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Volume 28(3); 1996
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Original Articles
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An Immunohistochemical Study of Correlation between Expression of Plasminogen Activator Inhibitor-1 and Lymph Node Metastasis in Gastric Adenocarcinoma
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Yeong Ok Kim, Man Ha Huh
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J Korean Cancer Assoc. 1996;28(3):405-141.
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Abstract
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- Plasminogen activator inhibitor-1 (PAI-1) is inhibitor of plasminogen activator(PA) which is serine protease involving proteolytic degradation of the extracellular matrix and tumor invasion and metastasis. Detailed analysis of the PAI-1 in malignant tissues has not yet been reported. To investigate whether expression of PAI-1 in gaatric adenacarcinoma correlates with lymph node metastasis, immunohistochemical analysis using monoclonal antibody for this antigen was performed in 101 cases of gastric adenocarcinomas. Specific immunostaining was detected in the cytoplasm of the cancer cells and was not detected in stromal cells. Expression of PAI-I was evident in 61% of gastric adenocarcinomas with lymph nade metastasis and 38% without lymph node metastasis (p<0.05) But, the PAI-1 expressian is not related to the number of lymph node metastasis and histopathologic grade. The results support the suggestion that PAI-1 may play a crucial role in metastatic progression of gastric adenocarcinoma and may serve to modulate proteolysis by PA.
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Immunoelectron Microscopic Localization of Transforming Growth Factor Beta1 and Bate2 in Human Gastric Carcinoma Cells
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Young Euy Park
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J Korean Cancer Assoc. 1996;28(3):411-418.
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Abstract
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- Immunohistochemical and immunoelectron microscopic studies were performed using specific monoclonal antibodies to transforming growth factor(TGF)-¥al, ¥a2 to determine their presence and cellular localization in human gastric adenocarinoma cells. Specific immunostaining was clearly detected in the cytoplasm of the neoplastic cells. The TGP-¥al, -¥a2 expression in the gastric adenocarcinoma is closely related to the depth of invasion, the degree of invasiveness and the presence of metastasis. In immuno-electron microscopy by 10nm gold particles, there are TGF¥a1, -¥a2 lacalized predominantly in the cytoplasm of the neoplastic cells. The gold particles were present within the secretory granules. The TGF-¥al, ¥a2 are not present in the cytoplasmic organells such as Golgi apparatus, mitachontria or rough endoplasmic reticulum.
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Interphase Cytogenetic Analysis of Gastric Carcinogenesis using Chromosome in Situ Hybridization
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Sun Young Kim, Ji Yun Bae, Jee Won Seo, Sang Suk Lee
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J Korean Cancer Assoc. 1996;28(3):418-427.
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- Gastric cancer development has been proposed to present a multistep process characterized by dysregulation of proliferation and differentiation and driven by an accumulation of genetic alterations in anatomic field repeatedly exposed to carcinogens. As a first part,of research for gastric carcinogenesis and prevention, we probed 30 early gastric cancers and their adjacent normal tissue including premalignant lesions for numerical chromosome aberrations by nonisotopic, in situ hybridization using chromosome specific centromeric DNA probe for chromosome 17, to visualize the accumulation of genetic alterations during gastric carcinogenesis and to determine the extent of the genetically altered field. The mean chromosome index(CI) increased as the tissue passed from normal adjacent gland(NG) to intestinal metaplasia(IM) to cancer(EGC) (l.06, 1.12, 1.26). Moreover, the frequency of cells with chromosome polysomy (cells with 3 or more chromosome copies) increased as same pattern (4.2%, 9.4%, 20.2%). All cases with EGC, 28/30 cases with IM, 15/30 cases with NG showed significant polysomies(i.e., polysomy frequency > 3% of total populations). As a second part of investigation, 30 cases of gastric adenoma tissue were probe with same centromeric chromosome probes for 5 and 17, to visualize the genetic alteration of isolated benign or premalignant gastric lesion. The mean CI were 1.16 and 1.17, respectively and the frequency of polysomy were 7.6% and 4.0%, respectively. These findings of progressive genetic changes as the the tumor develops support the concept of multistep carcinogenesis and field cancerization. Such genetic parameters could serve as biomarkers of intermediate end points for risk assessment of progression to malignancy or chemoprevention trials.
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The Prognostic Significance of the p53 Protein Expression in Gastric Carcinoma
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Han Il Lee, Young Soo Huh, Wan Sik Yu, Ik Soo Kim
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J Korean Cancer Assoc. 1996;28(3):427-432.
