Detection of lung cancer in clinical specimens using a human monoclonal antibody HB4C5-clone 3

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133 Human alveolar macrophages of anergic patients with lung cancer lack the responsiveness to recombinant interferon gamma Kawatsu H, Hasegawa Y, Takagi E, Shimokata K. 1st Deparrment of Internal Medicine, Nagoya Universify School of Medicine, Showa-ku, Nagoya 466. Chest 199l;lC0:1277-80. We studied the effect of recombinant interferon gamma (rIFN- gamma) on the phagocytic and bactericidal actions in human alveolar macrophages (AM) of patients with pulmonary tuberculosis and lung cancer. Treatment with 106 or I .ooOU/ml of rIFN-gamma for 24 hours resulted in an increased percentage of AM ingesting bacillus Calmette- Guerin (BCG) and an increased number of ingested BCG in individual AM in tuberculin-positive patients with lung cancer and pulmonary tuberculosis. The dFN-gamma treatment also showed increased killing activity of AM in tttbercttlin-positive patients. However, rIFN-gamma treatment of AM in tuberculin-negative anergic patients with lung cancer did not induce the increase of phagccytic and killing activities against BCG. These results suggest that responsiveness and activation of AM to rIFN-gamma are inhibited in the anergic environment. Tumor-associated trypsin inhibitor (TATI) in the diagnosisof lung cancer Pecchio F, Rapellino M, Baldi S, Casali V, Libertucci D, Coni F. CiinicalChemist~,Moline~teNospiral,C.Llramante84.10126Torino. Stand J Clin Lab Invest Suppl 1991;51:63-4. To evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) as a marker for the diagnosis of lung cancer we determined serum levels of this peptide in 225 patients with lung cancer and in 74 patients with chronic obstructive lung disease. A reference population consisting of 15I healthy volunteers was also studied. TAT1concentra- tions were measured by radioimmunoassay. As a cut-off point we used the 99th percentile of the TAT1 concentrations in a reference popula- tion, which was 32 pg/I. TAT1 does not appear to be a good tumor marker in lung cancer. Its sensitivity is poor in comparison with CEA and TPA. The correlation between TATI levels and stage of the disease and histological type was weak. Synchronous lung cancers defined by deoxyribonucleic acid flow cytometry Ichinose Y, Hara N, Ohta M. Deparfmenr of Chest Surgery, National Kyushu Cancer Cenrer. l-1, 3-Chome, Norame. Minami-ku, Fakuoka 815. J Thor= Cardiovasc Surg 1991:102:418-24. When two pulmonary tumors are seen simultaneously in patients with lung cancer, it always raises a question as to whether the lesions are synchronous lung cancers or lung cancer with intrapulmonary metasta- sis. To settle this issue, we used deoxyribonucleic acid flow cytometry. Deoxyribonucleic acid ploidy patterns of tumors were able to be analyzed in I4 patients with two simultaneous pulmonary tumors resected by operation. These two tumors, with completely different patterns of deoxyribonucleic acid ploidy, were defined as synchronous lung cancers. Tumors were defined as lung cancer with intrapulmonary metastasis when both tumors showed diploidy or when at least one deoxyribonucleic acid index ofabnormal clones between twoaneuploid tumors was the same or almost identical. Tumors of the five patients with stage I disease were classified as synchronous lung cancers according to the criteria involving deoxyribonucleic acid flow cytome- try. Both tumors were adenocarcinomas in four patients and large-cell and squamous cell carcinomas in one. Both tumors in four patients were located in the same lobe but different segments. All but one patient with different histologic types are alive without recurrence from 24 to 100 months after operation. Tumors of the nine patients with stage III disease m whom intrapulmonary metastasis was clinically suspected were classified as lung cancer with intrapulmonary metastasts accord- ing to the criteria. These data suggest that deoxyribonucleic acid flow cytometry of tumors may have diagnostic value in determining syn- chronous lung cancers, Detection of lung cancer in clinical specimens using a human monoclonal antibody HBQCS-clone 3 Hirose H, Sato S, Tai H, Okano H, Yasumoto K, Murakami H et al. Uorinaga Insdfue ofBiological Science, Shinwsueyoshi. 