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Biomedical subjects

K R McIntire

Publications and source records attributed to K R McIntire.

At least 19 recordsLinked to original sources
PubMed1988

Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer.

Sera from 71 patients with localized lung cancer, from 70 normal controls, and from 73 patients with benign lung diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen (CEA). Individual markers were studied, and optimal combinations of markers were sought for discriminating patients with localized lung cancer from normal controls and from patients with benign lung disease. Both logistic regression and recursive partitioning methods for discrimination were tried. The best rules involved only CEA and ferritin for discriminating patients with lung cancer from normal controls, and CEA and age for discriminating patients with lung cancer from those with benign lung diseases. The performance of these rules was validated on an independent serum panel containing sera from 56 patients with localized lung cancer, 75 normal controls, and 75 patients with benign lung diseases. Three rules designed to achieve 95% specificity against normal controls attained 14%-36% sensitivity for localized lung cancer in the validation panels, whereas three rules designed to achieve 95% specificity against benign lung diseases attained 30%-39% sensitivity. Some aspects of potential clinical applications are discussed.

Age Factors↗
PubMed1986

Trophoblastic proteins as tumor markers in nonseminomatous germ cell tumors.

In order to examine the relative usefulness of measurements of oncoplacental proteins as tumor markers in patients with nonseminomatous germ cell tumors, the authors measured alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), pregnancy-specific beta 1-glycoprotein (SP1), human placental lactogen (hPL), and placental cystine aminopeptidase (oxytocinase, CAP) in serial blood samples obtained from 26 men with these neoplasms. HCG and AFP were each elevated in 62% of the patients and both were elevated in 38%. SP1 and hPL were increased in 31% and 12%, respectively. None of the patients had elevated CAP activity. Serum hCG and SP1 concentrations were strongly correlated (r = 0.78, P less than 0.001). No patient had an elevated SP1 without a concomitant elevation in serum hCG. Serial measurements of hCG and SP1 indicated that they were concordant in five of the eight patients in whom both were elevated, and AFP and hCG were concordant in only one half of the ten patients in whom both markers were elevated. The number of patients with hPL elevations were too few for meaningful comparison of this marker with the others. These results indicate that measurements of SP1, hPL, and CAP do not provide additional useful information over that obtained from measurements of hCG and AFP in patients with nonseminomatous germ cell tumors.

Chorionic Gonadotropin↗
PubMed1986

Multiple markers for lung cancer diagnosis: validation of models for advanced lung cancer.

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.

Aged↗
PubMed1985

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival.

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with improved survival included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoprotein levels. Patients living longer than 12 months fell into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five "long-term" survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alpha-fetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum bilirubin determination can identify those with some prospect of prolonged survival.

Adolescent↗
PubMed1983

Collaborative study for the evaluation of multiple simultaneous markers in lung cancer.

The search for tumor markers suitable for use in diagnosis and management of patients with lung cancer has met with limited success because each available marker lacks sufficient sensitivity and specificity. We have begun a collaborative study to evaluate multiple simultaneous serum markers to determine whether there is a combination that will increase both sensitivity and specificity to the degree that noninvasive serologic tests might provide a means for managing patients with lung cancer. The National Cancer Institute, Bethesda, Maryland, has established a Serum Bank which can supply identical aliquots of the same serum sample to several different laboratories to perform quantitative assays for a number of markers. The results of these assays will serve as a data base to be analyzed for selection of the optimal grouping of markers for the different types of lung cancer and for evaluation of different biostatistical techniques to maximize the benefit derived by multiple marker determination. The evaluation of multiple markers will be carried out in several separate steps: (a) determination of a combination of markers that discriminate advanced lung cancer from benign lung disease; (b) demonstration of the ability of that combination to define early or localized lung cancer; (c) selection of a combination that best separates lung cancer from cancer of other sites; (d) testing of combined markers for the ability to predict response to therapy, including detection of early recurrence before clinical signs appear; and (e) evaluation of the combination(s) for effectiveness in detecting lung cancer in asymptomatic individuals. The experimental design and selection of markers will be presented and discussed.