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Abstract
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- p53 expressian in formalin-fixed paraffin-embedded samples of 55 patients with gastric carcinoma, who underwent gastrectomy, was analyzed immunohistochemically with DO-7, a monoclonal antibody. In 21 of 55 tumors (38.2%), nuclear immunoreactivity for the p53 protein was detected. There was no correlation with depth of tumor invasion, lymph node metastasis, distant metastasis, stage of cancer or histologic type. p53 expression was not correlated with prognosis in survival analysis. These results showed that the p53 protein expression can not be used as a prognostic indicator in gastric carcinoma.
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Expression of Proliferating Cell Nuclear Antigen and Epidermal Growth Factor Receptor in Colorectal carcinomas : Relation of Clinical and Patho
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Young Chae Chu, Joon Mee Kim, Young Sik Kim, Young Bae Kim, Tae Sook Hwang
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J Korean Cancer Assoc. 1996;28(3):432-443.
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- To evaluate the prognostic significance of PCNA and EGFR in colorectal carcinoma, the author analysed 66 colorectal carcinomas in paraffin sections immunohistochemically, using the monoclonal antibody PCNA and EGFR and compared with clinicopathological data. The mean PCNA index of colorectal carcinomas was 49.0¡¾10.8%. PCNA index had positive correlation with lymph node metastasis(p<0.001), distant metastasis(p<0.001), modified Dukes' stage(p<0.001), Jass new prognostic classification grouping(p<0.00l), TNM classification(p<0.001) and tumor size over 10.0cm(p<0.05), degree of histologic differentiation(p< 0.01), fibrosis(p<0.05), perineural invasion(p<0.05), lymphatic and vascular invasion(p<0.05). PCNA expression was more pronounced at the infiltrative margins of the tumor and tumor cells within the lymphatic or vascular channels. But there was no relationship between PCNA index and patients age, sex and tumor location, growth pattern, degree of peritumoral lymphocytic infiltration. The positivity of EGFR in colorectal carcinomas was 93.9% and there was an association between staining intensity and the extent of EGFR expression(rs=0.684, p<0.001) and PCNA index(rs=0.451 & 0.432, p<0.001). There was an association between staining intensity and the extent of EGFR expression and modified Duke's stage(p<0.001), Jass grouping(p<0.001), TNM classification(p<0.001), lymph node metastasis(p<0.001), fibrosis(<0.05), lymphocytic infiltration(p<0.05), lymphatics and vascular invasion(p< 0.01). These results suggest PCNA index and EGFR expression may be a useful prognostic factors in colorectal carcinomas. Knowledge af the percentage of PCNA-positive cells could be especially helpful in deciding to treat patients with adjuvant chemotherapy.
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Transforming growth Factor - beta ( TGF-β ) as a Mediator of Tamoxifen and Retinoic Acid in Breast Carcer
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Hy Do Lee, Dong Sup Yoon, Chul Woon Jung, Ja Yun Koo
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J Korean Cancer Assoc. 1996;28(3):443-451.
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- TGF-¥a is multifunctional regulatory homodimeric polypeptides and reaulate cell differentiation, cell growth, cell function and is the most potent growth-inhibitory polypeptides known for a wide variety of cell types including most normal and transformed epithelial, endothelial, fibroblast, lymphoid and hematopoietic cells. The production of TGF-¥a by the estrogen receptor-positive cell line MCF-7 has been reported to be most affected by antiestrogens, and Tamoxifen caused a 5-fold increase in production of TGF-¥a by MCF-7 cells and its regulation of TGF-¥a production was thought to be posttranscriptional. Recent work has shown that the proliferation of both mouse and human keratinacytes was potentially and reversibly inhibited by TGF-¥a, and that retinoic acid induced TGF-¥a1 in cultured keratinocytes and mouse epidermis. These results suggest that the regulation of TGF-¥a2, expression by tamoxifen and retinoic acid may have a important role in control of breast cancer cell growth. To obtain better understanding of how tamoxifen and retinoic acid could regulate growth of breast cancer cells, we carried out this experimental study. Using phenol red-free medium, we cultured MCF-7 cells and then treated with various dosage of tamoxifen, retinoic acid and tamoxifen with retinoic acid, and then observed MCF-7 cell growth and the production of TGF-¥a. The growth of MCF-7 cell was markedly inhibited by tamoxifen, and synergistic inhibitory effect was discovered when retinoic acid was supplemented with tamoxifen. Both tamoxifen and retinoic acid increased the secretion of TGF-¥a1, & TGF-¥a2, especially TGF-¥a2. The mRNA induction of TGF-¥a2 was increased by treatment of retinoic acid and it was more increased by treatment of retinoic acid with tamoxifen. As these results, we concluded that Tamoxifen and retinoic acid increased the production of the TGF-¥a2 retinoic acid may be used as second postoperative adjuvant therapeutic agent of breast cancer.