2-l-l. Tswumi- ku, Yokohama 230. Hum Antibodies Hybridomas 1991;2:200-3. Biopsies of I8 patients with lung cancer and cellular specimens of 2 1 lung cancer patients were analyzed with human monoclonal antibody HB4C5-clone 3 using avidin-biotin-peroxidasc techniques. Analyses with the biopstes showed that HB4C5-clone 3 reacted with 16 of I8 biopsy specimens at a high rate of about 90% and reacted with all specimens of five adenocarcinoma tissues, five of six squamous cell carcinomas, twoof three largecell carcinomas, both specimensof small cell carcinomas, and both of the other types of carcinomas. In all the reactive cases, the moncclonal antibody was reactive with greater than 50% of cancer cells. With cellular specimens of lung cancer patients, HB4C5-clone 3 reacted with 7 of 13 adenocarcinomaspecimens, two of six squamous cell carcinomas, and one of two small cell carcinomas. The immunoreaction with HB4C5-clone 3 was observed in sites of the cytoplasm of cancer cells. From these data, HB4C5-clone 3 is consid- ered tobeofpotential use indiagnosesoftissuesandcellularspccimens of lung cancer. Induced sputum and cytological diagnosis of lung cancer Khajotia RR, Mohn A, Pokieser L, Schalleschak I, Vetter N. 2nd Departmenr of Chest Medicine, Pulmologisches Zentram, Sanaforium- sInwe 2. A-1145 Vienna. Lance1 1991;338:976-7. Diagnosis of lung cancer by examination of induced sputum speci- mens for maIiguattt cells may be a valuable alternative to diagnosis by bronchoscopy. Patients suspected of having lung cancer were recruited and randomly distributed into two groups, one groups (n = 34) having sputum induced by use of an ultrasonic nebuliser before bronchoscopy, and the other (n = 33) undergoing ordinary expectoration before bronchoscopy. 25 patientsin the induced-sputum groupwerediagnosed as having primary lung cancer; induced sputum was positive for malignant cells in 21 of these patients (84%). whereas bmnchoscopy was positive in 23 (92%) (not significantly different). In comparison, ordinary sputum was positive in 15 of 29 patients (52%) diagnosed as having primary lung cancer, whereas bronchoscopy was positive in 28 (97%) (p < 0.001). Induction of sputum by an ultrasonic nebuliser was an effective procedure for diagnosis of primary lung cancer. Surgery Useof Medicareclaimsdata toevaluateoutcomes in elderly patients undergoing lung resection for lung cancer Whittle J, Steinberg EP. Anderson GF, Herbert R. 1830 Ea.rf Monumcnr Srreef, Baltimore, MD 21205. Chest 1991;100:729-34. Objective: To estimate, using Medicare claims data, the outcomes in elderly Americans undergoing lung resection for lung cancer. Design: We used discharge diagnosis and procedure codes in 1983 to 1985 Medicare hospital (pan A) claims records to identify patients who underwent lung resection for lung cancer; we assessed periop-erative, one-year, and two-year survival using Medicare enroIlment file data. Patients: From a nationally random sample of 1,138,COOMedicare beneficiaries over 65 years of age. we identified 1,290 individuals who fulfilledottrdefmition for lung resection for lung cancer. Measurements and Main Results: Overall @operative (30-day) mortality was 7.4 percent. Postoperative survival at one and two years was 69 percent and 54 percent, respectively. Male sex, older age, and pneumonectomy, as opposed to a lesser procedure, were associated with reduced periopem- tiveandone-yearandtwo-yearsurvival.Theadverseeffectofadvanced age on one-year and two-year survival following lung resection was not explained by tbe lower life expectancy of older individuals. Conclu- sions: Medicare claims data can be used to estimate likely outcomes for elderly patients undergoing surgery for lung cancer. Expected out- comes vary with the patient’s age, sex, and the type of surgical procedure performed.