Adenocarcinoma↗
PubMed1982

Identification and purification of a human lung tumor-associated antigen from a primary lung tumor.

A human lung tumor-associated protein has been purified from an extract of a human small cell carcinoma of the lung and shown by Ouchterlony double diffusion analysis to be antigenically identical to a component which was previously demonstrated in 84 of 98 lung tumor extracts of all histological types but absent from extracts of normal adult and fetal lung, other normal tissues, and tumors of other organs. These studies utilized xenoantisera raised against a pool of lung tumor extracts which were exhaustively adsorbed with normal serum and tissue extracts. A radial immunodiffusion assay developed for the antigen permitted its quantitation throughout the course of isolation. Purification was accomplished by ion-exchange chromatography, gel filtration, and affinity immunoadsorption. By ion-exchange chromatography, the proteins appeared to be quite heterogeneous, with immunological reactivity detected in three different peaks. However, all the active components were immunologically identical. Gel filtration of the major antigenic component from diethylaminoethyl cellulose similarly demonstrated a further fractionation into several active, immunologically identical forms. These results suggest a charge-size isomeric relationship among the various forms, all of which possess a common and identical antigenic site. The major component was isolated throughout the purification scheme. The final product represented 9% of the input activity, produced a single, although broad, protein-staining region on 7% polyacrylamide gels which was coincident with antigenic activity, and exhibited immunological identity with the antigen in the crude extract as well as with that in an extract from another lung tumor.

Antigens, Neoplasm↗
PubMed1982

Characterization of a human lung tumor-associated antigen and development of a radioimmunoassay.

A human lung tumor-associated antigen (LTA), previously isolated from a small cell carcinoma, was further studied after labeling with N-succinimidyl-3-(4-hydroxy-5-[125I]iodophenyl)propionate. Two immunoreactive forms of the labeled antigen were observed and isolated after electrophoresis in 7% polyacrylamide gels. These components, referred to as LTA-I and LTA-II in order of mobility, were judged homogeneous by gel electrophoresis, G-200 gel filtration, size exclusion high-performance liquid chromatography, and sedimentation velocity analysis. The latter three techniques produced identical profiles for both forms of the LTA. Sephadex chromatography and high-performance liquid chromatography analyses indicated the mass of the antigens to be approximately 140,000 to 150,000 daltons with a D20,w of 4.2 to 4.3 x 10(-7) sq cm/sec. The S20,w values for both were 4.5 to 4.6S. Sodium dodecyl sulfate gel electrophoresis of LTA-II gave a single component with a molecular weight of 81,700, while LTA-I had a major component identical in size to LTA-II and two minor components with molecular weights of 50,000 and 27,700, respectively. The isoelectric point of LTA-II (peaks at pH 2.6 and 3.2) generally was more acidic than LTA-I (major component centered at pH 4.7, minor component centered at pH 3.1). A radioimmunoassay, with a useful detection range of from 1 to 100 ng/ml, was developed with LTA-I. This assay was used to determine the concentration of LTA in the sera of normal and lung cancer patients. Fifteen normal sera had a mean of 17 +/- 22 (S.D.) ng/ml, with none greater than 83 ng/ml (+3 S.D.). Thirteen lung cancer patients with Stage I (i.e., localized disease) had a mean of 187 +/- 219 ng/ml, with the means for 7 of 13 patients being greater than 83 ng/ml; 15 lung cancer patients with Stage III, more extensive disease, had a mean of 277 +/- 252 ng/ml, with the means for 12 of 15 patients being greater than 83 ng/ml. This antigen may be useful for the early detection or monitoring of lung cancer.

Antigens, Neoplasm↗
PubMed1982

Studies on a purified human lung tumor-associated antigen.