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Expression of NM23 Protein in Breast Cancer - An immunohistochemical study -
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Soo Jung Lee, Jun Duk Suh, Ki Young Kim, Min Chul Chim, Koing Bo Kwun, Dong Sug Kim
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J Korean Cancer Assoc. 1996;28(3):451-461.
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- Expression of a recently identified nm23 gene has been previously proposed to be inversely correlated to tumor metastatic potential It was proposed that nm23 may function as a suppressor gene for tumor metastasis. It has recently been found that the sequence of nm23 and NDP-Kinase(NDP-K) is identical. We studied l42 cases of primary breast carcinoma for the expression of nm23 protein using an immunohistochemical method, and compared these results with other known prognostic factors of the breast carcinoma. The nm23 protein was stained in the cytosol and/or the perinucleus of carcinoma cells in 130 cases(91.5%). Among the positive cases, 67cases were stained to lower density while 63 cases were stained to higher density. There were no significant correlation between nm23 protein and other parameters such as tumor size, axillary lymph node metastasis, histologic parameters, hormone receptor, p53, c-erbB-2, and EGFR. Although expression of nm23 was positively associated with longer disease free survival (p<0.05) but not with overall survival. These study showed that nm23 expression in human breast cancer may be one of the prognostic factors, but further studies using antibodies specific for NDP-K/nm23 subtypes are clearly indicated.
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The Effect of Pentosan Polysulfate and Androgen on Angiogenesis in 9 , 10-Dimethyl-1 , 2-benzanthracene Induced Rat Mammary Carcinoma
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Chae Kyung Moon, Dong Won Kim, So Yeung Jin, Dong Wha Lee
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J Korean Cancer Assoc. 1996;28(3):461-472.
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- Angiogenesis is critical for progressive tumor growth and metastasis. Tumors progress from a prevascular stage to a vascular stage and the vascularized stage permits metastasis. Regulatory mechanisms of the angiogenic process are known to be directly and indirectly related to various angiogenic factors. Recently angiogenesis became an appealing therapeutic modality for the treatment of human malignancies, especially breast cancer. However such an approach has remained little more than good theory. And the clinical field of antiangiogenic therapy stays in its infancy. To evaluate a possibility of antiangiogenic treatment on breast cancer, the author performed an experiment to investigate antiangiogenic activity of pentosan polysulfate(PPS) and medroxyprogesterone acetate(MPA) on 9,10-dimethyl-1,2-benianthracene(DMBA) induced mammary tumors of female Sprague-Dawley rats. The angiogenic and antiangiogenic activities were observed by response rate of the tumor volume, histologic grading and changes, and microvessel densities of the tumors on immunoperoxidase staining for factor VIII-related antigen. The results are followings: 1) Induction rate of mammary tumor after DMBA treatment was 80.1% and about 95% of these tumors were adenocarcinoma. 2) Response rate of mammary carcinoma to MPA and PPS treatment was 45.1% and 40.0% , respectively, and is statistically significant compared with the test control group(p<0. 05). 3) Necrosis was more marked and frequent in tumors of the PPS group than test control group and the histologic grade was lower in the PPS and MPA group than the test control. 4) Microvessel densities of the tumors were significantly lower in the PPS and MPA groups(p<0.05) than the test contral, but there was no significant difference between these two groups(p>0.05). 5) The difference of microvessel density according to response rate tended to be lower in partial response group than in progressive disease group of the test control and PPS groups. In summary, it is concluded that PPS and MPA have antitumor effect on chemically induced rat mammery carcinoma and the antitumor effect of PPS and MPA is related to antiangiogenesis.
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Radioimmunotherapy for Lung Metastasis of MMTV-induced Breast Cancer in Mice with 131I-labeled Monoclonal Antibody
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Sang Kyun Sohn, Jae Tae Lee, Chang Woon Choi, Tibor Bakacs, M . Belen Moreno, Byeong Cheol Ahn, Kyu Bo Lee, David Segal, Chang H . Paik
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J Korean Cancer Assoc. 1996;28(3):472-483.