Transcript of Detection of lung cancer in clinical specimens using a human monoclonal antibody HB4C5-clone 3

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Human alveolar macrophages of anergic patients with lung cancer lack the responsiveness to recombinant interferon gamma Kawatsu H, Hasegawa Y, Takagi E, Shimokata K. 1st Deparrment of Internal Medicine, Nagoya Universify School of Medicine, Showa-ku, Nagoya 466. Chest 199l;lC0:1277-80.

We studied the effect of recombinant interferon gamma (rIFN- gamma) on the phagocytic and bactericidal actions in human alveolar macrophages (AM) of patients with pulmonary tuberculosis and lung cancer. Treatment with 106 or I .ooO U/ml of rIFN-gamma for 24 hours resulted in an increased percentage of AM ingesting bacillus Calmette- Guerin (BCG) and an increased number of ingested BCG in individual AM in tuberculin-positive patients with lung cancer and pulmonary tuberculosis. The dFN-gamma treatment also showed increased killing activity of AM in tttbercttlin-positive patients. However, rIFN-gamma treatment of AM in tuberculin-negative anergic patients with lung cancer did not induce the increase of phagccytic and killing activities against BCG. These results suggest that responsiveness and activation of AM to rIFN-gamma are inhibited in the anergic environment.

Tumor-associated trypsin inhibitor (TATI) in the diagnosis of lung cancer Pecchio F, Rapellino M, Baldi S, Casali V, Libertucci D, Coni F. CiinicalChemist~,Moline~teNospiral,C.Llramante84.10126Torino. Stand J Clin Lab Invest Suppl 1991;51:63-4.

To evaluate the usefulness of tumor-associated trypsin inhibitor (TATI) as a marker for the diagnosis of lung cancer we determined serum levels of this peptide in 225 patients with lung cancer and in 74 patients with chronic obstructive lung disease. A reference population consisting of 15 I healthy volunteers was also studied. TAT1 concentra- tions were measured by radioimmunoassay. As a cut-off point we used the 99th percentile of the TAT1 concentrations in a reference popula- tion, which was 32 pg/I. TAT1 does not appear to be a good tumor marker in lung cancer. Its sensitivity is poor in comparison with CEA and TPA. The correlation between TATI levels and stage of the disease and histological type was weak.

Synchronous lung cancers defined by deoxyribonucleic acid flow cytometry Ichinose Y, Hara N, Ohta M. Deparfmenr of Chest Surgery, National Kyushu Cancer Cenrer. l-1, 3-Chome, Norame. Minami-ku, Fakuoka 815. J Thor= Cardiovasc Surg 1991:102:418-24.

When two pulmonary tumors are seen simultaneously in patients with lung cancer, it always raises a question as to whether the lesions are synchronous lung cancers or lung cancer with intrapulmonary metasta- sis. To settle this issue, we used deoxyribonucleic acid flow cytometry. Deoxyribonucleic acid ploidy patterns of tumors were able to be analyzed in I4 patients with two simultaneous pulmonary tumors resected by operation. These two tumors, with completely different patterns of deoxyribonucleic acid ploidy, were defined as synchronous lung cancers. Tumors were defined as lung cancer with intrapulmonary metastasis when both tumors showed diploidy or when at least one deoxyribonucleic acid index ofabnormal clones between twoaneuploid tumors was the same or almost identical. Tumors of the five patients with stage I disease were classified as synchronous lung cancers according to the criteria involving deoxyribonucleic acid flow cytome- try. Both tumors were adenocarcinomas in four patients and large-cell and squamous cell carcinomas in one. Both tumors in four patients were located in the same lobe but different segments. All but one patient with different histologic types are alive without recurrence from 24 to 100 months after operation. Tumors of the nine patients with stage III disease m whom intrapulmonary metastasis was clinically suspected were classified as lung cancer with intrapulmonary metastasts accord- ing to the criteria. These data suggest that deoxyribonucleic acid flow cytometry of tumors may have diagnostic value in determining syn- chronous lung cancers,

Detection of lung cancer in clinical specimens using a human monoclonal antibody HBQCS-clone 3 Hirose H, Sato S, Tai H, Okano H, Yasumoto K, Murakami H et al. Uorinaga Insdfue ofBiological Science, Shinwsueyoshi. 2-l-l. Tswumi- ku, Yokohama 230. Hum Antibodies Hybridomas 1991;2:200-3.

