A canine lung cancer model
2
44 These results indicate the existence of..oat-SCLC-leukemia common tumor-asso- ciated antigens. The Mo-Abs are useful in the diagnosis of oat-SCLC or acute leukemia. Significance of Carbohydrate Antigen 19.9 (CA19-9) as a Tumor Marker for Lung Carcinomas. Kurata, M., Takeda, A., Tachibana . H., Muromoto, H., Chin, K., Tanaka, K., Ka- gioka, H., Kubo**, K. **Div. Thoracic Surgery, **Div. Internal Medicine Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan. CA19-9, a new tumor marker which has been defined by a monoclonal antibody, was assayed in 83 cases of pulmonary dis- ease, including 58 cases of lung cancer, and its significance as a tumor marker for lung cancer was studied in compari- son with the values for Carcinoembyonic Antigen (CEA) assayed at the same time. CA19-9 was assayed using a Centocor CA19-9 RIA kit and a value of 38 or more was considered positive. CEA was assayed by means of the sandwich method and a value of 2.6 or more, or 5.1 or more, was considered positive. Lung Cancer Benign Pulmonary (58 cases) Diseases Including COLD (25 cases) CEA> 2.6 35(60%) 9 (36%) CEA> 5.1 24(41%) 1 (4%) CAI~-9>38 20(35%) 3 (12%) CA19-9 was found to yield false posi- tives less often than CEA. CA19-9 tested positive in lung cancer cases as follows: adenocarcinoma 41% (ll/27~cases), squa- mous cell carcinoma 21% (3/14 cases), lar- ge cell carcinoma 30% (3/10 cases), and small cell carcinoma 43% (3/7 cases). CA19-9 value for the tumors was general- ly higher than for the blood. There were also cases in which CA19-9 tested high (positive) for the tumor but normal (negative) for the blood. Tissue Polypeptide Antigen (TPA), Carci- noembryonic Antigen (CEA), and CA-50: A Useful Tumour Marker Combination for Non- Small Cell Lung CarcSnomas (NSCL~). Nilsson~ S., Brodin ~, O., Sil~n ~, A, Lindholm , L. i. Department of Oncology, Akademiska Sjukhuset, University of Upp- sala, S.751 85 Uppsala. 2. Sangtec Medi- cal, Box 200 45, S-161 20 Bromma. 3. Department of Medical Microbiology, Sahl- grenska Sjukhuet, University of G6teborg, S-413 45 G6teborg, Sweden. There is a need for better tumour mar- kers in the management of NSCLC. In this study TPA, a protein related to cytokera- tins, CEA, and Ca-50, a tumour associated ganglioside antigen, were investigated. Sera from 51 patients with NSCLC were drawn prior to therapy and stored at -80°C until analysis. The tumour mar- kers were quantified by the use of radio immuno- assays. The upper normal limits used were 90U/I, 5 ug/l, and 17 U/l for TPA, CEA, and Ca-50, respec- tively. The mean TPA value for 31 patients with limited disease (L~was 107 U/1, whereas that of 9 patients with extensive disease (ED) was 216 U/l. The difference between the two groups was signifi- cant according to Mann-Whitney's U-test. About 70% of the patients had elevated levels with re- spect to TPA. Among the patients in the TPA nega- tive group, about every second showed elevated CEA levels, and in the TPA-CEA negative group, almost every third patient showed elevated Ca-50 levels. Consequently, close to 80% of the patients with NSCLC had elevated serum levels with respect to at least one of the three antigens prior to therapy. The antigens seemed to follow the course of the disease fairly well. Thus this tumour mar- ker combination seems to be of potential value in the management of the disease. ~bnoclonal Antibodies to Non-Small Cell Lung Car- cinomas. Namikawa, S., Rao, U., Chen, S., Pollard, C., Takita, H., Bankert, R.B. Roswell Park Memorial Institute, Buffalo, New York. Three different monoclonal antibodies, 5C7, 5E8, and IF10 generated against primary adenocarcinoma, squamous cell carcinoma and large cell carcinoma of