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- Radiolabeled monoclonal antibodies appear to be gaining a role in the management of cancer by means of imaging methods to detect sites of increased radioactivity, and several products have been developed and tested clinically. In the area of radioimmunotherapy, the radiolabeled monoclonal antibodies have shown the potentials in the treatment of the microtumors and metastases due to its inherited benefit from bystander effect of the ionizing radiation delivered with radioimmunoconjugates. We have evaluated the antitumor effects of I-131 labeled P2AE12 antibody, prepared against glycopratein of gp52 MMTV-induced murine mammary tumor cell, in allogeneic model of pulmonary metastatic cancer. The BALB/c normal mice were injected intravenously with 5 x 10(5) murine breast cancer cells and pulmonary metastases were acauired in all mice. Three days and ten days after tumor cell injection, each set of 250uCi of I-131 labeled antibody was injected in 15-20 mice for one or two treatment group. Survival of treatment group was compared with that of control group. One-treatment resulted in prolonged median survival of mice bearing metastases from 14(range: 13-16 days) to 16 days(range: 1422days), and two-treatments to 22(range: 20 to more than 40 days) days. Treatment with I-131 labeled P2AE12, antibody resulted in marked reduction of tumor burden in lung sections taken on days 7 and 14 days. Our results showed that radiolabeled monoclonal antibody can inhibit the growth of allogeneic solid tumor metastases in mice. Although it did not cure these kinds of aggressive metastatic tumors, these findings encourage the further evaluation of the radioimmunotherapy in pulmonary metastases with different schemes to enhance tumor uptake of radiolabeled antibody, as well as lessen the uptake in normal tissue.
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The Treatment of Malignant Bronchial Obstruction by Laser Photoablation
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Suk Young Park, Wan Wuk Kim
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J Korean Cancer Assoc. 1996;28(3):483-490.
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- Background
Bronchial obstruction by advanced lung cancer is troublesome. Radiation therapy has been the choice of treatment, but it may take the long time until relieving obstruction and cause severe complications. To evaluate the clinical effect and complication of laser photoablation, we performed photoablation with Nd-YAG laser in the patients with malignant bronchial obstruction. Methods: Twenty five patients with advanced lung cancer(24)and bronchial cystic carcinoma(l) were treated with laser photoablation for the symptomatic palliation of life- threatening bronchial obstruction from 1990 to 1994, in Daejeon St Mary's Hospital of Catholic University Medical Colledge. Results: The degree of bronchial obstruction and the performance status scales were markedly improved within a few days after laser photoablation. The degree of bronchial obstruction was reduced in twenty three cases(92%) and the Performance Status by Karnofsky Scales was improved from less than 30 to more than 50 in twenty one cases(84 %) after laser photoablation. Threre was no serious complication and no procedure-related mortality. Complications were as follows; fever(28%) and mild hemoptysis(16%). Conclusion: Laser photoablation is an effective therapeutic modality for the palliation of bronchial obstruction caused by advanced lung cancer. The procedure is very tolerable and safe without serious complication.
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Expression of Keratin Subrypes in Lung Tumprs
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Keun Hong Kee, Chan Guk Park, Cheol Hee Choi
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J Korean Cancer Assoc. 1996;28(3):490-502.
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- Keratin is a major class of epithelial intermediate filaments, and comprises a group at least 20 different multigene derived proteins. It is expressed in different epithelia with specific combinations. Polyclonal and monoclonal antibodies to cytokeratin(CK) polypeptides were used to study the expression in normal, squamous metaplasia, reserve cell hyperplasia, and neoplastic epithelium of the respiratory tract. All cases were performed of immunohistochemical stain for panel of monoclonal cytokerain antibodies. Also, some cases were examined by electron and immunoelectron microscopy. The squamous papillomas were positive for CK 1, 5/6, 8, 10 and 17. Dysplastic cells were positive for CK 1, 13, 14, and 19. Well differentaited squamous cell carcinomas were reactive for CK 1, 5/6, 13, 14 and 17. Poorly differentiated squamous cell carcinomas were reactive for CK 5/6, 8, 10 and 19. Small cell carcinomas were negative for all keratin subtypes. Adenocarcinomas are reactive for CK 7, 8, 18 and 19. CK 20 is exceptionally negative in all cases. Immunoelectron microscopic examination shows localized gold particles in intermediate filaments and tonofilaments of normal or tumor cells. In conclusion, keratin subtypes of well differentiated squamous cell carcinoma is similar to those of metaplastic cells of the bronchial epithelium and dysplastic cells, while keratin subtypes of poorly differentiated squamous cell carcinoma resembles those of hyperplastic reserve cells and squamous papilloma. It is thought that the application af cykokeratin panel can indicate the degree of differentiation of tumors and distinguish the main subtypes of lung cancer. In addition,immunoelectron microscopic examination is helpful to lo- calization of keratin filaments and diagnosis of epithelial tumors.
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A Study on the Loss of Heterozygosity of the Retinoblastoma Gene in Primary Uterine Cervical Carcinomas
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Chun Geun Lee, Young Ju Choi, Hong Ki Min, Joo Ho Kim, Youl Hee Cho, Jin Woo Kim, Jae Hoon Kim, Tae Eung Kim, Jae Keun Jung, Sung Eun Namkoong
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J Korean Cancer Assoc. 1996;28(3):502-512.
