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Biomedical subjects

T M Chu

Publications and source records attributed to T M Chu.

At least 91 records · Page 5Linked to original sources
PubMed1984

Simultaneous evaluation of a pancreas-specific antigen and a pancreatic cancer-associated antigen in pancreatic carcinoma.

A pancreas cancer-associated antigen (PCAA) and a pancreas-specific antigen (PaA) were simultaneously quantitated by enzyme-linked immunosorbent assays in serum specimens from 51 normal controls, 76 pancreatic cancers, 194 nonpancreatic cancers, and 22 benign pancreatic diseases. Primary immunological reagents used in the enzyme-linked immunosorbent assays were our polyclonal antibodies produced in rabbits against purified PCAA and PaA. Results revealed discordance of these two markers in pancreatic cancer, suggesting that the presence of these two biochemically and immunologically distinct pancreas proteins in patients' serum may reflect different biological aspects of cancer. The combination test resulted in a better sensitivity and specificity for pancreatic cancer, 90 and 85%, respectively, than either PCAA or PaA assay alone. This study demonstrated that the combination of serum PCAA and PaA tests yields an additive clinical value and may be a useful adjunctive aid for the immunodiagnosis of the pancreatic cancer.

Antigens, Neoplasm↗
PubMed1983

Purification and characterization of ribonucleases from human seminal plasma.

Four ribonucleases (RNAases I-IV) have been purified to homogeneity from human seminal plasma by precipitation with 40-75%-satd. (NH4)2SO4, followed by chromatographies on concanavalin A-Sepharose 4B, DEAE-cellulose phosphocellulose, agarose-5'-(4-aminophenylphospho)uridine 2'(3')-phosphate (RNAase affinity column) and Sephadex G-75 or G-100. The homogeneity of these RNAases was confirmed by polyacrylamide-gel electrophoresis. Mr values for these purified RNAases were 78 000, 16 000, 13 300 and 5000 as estimated by gel filtration. Enzyme activities of RNAases I, III and IV were inhibited by Mn2+, Zn2+ and Cu2+ and activated by Na+, K+, Ba2+, Mg2+, Fe2+ and EDTA, whereas that of RNAase II was inhibited by Ba2+, Mg2+, Fe2+, Mn2+, Zn2+ and Cu2+ and activated by Na+, K+ and EDTA. RNAases I, II and IV demonstrated a higher affinity for poly(C) and poly(U) or yeast RNA, whereas RNAase III preferentially hydrolysed poly(U) over poly(C) and yeast RNA. In the presence of 5 mM-spermine, RNAase I was dissociated to a low-Mr (5000) enzyme with an increase in total RNAase enzymic activity. Xenoantiserum to each RNAase was raised and evaluated by immunoprecipitation and immunohistochemical methods. Anti-(seminal RNAase III) antiserum showed no immunological cross-reaction with RNAases of other human origin, whereas anti-(seminal RNAase I), -(RNAase II) and -(RNAase IV) antisera exhibited indistinguishable immunological reactions with serum RNAase and other human RNAases, except that anti-(seminal RNAase I) and -(RNAase antisera IV) did not react with pancreatic RNAases. Seminal RNAases I and IV were identical immunologically as shown by anti-(RNAase I) and anti-(RNAase IV) in immunodiffusion. Immunohistochemical study revealed that, among human tissues examined, only prostate expressed seminal RNAase III. These results suggested that human seminal RNAase I may be an aggregated molecule of RNAase IV and that seminal RNAases II and IV are similar to serum RNAases, whereas seminal RNAase III is a prostate-specific enzyme.

Amino Acids↗
PubMed1983

The addition of chemotherapy to hormonal therapy for treatment of patients with metastatic carcinoma of the prostate.

Patients with advanced prostate carcinoma that had been stabilized by orchiectomy (ORCH) or hormone therapy for at least 3 months, were randomized to either diethylstilbestrol (DES) alone or DES plus Cytoxan or DES plus Emcyt. A total of 188 patients were randomized between July, 1976 and February, 1982 of which 161 were evaluable for objective response to treatment. Objective response rates, response duration, or survival experiences were not demonstrably different between treatment arms, either for all patients or within good or poor prognosis groups determined by initial pain or acid phosphatase level. Subjective improvements in performance status were small for each treatment. Pain relief was somewhat greater in the chemotherapy-hormone combinations than in the DES/ORCH, but the advantage was not statistically significant. Side effects were primarily nausea and vomiting and leukopenia, mostly in the DES + Cytoxan arm. The duration of stabilization prior to entry did not influence response overall, although there were opposing trends within each of the two chemotherapy arms. The premise for combining antitumor agents with hormones before hormone failure is still felt to be a more logical approach than waiting for the ultimate hormone failure, and a combination of hormones plus two antitumor agents is being evaluated in a subsequent ongoing trial where a more rigid design limits the duration of the preentry period of hormone stabilization.

Aged↗
PubMed1983

A comparison of estramustine phosphate versus cis-platinum alone versus estramustine phosphate plus cis-platinum in patients with advanced hormone refractory prostate cancer who had had extensive irradiation to the pelvis or lumbosacral area.