A human lung tumor-associated antigen has been identified by Ouchterlony analysis in 86% of lung tumor extracts of all histologic types. It was not detected by this method in extracts of normal adult or fetal lung, 12/13 other tumors, normal tissues or in normal serum. The antigen was purified from the extract of an undifferentiated small cell lung carcinoma by DEAE-cellulose. Sephadex G-200, and antibody affinity chromatography. The purified antigen exhibited size and charge heterogeneity, yet all isolated forms produced precipitin lines of identity with each other, as well as with an extract of an unrelated squamous cell carcinoma of the lung. The major form had a Mr of 150 000 by gel filtration and 81 700 by detergent gel electrophoresis. By radioimmunoassay, elevated levels of antigen were detected in 0/15 normal sera, 7/13 stage I and 12/15 stage III lung cancer sera. The urine of a different patient with a small cell lung carcinoma contained a related antigenic activity, but the major component was 30 000-50 000 daltons. The antigen has also been detected in extracts of a continuous cell line from a large cell carcinoma of the lung (ChaGo). The antigen is being evaluated for its usefulness as a lung tumor marker.

Animals↗
PubMed1981

Elaboration of human chorionic gonadotropin by lung tumors: an immunocytochemical study.

The highly sensitive peroxidase-antiperoxidase immunocytochemical method was used to demonstrate the presence of the beta-subunit of human chorionic gonadotropin (HCG) within paraffin sections of human lung tumors of diverse histologic patterns. Of the 61 tumors studied, 51 (84%) displayed HCG-like immunoreactivity. This is a much higher incidence than was expected considering studies by other investigators in which serum samples from patients with lung cancer were assayed for HCG. Our results are, however, consistent with data from studies by other investigators in which tumor extracts were assayed for HCG. In addition, it was found that HCG production was often linked with glycogen storage within tumor cells. This may explain the association of HCG production with large-cell carcinomas of the lung, because these tumors often contain copious quantities of glycogen.

Carcinoma, Bronchogenic↗
PubMed1980

Protein-A antibody-binding TPAAB) technique for detection of tumor-associated membrane antigen (TAMA) of Lewis lung carcinoma.

Xenoantisera were prepared in rabbits against intact paraformaldehyde-fixed Lewis lung carcinoma (LLCa) cells and membrane solubilized proteins extracted with Triton X-100 and 3M KCI. The antisera were analyzed for antibodies to tumor-associated membrane antigens (TAMA) by means of a solid-phase radioimmunoassay (RIA). THe immunoassay employed 125-labelled Staphylococcus aureus protein A (SPA) to detect specific antibody binding to glutaraldehyde-fixed Lewis lung tumor target cells. The protein-A antibody-binding (PAAB) method is rapid, sensitive and reproducible. The PAAB revealed a possible LLCa-TAMA as evidenced by the reactivity of xenoantisera raised to LL paraformaldehyde tumor cell vaccine (TCV) and LL tumor Triton X-100 (TTri) and 3M KCI (TKCI) extracts of membrane preparations. The reactivity of our antisera followed linear dose-response kinetics but the degree of reactivity decreased from anti-TCV to anti-TTri to anti-TKCI respectively. The LL-TAMA demonstrated specificity since our antisera did not significantly cross-react with normal C56BL/6 cellular antigens or other known murine tumor-associated surface antigens of virally and chemically-induced tumor systems.

Animals↗
PubMed1980

Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates.

The carcinogenic potential of cycasin and methylazoxymethanol (MAM) acetate was investigated in nonhuman primates. Old-world monkeys (rhesus, cynomolgus, and African green monkeys) received cycasin and/or MAM acetate by oral or ip routes up to 11 years. Eighteen monkeys survived longer than 2 months after initiation of treatment with cycasin (50-75 mg/kg) or MAM acetate (1.5-3.0 mg/kg) given orally 5 days/week; 9 of the animals were necropsied. Histopathologic examination of a liver tumor from 1 of these monkeys revealed well-differentiated hepatocellular carcinoma. A second monkey had multiple tumors, including hepatocellular carcinoma, intrahepatic bile duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous polyps of the colon. Although liver tumors were not observed in the other monkeys, all but 1 monkey had hepatic lesions such as toxic hepatitis and cirrhosis. These monkeys had received cycasin and/or MAM acetate for an average of 57 months (range, 2-133 mo). A group of 10 monkeys received MAM acetate by weekly ip injections (3-10 mg/kg). Six of these animals developed tumors after receiving an average of 6.14 g (range, 3.58-9.66 g) of MAM acetate for an average of 75 months (range, 50-89 mo). Four of the monkeys developed hepatocellular carcinomas, and 2 had multiple primary tumors including hepatocellular carcinomas, renal carcinomas, squamous cell carcinomas of the esophagus, and adenocarcinomas of the small intestine. Our results showed that long-term administration of cycasin and/or MAM acetate by oral and ip routes was hepatotoxic and carcinogenic in old-world monkeys.