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- Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancers. In order to detect loss of heterozygosity(LOH) within one of the well-known tumor suppressor gene, Rb(retinoblastoma), in primary uterine cervical cancers, we analysed four polymorphic intronic sites of Rb locus using polymerase chain reaction(PCR) in 55 primary cervical cancer tissues. The estimated heterozygote frequencies of intronl/BamHI, intronl7/XbaI, intron25/DraI, and intron 20 variable number of tandem repeat(VNTR) regions were 49%, 49%, 42%, and 80%, respectively. The observed frequencies of tumors with LOH at each locus were 21%(5 /24), 17%(5/29), 20%(5/20) and 44%(7/44) for intronl/BamHI, intronl7/XbaI, intron25/DraI and intron 20 VNTR polymorphic loci, respectively. The overall frequency of cervical cancer with at least one LOH at the Rb locus in this study was 14%(7/49), indicating that LOH at the Rb locus was not necessarily associated with cervical carcinogenesis. All the tumors showing LOH at the Rb locus were histologically moderatelv to poorly differentiated types and most of them(5 of the 7, 71%) were over FIGO stage II. These results suggest that the tumors with LOH at this locus may represent the general genomic instability which will contribute to the tumor progression and LOH of this gene may be used as one of the prognostic factors in cervical cancer in the future.
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Alterations in DNA Cleavage Site of Topoisomerase 2 by Benzo(a)pyrene , m-AMSA , Ellipticine and Doxorubicin in Human c-myc Protooncogene
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Sang Wook Lee, In Cheol Jeong, Moo Youn Cho
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J Korean Cancer Assoc. 1996;28(3):520-533.
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- The nuclear enzyme DNA topoisomerase II, involving in DNA replication and transcription, mediates DNA scission in cells exposed to certain classes of intercalating agents, and is trapped as a covalent protein-DNA complex. In a previous study, we have found that benzo(a)pyrene(BP) and it's metabolites specifically bind to the DNA topoisomerase II fraction of mouse fibroblast C3H/10Tl/2 cell cultures. The enzyme was predicted to be a primary target of BP, causing malignancy. We therefore investigated in the present study changes in DNA cleavage by various concentrations of BP bound to DNA topoisomerase II in the human c-myc protooncogene. At the same time, the effects of m-AMSA(amsacrine), ellipticine and doxorubicin were also investigated. DNA topoisomerase II was purified by glycerol gradient centrifugation from mouse leukemia L1210 cells which easily form pro tein-DNA cross linkage. In the experiments of agarose gel electrophoresis which analyzed genomic changes in the human c-myc DNA, the pBR322 DNA was completely reversed from a supercoiled to a relaxed form in the presence of 160ng of purified DNA topoisamerase II. In BP-treated Hind III/Xba I cutting c-myc DNA, DNA cleavage was most apparently increased at 1.7 kb site, the effect being particularly pronounced with 0.1 ¥i M BP. Genomic changes by drug-induced DNA topoisomerase II in the labelled with P32 to restricted c-myc DNA were enhanced predominantly in the cleavage sites of P2 promoter region with m-AMSA, ellipticine and doxorubicin, and in the upstream of exon 1 with BP. In in vivo experiments, in which the effect of BP exposure of in human lymphoblast NC- 37 cells was tested, there was no change in c-myc RNA expression by 0.25 ¥ig/ml of BP. However, the c-myc RNA expression increased significantly with BP of 2.5 ¥ig/mL A simi lar increase in RNA expression was observed in Burkitt lymphoma cells. These resu1ts indicate that an increase of DNA cleavage or increased cleavage at specific sites induce gene expression of abnormal pattern.
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CA Repeat Polymorphism at the D5S346 Locus Tightly Linked to Adenomatous Polyposis Coli ( APC ) Gene in Korean Population
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Hye Jung Han, Yong Jin Won, Kyu Joo Park, Jae Gahb Park
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J Korean Cancer Assoc. 1996;28(3):533-544.
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- A subclass of human tandemly repeated DNA contains very short simple sequence repeats such as (dC-dA). (dG-dT), designated as CA repeats or (CA). It is now recognized that there are 50,000-100,000 interspaced (CA), blocks in the human genome. The function of these repeat sequences remains obscure, but since (CA). exhibit high degree of length polymorphisms and Mendelian inheritance, they can be extremely useful for genetic diagnosis of hereditary diseases. In this paper, we have examined the CA repeat polymorphism at the D5S346 locus, which is located 30~70kb downstream to the APC (adenomatous polyposis coli) gene responsible for development of familial adenomatous polyposis, in 55 unrelated Koreans. We were able to identify 11 different alleles ranging from 114 to 138 base pairs(bp) in size. The observed heterozygosity was 0.60. Using this information, we could successfully make presymptomatic diagnosis of all the at-risk individuals in 2 Korean familial adenomatous polyposis(FAP) families. Our result indicates that higly polymorphic dinucleotide (CA)-repeat marker D5S346 can serve as an important tool for presymptomatic diagnosis of Korean FAP families.