Biopsies of I8 patients with lung cancer and cellular specimens of 2 1 lung cancer patients were analyzed with human monoclonal antibody HB4C5-clone 3 using avidin-biotin-peroxidasc techniques. Analyses with the biopstes showed that HB4C5-clone 3 reacted with 16 of I8 biopsy specimens at a high rate of about 90% and reacted with all specimens of five adenocarcinoma tissues, five of six squamous cell carcinomas, twoof three largecell carcinomas, both specimensof small cell carcinomas, and both of the other types of carcinomas. In all the reactive cases, the moncclonal antibody was reactive with greater than 50% of cancer cells. With cellular specimens of lung cancer patients, HB4C5-clone 3 reacted with 7 of 13 adenocarcinomaspecimens, two of six squamous cell carcinomas, and one of two small cell carcinomas. The immunoreaction with HB4C5-clone 3 was observed in sites of the cytoplasm of cancer cells. From these data, HB4C5-clone 3 is consid- ered tobeofpotential use indiagnosesoftissuesandcellularspccimens of lung cancer.

Induced sputum and cytological diagnosis of lung cancer Khajotia RR, Mohn A, Pokieser L, Schalleschak I, Vetter N. 2nd Departmenr of Chest Medicine, Pulmologisches Zentram, Sanaforium- sInwe 2. A-1145 Vienna. Lance1 1991;338:976-7.

Diagnosis of lung cancer by examination of induced sputum speci- mens for maIiguattt cells may be a valuable alternative to diagnosis by bronchoscopy. Patients suspected of having lung cancer were recruited and randomly distributed into two groups, one groups (n = 34) having sputum induced by use of an ultrasonic nebuliser before bronchoscopy, and the other (n = 33) undergoing ordinary expectoration before bronchoscopy. 25 patientsin the induced-sputum groupwerediagnosed as having primary lung cancer; induced sputum was positive for malignant cells in 21 of these patients (84%). whereas bmnchoscopy was positive in 23 (92%) (not significantly different). In comparison, ordinary sputum was positive in 15 of 29 patients (52%) diagnosed as having primary lung cancer, whereas bronchoscopy was positive in 28 (97%) (p < 0.001). Induction of sputum by an ultrasonic nebuliser was an effective procedure for diagnosis of primary lung cancer.

Surgery

Useof Medicareclaimsdata toevaluateoutcomes in elderly patients undergoing lung resection for lung cancer Whittle J, Steinberg EP. Anderson GF, Herbert R. 1830 Ea.rf Monumcnr Srreef, Baltimore, MD 21205. Chest 1991;100:729-34.

Objective: To estimate, using Medicare claims data, the outcomes in elderly Americans undergoing lung resection for lung cancer. Design: We used discharge diagnosis and procedure codes in 1983 to 1985 Medicare hospital (pan A) claims records to identify patients who underwent lung resection for lung cancer; we assessed periop-erative, one-year, and two-year survival using Medicare enroIlment file data. Patients: From a nationally random sample of 1,138,COO Medicare beneficiaries over 65 years of age. we identified 1,290 individuals who fulfilledottrdefmition for lung resection for lung cancer. Measurements and Main Results: Overall @operative (30-day) mortality was 7.4 percent. Postoperative survival at one and two years was 69 percent and 54 percent, respectively. Male sex, older age, and pneumonectomy, as opposed to a lesser procedure, were associated with reduced periopem- tiveandone-yearandtwo-yearsurvival.Theadverseeffectofadvanced age on one-year and two-year survival following lung resection was not explained by tbe lower life expectancy of older individuals. Conclu- sions: Medicare claims data can be used to estimate likely outcomes for elderly patients undergoing surgery for lung cancer. Expected out- comes vary with the patient’s age, sex, and the type of surgical procedure performed.