Animals↗
PubMed1980

Theoretical limitations in the immunodiagnostic imaging of cancer with computed tomography and nuclear scanning.

In order to help assess the feasibility of using immunologically tagged agents to render tumors detectable with current computed tomographic and nuclear scanners, mathematical formulations were developed to determine the theoretical limits of tumor detection relative to size and depth of the lesions. The results of our analysis suggest that visualization with computed tomography of a tiny tumor (1 sq mm, cross-sectional area) would require binding in the order of 2 x 10(5) iodine atoms/antigenic site, while imaging of a very large (900-sq mm) tumor would require approximately 10(4) atoms/site. Very low energy scanners might reduce these discouraging estimates by an order of 10(2). The immunological imaging of tumors with nuclear scanning appears quite feasible from our formulations, as has been demonstrated by others clinically. Small (1-sq cm) and deep (greater than or equal to 5-cm) tumors appear detectable with uptake ratios of the order of 5 or higher, which seem to be attainable currently. Smaller and deeper tumors require much higher uptake ratios to be detected.

Antibodies, Neoplasm↗
PubMed1980

Tumor markers for radiommunodetection of cancer.

One of the potential uses of tumor-associated antigens or tumor markers, the localization of metastatic tumors using radioactive antibodies, has now been demonstrated and confirmed in clinical situations. The next stage of development in radioimmunodetection will be the improvement of techniques and methodologies. The selection of the optimal marker or markers to be used for localization is one area where improvement will be forthcoming. Guidelines for the choice of potential markers and methods for evaluation of potential markers before being clinically tested are presented in this article.

Antibodies, Neoplasm↗
PubMed1979

Immunochemical characterization of tumor-associated surface antigens on a Moloney leukemia virus-lymphoma, MBL-2.

Tumor-associated surface antigens (TASA) on a Moloney leukemia virus (M-MuLV)-induced lymphoma, MBL-2, in C57BL/6 mice (B6) were characterized. The surface proteins of MBL-2 cells were selectively radioiodinated and then extracted by Nonidet P40. The solubilized materials were then reacted with a variety of antisera: monospecific antisera to murine leukemia viral proteins (anti-gp69/71, anti-p30, anti-p15, anti-p12 and anti-p10), sera from B6 which regressed murine sarcoma tumors induced by murine sarcoma virus (anti-MSV) and a rabbit anti-MBL-2 antiserum. The resulting radioimmune precipitates were analyzed and compared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The following results were obtained. (1) Among all anti-viral protein antisera tested only anti-gp69/71 was active and detected a protein doublet of gp69/71 and its degradation fragments of 42,000 and 35,000 daltons. (2) Radioimmune precipitates prepared with anti-MSV showed a SDS-PAGE pattern similar to that seen with anti-gp69/71. This result indicated that the surface antigen detected by the anti-MSV serum on MBL-2 tumor cell was probably a viral envelope antigen. (3) The rabbit anti-MBL-2 serum detected on the cell membrane an antigen of approximately 95,000 daltons which was tumor-associated and did not appear to be related to virion components. The anti-MBL-2-serum still reacted with the 95,000 dalton antigen after absorption with disrupted M-MuLV virus and with gp69/71 and p30 purified from the virus.

Animals↗