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Germline Mutations of VHL gene in Korean von Hippel - Lindau Disease Patients
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Ki Hyuk Shin, Kyu Joo Park, Soo Woong Kim, Sang Hoon Lee, Sang Eun Lee, Hee Won Jung, Hyun Jip Kim, Jae Gahb Park
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J Korean Cancer Assoc. 1996;28(3):544-555.
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- Von Hippel-Lindau(VHL) disease is an autosomal dominant disease characterized by development of different tumors in diverse organs, including hemangioblastoma of the central nervous system, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. The gene responsible for this disease, the VHL gene, was recently cloned and germline mutations of this gene identified in patients with VHL. Using polymerase chain reaction(PCR)-single strand conformation polymorphism(SSCP) analysis followed by DNA sequencing, we were able to identify germline mutations of the VHL gene in two unrelated Korean patients exhibiting typical clinical features of the VHL disease. The mutations identified were 2 base pair deletion at codon l79 in one patient, and a missense mutation at codon 190 in the other. Identification of the germline mutation in VHL gene aids in the accurate presymptomatic diagnosis of the at-risk family members of these patients.
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Effect of Combination Chemotherapy with Recombinant Interferon Alpha-2a for Palliative Therapy of metastatic Renal Cell Carcinoma
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Jae Cheon Ahn, Seong Choi, Hyun Yul Rhew
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J Korean Cancer Assoc. 1996;28(3):555-562.
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- The prognosis for metastatic renal cell carcinoma is poor, and also there is no effective treatment for this cancer. Recombinant interferon alpha-2a displays subadditive. additive, and synergic effects when used with a number of cytotoxic agents is vitro and in vivo tumor models. A total of 3l petients with metastatic renal cell carcinoma was recieved recombinant interferon alpha-2a, vinblastine, CCNU and medroxyprogesterone acetate between March 1988 and December 1993. Their mean age was 53.8 years (range; 14 - 78 years).The male to female ratio was 2.1:1. Histologically, clear cell type was dominant (83.8%).Lung metastasis only was in 13 cases(41.9%) and multiple metastasis was in 18cases.Using the deKerion criteria for response, the response rate was 29%(9 cases). The 1,2,5 year survival rates of all the patients were 48%, 18%, 18% respectively, 100%, 60%, 60% for the responder group and 24%, 8%, 0% for the nonresponder (p=0.004).In combination chemothetherapy with recombinant interferon alpha-2a, the Karnofsky performance index was the most significant prognostic factor(p=0.015). Age, sex, metastatic sites, cell type and disease free interval had no significance(p>0.05).The most common side effects were constitutional symptoms(93.5%).Hematologic toxicity(41.9%),G-I toxicity(41.9%) and hepatic toxicity(6%) occured. In conclusions, combination chemotherapy with recombinant interferon alpha-2a raised remssion and survival rates and can be on effective palliative therapy in patients with metastatic renal cell carcinoma.
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A Prospective Randomized Study Comparing the Efficacy of Tropisetron Versus Metoclopramide / Dexamethasone / Diazepam (
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Ki Bok Park, Dong Hoon Jeong, Jong Hoon Kim, Byoung Kee Kim, Sang Yoong Park, Eui Don Lee, Kyung Hee Lee
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J Korean Cancer Assoc. 1996;28(3):562-573.
