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Biomedical subjects

F Searle

Publications and source records attributed to F Searle.

51 records · Page 3Linked to original sources

Radioimmunolocalization of tumours by external scintigraphy after administration of 131I antibody to human chorionic gonadotrophin: preliminary communication.

(131)Iodine ((131)I) labelled antibody directed against human chorionic gonadatrophin (hCG) was given on 21 occasions to 18 patients with hCG-producing neoplasms. Tumours were localized by external scintigraphy in 13 of 21 investigations. Positive results were obtained reliably when serum hCG exceeded 500 miu/ml and in some cases sensitivity was comparable to that of computerized tomography. A positive result probably implies viability in the tumour and this was of practical value in discriminating between necrotic deposits and living tumour before surgery.

Antibodies↗

Preliminary therapeutic and localization studies with human chorionic gonadotrophin.

Studies in both patients and mice have been carried out using heterologous antibody directed at secreted products of tumors. In preliminary therapeutic studies in patients with drug-resistant choriocarcinoma and malignant teratoma, heterologous anti-human chorionic gonadotrophin (HCG) and anti-alpha-fetoprotein have been combined with continued cytotoxic chemotherapy. The results to date, although interesting, are inconclusive. In nude mice, anti-HCG administration at the time of inoculation with choriocarcinoma cells failed to inhibit tumor growth. 131I-Labeled anti-HCG and anti-carcinoembryonic antigen have been used in localization studies. Specific:nonspecific ratios of up to 2:1 were obtained in human and murine studies with HCG- and carcinoembryonic antigen-producing tumors.

Animals↗

Serum-SP1-pregnancy-specific-beta-glycoprotein in choriocarcinoma and other neoplastic disease.

A radioimmunoassay for a plancental glycoprotein, beta1SP1, capable of detecting 2 microgram/l of the glycoprotein in serum was used to measure concentrations of beta1,SP1 in patients with choriocarcinoma, teratoma, colonic cancer, breast cancer, and ovarian cancer. 12 out of 94 (13%) healthy men and health non-pregnant women had detectable serum-beta1SP1 concentrations. Concentrations up to 50 000 microgram/l were found in the sera of patients with hydatidiform mole, invasive mole, choriocarcinoma, and malignant teratoma. beta1-glycoprotein concentrations were generally much lower than corresponding concentrations of chorionic gonadotrophin which is the most reliable marker for trophoblastic tumours. In a few cases, however, beta1-glycoprotein measurements may be useful in the detection of minimal residual tumour. The slightly raised values found in some patients with carcinoma of the colon, breast, or ovary seem unlikely to be useful for diagnostic purposes of for monitoring the course of these cancers.

Beta-Globulins↗

Beta-human chorionic gonadotrophin and carcino-embryonic antigen in the management of ovarian carcinoma.

Measurements of HCG and carcino-embryonic antigen (CEA) were made in 26 patients with ovarian cancer to evaluate these substances as tumour markers; 13-4 per cent of 194 CEA estimations and 14-6 per cent of 144 HCG estimations were abnormal. CEA values were abnormal in 9 out of 26 patients and HCG values in 13 out of 26 patients. The implications of these findings particularly the presence of HCG are discussed.

Adenocarcinoma↗

Carcinoembryonic antigen: isolation of a sub-fraction with high specific activity.

Four sub-fractions of carcinoembryonic antigen have been obtained by chromatography of conventional CEA on Con A-Sepharose and their immunoreactive contents have been determined. Comparative studies have shown that a fraction eluted with 2% methyl glucoside (CEA 2B) had the highest activity, with a potency (60 u/mug) twice that of unfractionated CEA although appreciable activity was also found in the other fractions. The amino acid composition of CEA 2B is similar to that reported for conventional CEA but there is a lower content of neutral hexoses and a comparatively high content of N-acetylglucosamine. Experiments with a pool of sera from 11 patients with colonic cancer, which had been fractionated on Con A-Sepharose, have shown that nearly all the CEA activity was contained in a fraction eluted with 2% methyl glucoside. A convenient method of isolating CEA with high specific activity directly from perchloric acid extracts of tumour tissue is also described.

Acetylglucosamine↗

N-(2-hydroxypropyl)methacrylamide copolymer-6-(3-aminopropyl)-ellipticine conjugates. Synthesis, in vitro, and preliminary in vivo evaluation.

Ellipticine derivatives have potential as anticancer drugs. Their clinical use has been limited, however, by poor solubility and host toxicity. As N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-anticancer conjugates are showing promise in early clinical trials, a series of novel HPMA copolymer conjugates have been prepared containing the 6-(3-aminopropyl)-ellipticine derivative (APE, NSC176328). Drug was linked to the polymer via GFLG or GG peptide side chains. To optimize biological behavior, HPMA copolymer-GFLG-APE conjugates with different drug loading (total APE: 2.3-7% w/w; free APE: <0.1% w/w) were synthesized. Conjugation of APE to HPMA copolymers considerably increased its aqueous solubility (>10-fold). HPMA copolymer-GG-APE did not liberate drug in the presence of isolated lysosomal enzymes (tritosomes), but HPMA copolymer-GFLG-APE released APE to a maximum of 60% after 5 h. The rate of drug release was influenced by drug loading; lower loading led to greater release. Whereas free APE (35 microg/mL) caused significant hemolysis (50% after 1 h), HPMA copolymer-APE conjugates were not hemolytic up to 300 microg/mL (APE-equiv). As would be expected from its cellular pharmacokinetics, HPMA copolymer-GFLG-APE was >75 times less cytotoxic than free drug (IC(50) approximately 0.4 microg/mL) against B16F10 melanoma in vitro. However, in vivo when tested in mice bearing s.c. B16F10 melanoma, HPMA copolymer-GFLG-APE (1-10 mg/kg single dose, APE-equiv) given i.p. was somewhat more active (highest T/C value of 143%) than free APE (1 mg/kg) (T/C =127%). HPMA copolymer-APE conjugates warrant further evaluation as potential anticancer agents.

Acrylamides↗