lung, respectively were assayed on fresh frozen tissue obtained from 36 lung cancers and 40 con- trol specimens employing double antibody immuno- peroxidase technique. Intensity of positive reac- tion and its pattern of distribution was roughly quantitated and also simultaneously compared to the pattern of distribution of keratins AEland AE 3 (Hybritech) and antikeratin and CEA (D/IKO) and preliminary findings are reported. Cross sections occurred but antibodies did not react with sarco- mas, melanoma and lymphomas. Antibody 5C7 reacted strongly with well differentiated adenocarcinoma and large cell carcinoma and with less intensity with squamous cell carcinoma. Intensity of stain- ing appeared to be proportional to the differen- tiation of the neoplasm. 5E8 also reacted with all cell types of lung cancer, but higher scores were obtained with squamous cell carcinoma. On the con- trary, about 60% of well differentiated adenocar- cinoma were negative, iF10 reactions were stron- gest with the poorly differentiated adenocarci- noma/large cell group. No significant differences in staining reactions of primary or metastatic lung carcinoma was found. Interesting findings were focal areas of positivity with Caltitonin (Histotech) in four cases of squamous cell carci- noma of lung and ~HCG in a single case of large cell carcinoma. Correlation of above findings with clinical behavior of the tumors will be presented. A Canine Lung Cancer ~bdel. Benfield, J., Harmnond, W., DeCaro, L., Paladugu, R. Pak, H., Teplitz, R.. City of Hope National Medical
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Transcript of A canine lung cancer model
44
These results indicate the existence of..oat-SCLC-leukemia common tumor-asso- ciated antigens. The Mo-Abs are useful
in the diagnosis of oat-SCLC or acute leukemia.
Significance of Carbohydrate Antigen 19.9 (CA19-9) as a Tumor Marker for Lung
Carcinomas. Kurata, M., Takeda, A., Tachibana . H., Muromoto, H., Chin, K., Tanaka, K., Ka- gioka, H., Kubo**, K. **Div. Thoracic Surgery, **Div. Internal Medicine Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan.
CA19-9, a new tumor marker which has been defined by a monoclonal antibody, was assayed in 83 cases of pulmonary dis- ease, including 58 cases of lung cancer, and its significance as a tumor marker for lung cancer was studied in compari- son with the values for Carcinoembyonic Antigen (CEA) assayed at the same time.
CA19-9 was assayed using a Centocor CA19-9 RIA kit and a value of 38 or more was considered positive. CEA was assayed by means of the sandwich method and a value of 2.6 or more, or 5.1 or more, was considered positive.
Lung Cancer Benign Pulmonary (58 cases) Diseases Including
COLD (25 cases) CEA> 2.6 35(60%) 9 (36%) CEA> 5.1 24(41%) 1 (4%) CAI~-9>38 20(35%) 3 (12%)
CA19-9 was found to yield false posi- tives less often than CEA. CA19-9 tested positive in lung cancer cases as follows: adenocarcinoma 41% (ll/27~cases), squa- mous cell carcinoma 21% (3/14 cases), lar- ge cell carcinoma 30% (3/10 cases), and small cell carcinoma 43% (3/7 cases). CA19-9 value for the tumors was general- ly higher than for the blood. There were also cases in which CA19-9 tested high (positive) for the tumor but normal (negative) for the blood.
Tissue Polypeptide Antigen (TPA), Carci- noembryonic Antigen (CEA), and CA-50: A Useful Tumour Marker Combination for Non- Small Cell Lung CarcSnomas (NSCL~). Nilsson~ S., Brodin ~, O., Sil~n ~, A, Lindholm , L. i. Department of Oncology, Akademiska Sjukhuset, University of Upp- sala, S.751 85 Uppsala. 2. Sangtec Medi- cal, Box 200 45, S-161 20 Bromma. 3. Department of Medical Microbiology, Sahl- grenska Sjukhuet, University of G6teborg, S-413 45 G6teborg, Sweden.
