardial Effusion: Hun Kwan Lim, Myung Lyel Lee, Jin Woo Jeon, Seong Gyu Park, Jong Ho Won, Seung Ho Baik, Dae Sik Hong, Hee Sook Park; J Korean Cancer Assoc. 1995;27(4):646-653.

Abstract PDF: Pleural effusions caused by malignancy occur commonly and are generally a manifestation of the advanced disease. Regardless of the underlying tumor type, mertality within 30 days has been reported to be as high as 50%. Respiratory insufficiency due to malignant pleural effusion often demands palliative management of the effusion. Malignant pericardial effusion is one of the most common causes of cardiac tamponade. Bleomycin and tetracycline have been widely used as sclerosing agents in malignant pleural effusion in North America and Europe. Bleomycin is less often used in the malignant pericardial effusion but is efficacious. Our study was begun to assess the effect and safety of bleomycin pleurodesis/pericardiodesis. Prospectively assigned twenty patients with malignant effusion(pleural effusion: 15, pericardial effusion; 5) to this therapy. Their age ranged from 19 to 69 years with a median of 47 years. Pri- mary sites were lung in 10, colon in 2, stomach, breast, uterine cervix, leg(sarcoma), mediastinum(malignant lymphoma), kidney in 1 each and unknown in 2(malignant melanoma and adenocarcinoma). The responses were categorized as objective response or failure. Twelve patients(70.5%) showed an objective response(complete response: 47% (8 cases), partial response: 23.5% (4 cases) out of 17 evaluable cases and the duration ranged from 5 to 78 weeks with a me- dian of 16 weeks. The response rates of malignant pericardial effusion and pleural effusion were 100/ and 61.5% respectively. Chest pain(10/17), and fever and/or chill(9/17) were the most common side effects. Other untoward effects included vomiting(4/17), anorexia(3/17), hypersensitivity(1/17), pyothorax(l/17). We conclude that bleomycin pleurodesis and pericardiodesis in malignant effusion can be performed safely and show good treatment effects, especially in maiignant pericardial effusion.

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Effect of Crude Extract from Shark Cartilage on Angiogenesis Induced by Malignant Tumor Implanted to the Chorioallantoic Membrane of Chick Embryo and ICR Mouse: Young Bae Kim, Dong Hwan Shin, Min Young Kim, Tae Sook Hwang; J Korean Cancer Assoc. 1995;27(4):653-671.

Abstract PDF: Malignant tumors are almost invariably associated with angiogenesis, which could be inhibited by a number of agents including crude extract from shark cartilage(CESC). The experiments presented here were designed to morphologically evaluate the effect of CESC on both proliferation of malignant tumor and microvessels thereof by means of chorioallantoic membrane(CAM) assay and implantation of malignant tumor. First, CAM assay was performed to evaluate the antiangiogenic effect of CESC. CESC was infused into F9 murine embryonal carcinoma implanted into CAM and peritoneum of ICR mouse with Sarcoma 180 cells implanted in subcutis. Quantitative evaluation of angiogenesis was attempted by counting new microvessels within the tumor of both groups. In addition, cytokinetic study of new microvessels was also performed using immunohistachemical staining of proliferating cell nuclear antigen(PCNA) to endothelial cells. The CAM assay for CESC showed distinct inhibitory effect on new microvessels but not on preexisting blood vessels. There was obvious decrease in density of new vessels growing towards F9 murine embryonal carcinoma implanted into CAM in the experimental group as compared with the control group. The weight of F9 murine embryonal carcinoma implanted tend to be greater in the control group than in the experimental group. Likewise, the weight of Sarcoma 180 implanted into ICR mouse initially increased slowly but later more rapidly in the control group than in the experimental group reflecting that the density of microvessels in the later group was much more decreased, -which was confirmed on tissue sections. PCNA labelling index of proliferating endothelial cells within Sarcoma 180 implanted tended to be decreased more in the experimental group than in the control group as was that of endothelial cells in F9 murine embryonal carcinoma implanted into CAM. These results indicate that CESC can inhibit angiogenesis and thus suppress proliferation of malignant tumor. It follows that selected extract of shark cartilage accounting for inhibition of angiogenesis could suppress tumor growth and passibly prevent even tumor metastasis when considering the essential step of angiogenesis in process of metastasis in general.

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The Effect of Hydralazine on Hyperthermic Treatment of C3H Mouse Fibrosarcoma: Woo Yoon Park, Sung Whan Ha, Charn Il Park; J Korean Cancer Assoc. 1995;27(4):671-680.

Abstract PDF: Hypoxic cells comprise l0~20% of tumor cells and are more sensitive to hyperthermia. By decreasing tumor blood flow artificially and thus increasing the hypoxic fraction in the tumor, the cytotoxic effect of hyperthermia can be increased. Hydralazine is an antihypertensive drug and its main mechanism is relaxation of the vascular smooth muscle of arterioles rather than veins. Administration of hydralazine causes a decrease in vascular resistance and an increase in blood flow in normal tissue, but since the vasculature of tumor is not responsive to such a drug, blood flow in tumors is decreased because of steal phenomenon. Thus the hypoxic fraction in the tumor is increased, and the tumor becomes more sensitive to hyperthermia. Therefore, to evaluate the hydralazine effect on hyperthermia, the tumor growth delay was investigated and the change in the hynoxic fraction of the tumor was estimated using C3H mouse fibrosarcoma(FSaII) with hypoxic fractions af usual range. In 6 mm FSaII tumors grow- ing in the dorsum of the foot, administration af 5 or l0 mg/kg of hydralazine was followed by 43`C, hyperthermia for 60 minutes. Tumor growth times (TGT) to reach a tumor volume of 500 mm(2) were 7.11+-0.84 days and 7.44+- 1.13 days for controls and 10 mg/kg of hydralazine only. TGTs for hyperthermia alone and administration of 5 or 10 mg/kg of hydralazine followed by hyperthermia were 10.34+-2.17 days, 13.38+-1.82 days and 14.47+- 0.67 days, respectively. Elongation of tumor growth delay by administration of 5 or l0 mg/kg of hydralazine in addition to hyperthermia were statistically significant (0.025

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A Case of Metastatic Adenocarcinoma of Urinary Bladder from Gastric Cancer: Kun Hoon Song, Joo Young Yang, Hee Yong Moon, Jun Hyun Song, Young Myung Moon, Jin Kyung Kang, In Suh Park, Tack Lee, Soon Won Hong; J Korean Cancer Assoc. 1995;27(4):680-686.