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- Background
Chemotherapy-induced emesis is one of the most disturbing side effects in the cancer chemotherapy. Despite a number of significant advances over the past decade, prevention and treatment of chemotherapy induced emesis remain formidable problems, particularly with cisplatin based regimens. In the prior reports, tropisetron(Navoban, Sandoz Pharma. Ltd., Basel, Switzerland), a 5-HT3-receptor antagonist, was effective in the control of cisplatin induced emesis. In this study, we compared effectiveness of tropisetron (TRP) with metoclopramide/dexamethasone /diazepam(MDD) in the prevention of emetic episodes in patients receiving cisplatin-based combination chemotherapy. Methods: Sixty-three patients with cervical carcinoma receiving 60 mg/§³ of cisplatin (day 1) and 1000mg/§³ of 5-FU(day 1~5) were randomized to two arms(arm I: tropisetron; n=32, arm II: MDD; n=31). In TRP group, tropisetron(5 mg) was given intravenously(i.v.) l5 min before cisplatin on day 1, and per orally(p.o.). 30 min before breakfast from day 2 to 6. In MDD group, metoclopramide(l mg/kg/time, 2 times/day), dexamethasone(20mg) and diazepam(5 mg) were given intravenously before cisplatin infusion on day 1, and from day 2 to 6, metoclopramide(l0 mg) was given p.o, every 6 hours, and dexamethasone was given p.o . every 12 hours at a dose of 8mg on day 2~3 and at a dose of 4mg on day 4~6. Sixty patients were evaluable and 3 patients(arm I, 2 patients; arm II, 1 patient) were excluded from the analysis due to their refusal during study due to emesis. Results: In TRP group, during first 24 hours(acute emesis), 83.3%(25/30) of patients had fewer than three emetic episodes and 63.3%(19/30) had no emetic episodes. These results were similar to those of MDD group; 90.0%(27/30) and 63.3%(l9/30), respectively. But from that time to day 6, in TRP group, anly 53.3%(16/30) of patients had less than three emetic episodes and 20.0%(6/30) had no emetic episode. These were significantly less than those of MDD group; 86.7%(26/30) and 50.0%(15/30)(p<0.001). The mean nausea ratings per visual analogue scale between two groups on day 1 were similar; 49.0¡¾7.5(mean¡¾S.E.M) for TRP group and 43.3¡¾7.1 for MDD group. But from day 2 to day 5, the mean nausea ratings for MDD group were significantly less than those for TRP group(p<0.05). We could observe various side effects such as gastrointestinal symptoms and sedation in MDD group but no side effects except mild headache(10.0%) were observed in TRP group. Extrapyramidal symptom was not observed in both groups. Conclusion: These results suggest that TRP was as effective as MDD in controlling the acute emesis but less effective in controlling the delayed emesis induced by cisplatin-based chemotherapy. Although antiemetic effect of tropisetron was not more excellent than that of MDD regimens, it seems to be a clinically efficacious drug due to simplicity of administration and less side effects.
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Effect of One - day ( G1 ) and Two - day ( G2 ) Schedule of Intravenous Granisetron on Prevention of nausea and Vomiting and Qualit Of Life during Cisplatin - Containin
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Woo Sung Min, Han Lim Moon, Jin Hyoung Kang, Jong Youl Jin, Choon Choo Kim, Dong Jip Kim, Seong Ja Choo, Kyung Shim Kang, Jae Boon Ryu
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J Korean Cancer Assoc. 1996;28(3):573-582.
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- Background
Nausea/vomiting is one of the most important item on deterioration of quality of life(QOL) in patients with cisplatin-containing chematherapy and may ultimately result in delay or refusal of the next chemotherapy. Although 5-hydroxy tryptamine 3(5-HT3) antagonist, ondansetron successfully controls cisplatin-induced nausea/vomiting during the first 24 hours, it fails to control nausea/vomiting on the following 24 hours in many patients. Authors performed this study to compare the effect of one-day and two-day schedule of intravenous granisetron on prevention of cisplatin-induced nausea and vomiting and QOL. Method: The antiemtic effect and QOL between one-day and two-day schedule of 3 mg/day of intravenous granisetron in cycle 1 and cycle 2 of cisplatin-based chemotherapy were compared. Frequency and severity of nausea/vomiting, QOL, oral intake and side effects were evaluated daily since day 0 to day 7 of chemotherapy. Results: Thirty eight patients were enrolled and 37 patients(31 male, 6 female, median age 60 with range of 42~74) were evaluable. The range of cisplatin were 50~l00mg/§³ and one or two of other chemotherapeutic agents such as 5FU, VP16, ifosfamide and mitomycin were combined. We evaluated the number of vomiting and QOL index with 10 items including nausea/vomiting and anorexia from day 0 to day 7 of chemotherapy. Twelve of 37 could not receive the G2 because of discontinuation of chemotherapy or patient's refusal of granisetron any more and eventually 25 had both Gl and G2. Time to first vomiting, control of vomiting and the amount of oral intake on day 1, day 2 and the worst day and side effects were not different between Gl and G2. QOL on day 2(G1; 56.2¡¾16.2 vs G2; 68.4¡¾20.3)(p<0.05) and change of QOL since day 1 to day 2 of cispltin(Gl; 16.3+2.1 vs G2 0.07+0.6)(p<0.01) were significantly different. Conclusion: Although the additiional intravenous granisetron on day 2 of cisplatin-based chemotherapy did not control nausea/vomiting more successfully, it improved QOL on the second day and the change of QOL from day 1 to day 2.