There is a need for better tumour mar- kers in the management of NSCLC. In this study TPA, a protein related to cytokera-
tins, CEA, and Ca-50, a tumour associated
ganglioside antigen, were investigated. Sera from
51 patients with NSCLC were drawn prior to therapy and stored at -80°C until analysis. The tumour mar- kers were quantified by the use of radio immuno- assays. The upper normal limits used were 90U/I, 5 ug/l, and 17 U/l for TPA, CEA, and Ca-50, respec- tively. The mean TPA value for 31 patients with limited disease (L~was 107 U/1, whereas that of 9 patients with extensive disease (ED) was 216 U/l. The difference between the two groups was signifi- cant according to Mann-Whitney's U-test. About 70% of the patients had elevated levels with re- spect to TPA. Among the patients in the TPA nega- tive group, about every second showed elevated CEA levels, and in the TPA-CEA negative group, almost every third patient showed elevated Ca-50 levels. Consequently, close to 80% of the patients with NSCLC had elevated serum levels with respect to at least one of the three antigens prior to therapy. The antigens seemed to follow the course of the disease fairly well. Thus this tumour mar- ker combination seems to be of potential value in the management of the disease.
~bnoclonal Antibodies to Non-Small Cell Lung Car- cinomas. Namikawa, S., Rao, U., Chen, S., Pollard, C., Takita, H., Bankert, R.B. Roswell Park Memorial Institute, Buffalo, New York.
Three different monoclonal antibodies, 5C7, 5E8, and IF10 generated against primary adenocarcinoma, squamous cell carcinoma and large cell carcinoma of lung, respectively were assayed on fresh frozen tissue obtained from 36 lung cancers and 40 con- trol specimens employing double antibody immuno- peroxidase technique. Intensity of positive reac- tion and its pattern of distribution was roughly quantitated and also simultaneously compared to the pattern of distribution of keratins AEland AE 3 (Hybritech) and antikeratin and CEA (D/IKO) and preliminary findings are reported. Cross sections occurred but antibodies did not react with sarco- mas, melanoma and lymphomas. Antibody 5C7 reacted strongly with well differentiated adenocarcinoma and large cell carcinoma and with less intensity with squamous cell carcinoma. Intensity of stain- ing appeared to be proportional to the differen- tiation of the neoplasm. 5E8 also reacted with all cell types of lung cancer, but higher scores were obtained with squamous cell carcinoma. On the con- trary, about 60% of well differentiated adenocar- cinoma were negative, iF10 reactions were stron- gest with the poorly differentiated adenocarci- noma/large cell group. No significant differences in staining reactions of primary or metastatic lung carcinoma was found. Interesting findings were focal areas of positivity with Caltitonin (Histotech) in four cases of squamous cell carci- noma of lung and ~HCG in a single case of large cell carcinoma. Correlation of above findings with clinical behavior of the tumors will be presented.
A Canine Lung Cancer ~bdel. Benfield, J., Harmnond, W., DeCaro, L., Paladugu, R.
Pak, H., Teplitz, R.. City of Hope National Medical
45
Center, Duarte, California 91010, U.S.A. Progress against lung cancer requires
clinical/basic-science focus upon pre- neoplasia and early cancers, impossible to achieve with studies limited to humans. Therefore, a canine squamous cell lung cancer model has been developed. We have studied 104 dogs exposed by 9 regimens to the focal endobronchial chemical car- cinogens benzopyrene (BP), nitrosome- thylurea (NMU), methylcholanthrene (MCA), and dimethylbenzanthracene. The first cancer was induced by BP and NMU in 1/7 (14%) dogs after 5-~ years, but the most recent regimen (30mg MCA q 2-3 wks) produced 8/10 (80%) cancers within 2 years of first exposure; 2 recent can- cers are being serially passaged in athy- mic nude mice, now at the fourth trans- plant generation, and the model has been successfully used in 15 dogs in pre- clinical trials to show the safety and efficacy of a new high pressure bronchial washing system for sampling the bronchi- al epithelium. The predictable, repro- ducible, eventually metastasizing neo- plastic continuum begins with columnar and basal hyperplasia and squamous meta- plasia; it evolves into squamous meta- plasia with atypia in 6-18 weeks. The interval (about 20 months) until invasive cancer develops provides unique opportu- nity to sample repetitively from the preneoplastic bronchial mucosa. Serial cytologic specimens studied by image ana- lysis have revealed progressive increase in mean DNA content from normal (diploid) to atypical squamous metaplasia to cancer (>tetraploid) with significant (p<0.01) differences between diagnostic catego- ries.