Abstract PDF: The incidence of metastatic bladder cancer from a distant organ is quite rare. A sixty five-year old man visited our hospital complaining of painless gross hematuria. He had undergone radical subtotal gastrectomy with lymph node dissection and 6 cycles of postop- erative adjuvant chemotherapy for advanced gastric carcinoma ten months earlier. Cystogram and abdominopelvic CT scan howed contrast enhanced mass mainly located in superoanterior aspect of bladder walL The upper endoscopy and abdominal CT scan revealed no evidence of recurrence in primary site. Bleeding from bladder mass was successfully controlled with electrocauterization under direct vision of cystoscopy. This case was diagnosed as metastatic adenocarcinoma of urinary bladder from gastric cancer by cystocopic biopsy and cytologic examination of urine. The cell type and degree of differentiation was exactly identical between the tissue obtained from stomach during gastric cancer surgery and that obtained from blad- der by cystoscopic biopsy. Therefore, when urologic symptoms are newly developed to the patients who had malignancy of digestive organ, metastatic malignancy of urogenital organs should be considered, even though it is very rare. Herein, we report a case of metastatic urinary bladder cancer from advanced gastric carcinoma which occurred ten months after radical surgery.

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A Case of Malignant Testicular Lymphoma with Diffuse Bilateral Renal Involvement: Hyug Chan Suh, Sug Kyun Shin, Young Goo Song, Heon Soo Kim, Kwang Hwa Park, Se Joong Kim, Hugh Chul Kim; J Korean Cancer Assoc. 1995;27(4):686-692.

Abstract PDF: Involvement of testis by malignant lymphoma is rare in young age, comprising only 2% of testicular cancers under 50 years old and 25% of over 50 years old. Testicular lymphoma is frequently bilateral and has a poor prognosis. Testicular lymphoma has a propensity to involve the skin, the central nervous system, Waldeyers ring and adjacent structures. Renal involvement in lymphoma is often manifested as multinodular masses, whereas diffuse renal infiltration is less freguent. Most often, renal involvement of malignant lymphoma is asymptomatic. Of the reported cases of renal insufficiency secondary to diffuse renal infiltration with lymphoma, few have presented with acute renal failure. We present a patient with acute renal failure secondary to diffuse bilateral renal infi1tration and unilateral testicular non-Hodgkin's lymphoma.

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Acinar Cell Carcinoma of the Pancreas - A case report -: Soo Young Chung, Ik Yang, Yul Lee, Hai Jung Park, Hye Kyung Ahn; J Korean Cancer Assoc. 1995;27(4):692-696.

Abstract PDF: Acinar cell carcinoma in pancreas is uncommon and occurs in less than 2% among the epithelial non-endocrine pancreatic tumors. Acinar cell carcinoma is usually seen in the elderly patients and shows poor prognosis due to frequent metastasis. A 59 year old man was admitted because of indigestion and abdominal distension. A large, irregular, marginated, heterogeneous and hypodense mass with internal necrosis in pancreas was the characteristic CT feature of acinar cell carcinoma in pancreas. Celiac arteriogram showed a central hypovascular mass with sweeping of left gastric artery. Superic; mesenteric arteriography showed tortuous neovascularity along the peripheral portion of mass. Gross specimen showed an ill defined ovoid pink friable mass with a portion of necrotic yellow area. Light microscope showed gyriform or glendular pattern devided by fine fibrovascular stroma. The cells have round vesicular nuclei with prominent nucleoli located in relatively basally and abundant cytoplasm. Multiple electron-dense cytoplasmic zymogen granules in cytoplasm of the enlarged acinar cells on electron microscope can lead the diagnosis. We report the CT and angiographic findings of a case of acinar cell carcinoma in pancreas.

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A case of Multicentric Castleman's Disease: Yong Ho Song, Seon Ho Hwang, Jae Woong Lee, In Soon Kim, You Hern Ahn, Ho Joong Kim, Young Hyeh Ko; J Korean Cancer Assoc. 1995;27(4):696-703.

Abstract PDF: Multicentric Castleman's disease is a systemic lymphoproliferative disorder, characterized by generalized lymphadenopathe, multisystem involvement, disordered immunity and an in- creased incidence of malignant tumors, particularly Kaposis sarcoma and lymphoid neoplasia. The clinical presentation and laboratory features of this syndrome are similar to those of an- other atypical lymphorliferative disorder, angioimmunoblastic lymphadenopathy with dysproteinemia, although this is histologically different from Castleman's disease. A 21-year old male presented ta us with complaints of arthralgia and myalgia of 4 months duration, followed by 2weeks of high fever. Initial physical findings showed small, generalized lymphadenopathies in cervical, axillary and inguinal areas. He developed hepatosplenomegaly and pleuropericardial effusions rapidly. Lymph node biopsy from left inguinal area was consistent with angiofollicular lymph node hyperplasia, plasma cell type.

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