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A Comparison of the Acute Antiemetic Effect of Granisetron with Combination of Metoclopramide , Dexamethasone and Lorazepam in Patients Receiving High
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Won Yong Shin, Seong Gyu Park, Jin Woo Jeon, Jong Ho Won, Seung Ho Baik, Dae Sik Hong, Dae Sik Hong, Hee Sook Park
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J Korean Cancer Assoc. 1996;28(3):582-589.
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Abstract
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- Granisetron, a 5-hydroxytryptamine3(5-HT3) receptor antagonist, is effective antiemetic agent in the control of cisplatin-induced emesis. We compared the efficacy and safety of granisetron with those of intravenous high-dose metoclopramide(1.5 mg/kg, four times) plus dexamethasone(10 mg i.v.) and lorazepam(2 mg i.v.)(MDL therapy) to control the acute emesis induced by high-dose cisplatin(>60mg/§³) treatment. Granisetron was injected in dose of 3 mg intravenously as recommended schedule for the prophylaxis of acute cisplatin-induced emesis. Granisetron was effective as MDL therapy for controlling of acute emesis. Of 25 granisetron-treated patients, 18(72%) were complete or major responders compared with 19/25(76%) patients who recieved the MDL therapy on first day of chemotherapy(P> 0.05). Also, in controlling of nausea, granisetron results were similar to MDL therapy. Side effects attributable to MDL group were sedation(60%)(P<0.01) and dizziness(20%)(P<0.05). In contrast to, headache(20%) of the granisetron group was higher than that of MDL group(P<0.05). Granisetron was effective as MDL therapy for controlling of the acute em esis and nausea induced by cisplatin. But, granisetron was more feasible and safer than MDL therapy.
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An Early Diagnosis of Cancer by the Detection of Parameter Changes in Dynamical Systems
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Kwon Soon Lee
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J Korean Cancer Assoc. 1996;28(3):589-597.
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Abstract
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- The researcher proposed a mathematical model of the interaction between tumor cells and the immune system to obtain a better understanding of body immune processes. It provides the systematical analysis of cancer and immune system using system and control theory in engineering. An early detection of cancer is very important for the complete cure of cancer. Therefore, it is considered a diagnosis of cancer via the detection of an abrupt change from the healthy state to the cancerous state. The statistical testing is proposed to implement a parameter change algorithm. The detection algorithm studied in this research is based on sequential hypotheses testing in a so-called local asymptotic framework. Here a simple numerical example is provided to highlight some of the concepts and to provide a basis for further investigation. Despite its simplicity this research may have practical application in clinical oncology.
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A Case of Chronic Neutrophilic Leukemia
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Bong Kee Cho, Bum Chan Kweon, Han Kyung Lee, Keun Ha Nam, Seog Jun Kim, Choong Ki Lee, Sae Yoon Chung
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J Korean Cancer Assoc. 1996;28(3):597-604.
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Abstract
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- Chronic neutrophilic leukemia is a very rare myeloproliferative disorder. It is characterized by severe sustained neutrophilic leukocytosis, hepatosplenomegaly, elevated leukocyte alkaline phosphatase score, elevated serum vitamin B12,, negative Philadelphia chromosome and the absence of fever or an underlying infection or disease capable of provoking a leukemoid reaction. We have experienced a typical case of chronic neutrophilic leukemia in 75 years old man who complained a huge intramuscular hematoma due to bleeding tendency despite normal finding of coagulation test. Philadelphia chromosome was negative with normal karyotype and he showed marked neutrophilic leukocytosis with 92.2% segmented neutrophil, elevated leukocyte alkaline phosphatase score, and reduced GM-CFU(granulocyte macrophage-colony forming unit).
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A Case of Bladder Rhabdomyosaroma in Child
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Hee Jong Jeung, Sam Ryong Lee, Kwang Sung Park, Soo Bang Ryu, Hoon Kook, Tai Ju Hwang
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J Korean Cancer Assoc. 1996;28(3):604-611.
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Abstract
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- Embryonal rhabdomyosarcoma arises from the embryonal mesenchyme that differentiates into striated skeletal muscle, and about 15 to 20% of rhabdomyosarcomas are genitourinary in origin. Rhabdomyosarcoma of urogenital origin occurs at 2 age peaks: one in children between 2 and 6 year old and the other during adolescence between ages 15 and 19 year old. We report a case of embryonal rhabdomyosarcoma of the bladder in a 3-year-old male. He presented dysuria with straining and dribbling, and diagnosis was made by cystoscopy and biopsy. Since partial cystectomy was performed, and he has being received continuous Pulse VAC chemotherapy with radiotherapy.
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