We now have a large animal model of squamous cell carcinoma amenable to sur- gical methods; the reproducible preneo- plastic events occur in a time span short enough to be fiscally defensible, and long enough to permit biologic dissection during the development of bronchogenic cancers at predictable, preselected sites.
Growth In Nude Mice and Resistance Pre- dictive Tests of Non Small Cell hmg Carcinoma (NSCLC) Related to Prognosis. Drings, P., Mattern, J., Sonka, J., Vogt- Moykopf, I., Wayss, K., Volm, M. Chest Hospital Rohrbach, German Cancer Research Center, Heidelberg, FRG.
The purpose of the study was to assess the clinical prognostic significance of growth of NSCLC into nude mice as well as of a short term predicting resistance.
One hundred seventy one primary untreat- ed NSCLC were heterotransplanted into nude mice with an overall success rate of 46%.
Fifty cases (=29%) could be maintained
by serial transplantation. Lung tumors were divided into two groups depending on whether they have shown growth or not and correlated with the survi- val time of the corresponding patients. A relation- ship does not exist between growth of the tumors in nude mice or establishment of cell lines and prognosis of patients.
Furthermore, a total of 178 lung carcinomas we- re investigated by means of a short term test for predicting resistance. The basic feature of this short term test for predicting resistance is mea- surement of changes in incorporation of radioac- tive nucleic acid precursors after addition of cy- tostatic agents by scintillation counting. Patients with in vitro resistant tumors died earlier than those with sensitive tumors.
In conclusion, short term test for predicting resistance represent a useful tool in addition to current tumor parameters of estimating prognosis of patients with NSCLC whereas growth of SCLC into nude mice has not prognostic significance.
Biological Characterization of Transformed Rat Tracheal Epithelial (RTE) Cell Colonies in Cultu- re. Fitzgeral, D.J., Kitamura, H., Barrett, J.C., Nettesheim, P. Natl. Inst. Env. Hlth. Sci., Res. Triangle Pk., NC 27709, U.S.A.
In an accompanying abstract (Kitamura et al.,) the morphologic features of nontransformed (Types I-II) and transformed (types III-IV) RTE cell co- lonies which emerge 3-5 wks after MNNG treatment of primary RTE cell cultures, are described. In this study, we examined some biological characte- ristics of these different types of RTE cell colo- nies.
Five weeks after exposure of RTE cell cultures to MNNG, colonies were identified under phase mi- croscopy. Some colonies were incubated for 24 hrs with H-thymidine and were processed for autoradio- graphy to determine labelling indices, which were as follows (% labeled cells); type I 7 ~ 6, type II 21 + 13, type IIl 28 + 8, type IV 27 ~ 9. To determi--ne the fate of th~ different types of colo- nies, colonies were classified at 5 wks and main- tained for an additional 4 wks. Of the type I colonies, 20/27 senesced, 6/27 failed to grow, and 1/27 progressed to type III. Of the type II colo- nies, 3/22 regressed, 7/22 failed to grow, while 12/22 progressed to become types III-IV. Cells from different colony types were replated to assess the proportions of colony fo~nning units (CFU) and transformed CFU (i.e., CFU able to form trans- formed colonies). The data indicate that such pro- portions are similar for type II-III colonies but are considerably larger in type IV colonies.
These results support the notion based on mor- phologic studies that type I colonies are relative- ly inactive. Type II colonies, however, which so far have also been judged to be nontransformed, require reappraisal since they have labelling in- dex and CFU fraction similar to type III colonies; furthermore, in 50% of the cases, they progress to type III-IV colonies.