Single and combination chemotherapy was compared in a clinical trial for men with advanced, metastatic prostate cancer who had received prior pelvic irradiation and had had progression of disease despite hormonal therapy. The 149 patients were randomized to receive estramustine phosphate or cis-platinum alone or in combination. Of the 149 patients 25 (17 per cent) were excluded from the study but 124 were evaluated for response and survival. Entry variables were distributed similarly among patients in each treatment arm. There were no complete or partial responders but there were nearly twice as many patients whose disease was stabilized (33 per cent) on the combination regimen compared to estramustine phosphate (18 per cent) and about a third more than for cis-platinum (21 per cent). Analysis of survival revealed some advantage for patients on combination therapy. Major toxicities for all treatments were nausea and vomiting (62 to 88 per cent) and accompanying anorexia (72 to 95 per cent). Azotemia developed in 45 per cent of the patients receiving combination therapy. In addition an elevation in serum creatinine occurred in 22 per cent of the patients receiving combination therapy and in 17 per cent of those receiving cis-platinum alone. Myelosuppression occurred infrequently.

Aged↗
PubMed1983

Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer.

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.

Aged↗
PubMed1983

Experimental tumoricidal effects of monoclonal antibody against solid breast tumors.

Two distinct monoclonal antibodies (mAbs) were effective in the therapy of breast carcinomas of human origin established and growing in nude mice. Passive administration of either of the antibodies produced very rapid (less than 1 week) and significant reduction of in vivo tumor volume. Each of the mAbs showed in vivo targeting of the tumors. Histological analysis of mAb-treated tumors revealed extensive cellular necrosis. Each of the antibodies in vitro was effective in complement-mediated cytolysis at a concentration less than 1 ng/ml. The tumoricidal responses show that this is a useful model for passive human immunotherapy using mAbs.

Animals↗
PubMed1983

Monoclonal antibody (F5) to human prostate antigen.

Hybridoma culture F5 has been developed which secretes monoclonal antibody (McAb) directed to an epitope of a prostatic glycoprotein of Mr 34 kD (Prostate Antigen, PA). Tissue levels of PA have been evaluated using a competitive-binding enzyme-immunoassay based upon the inhibition of McAb binding activity to purified antigen. Results indicated the specific occurrence of high antigen concentrations in extracts prepared from prostatic tissues. The antigenicity of epitope F5 is resistant to tissue fixation and embedding protocols, and has been demonstrated upon immunoperoxidase staining procedures. Immunoperoxidase data strongly indicate that McAb F5 possesses a singular specificity towards prostatic epithelial cells. Other tissues, whether normal or cancerous, fail to express this determinant. Specimens examined included epithelial and nonepithelial tissues along with a panel of carcinomas and sarcomas. The antibody was able to detect tumor cells at extra-prostatic sites and represents a powerful probe for the detection and differential diagnosis of metastatic cancer of the prostate.

Animals↗
PubMed1983

Differential distribution of the pancreatic cancer-associated antigen (PCAA) and pancreatic tissue antigen (PaA) in pancreatic and gastrointestinal cancer tissues.

PCAA, a glycoprotein antigen fractionated from the ascites fluid of a patient with pancreatic cancer and sharing an identical immunogenicity with Gelder's POA, and PaA, a novel pancreatic tissue antigen, were studied immunohistologically. Serial paraffin sections were prepared from surgical specimens of 11 cases of pancreatic cancer, 15 of gastric cancer, 12 of colonic cancer, and 2 of gallbladder cancer; these were then subjected to immunofluorescence and immunoperoxidase stainings. In noncancerous tissues, PCAA was detected unexpectedly at goblet cells of the whole intestine, but was completely absent in pancreatic tissues, while PaA was not demonstrated in intestinal tissues, but was positive at acinar cells of the pancreas. In pancreatic cancer tissues, PCAA and PaA were detected at apical cytoplasm of cancer cells, although positive cells were in different proportions and had different distributions. PCAA-positive cells were mucin-producing (positive in PAS-alcian blue staining) and were well differentiated histologically, while PaA-positive cells were less differentiated and poor in mucin production. Among 11 cases of pancreatic cancer, both PCAA- and PaA-positive cells were demonstrated in 3 cases, PCAA-positive cells alone were found in 3 cases, and PaA-positive cells alone were seen in 4 cases. In 27 gastrointestinal cancer tissues, PCAA was detected in 7 cases of mucin-producing cancer, and PaA was demonstrated in 2 cases of poorly differentiated adenocarcinoma.

Adenocarcinoma↗
PubMed1983

Circulating antibody to prostate antigen in patients with prostatic cancer.

A reverse enzyme-linked immunosorbent assay (ELISA) modified from a prostate antigen (PA) assay previously reported has been developed to measure circulating PA-binding globulin (PABG). Serum specimens taken from normal males, normal females, male patients with nonprostatic cancers, patients with benign prostatic hypertrophy, and patients with various stages of prostate cancer were analyzed for PABG. Results revealed that only patients with an advanced stage of prostatic cancer exhibited an elevated level of PABG. PABG was then isolated from prostatic cancer patients' serum by PA affinity chromatography. Upon immunodiffusion and immunoelectrophoresis, this PABG preparation reacted with purified PA, anti-PA xenoantibodies and anti-human IgG. By the immunoperoxidase technique, PABG stained positively in prostatic ductal epithelial cells and negatively in all other tissues examined. An additional PABG preparation, which reacted with anti-PA and anti-human IgG and not with purified PA, was also isolated by an anti-PA affinity chromatography. These PABG preparations were separately subjected to high-performance liquid chromatography for further purification. Three major protein peaks at Mr of greater than 240K, 150K, and 34K were obtained. These results demonstrated that circulating IgG antibody reactive with PA was present in patients with metastatic cancer of the prostate, and this in part was in complexed form with PA and was specifically reactive with ductal epithelial elements of the prostate.

Animals↗
PubMed1983

Monoclonal antibodies (F36/22 and M7/105) to human breast carcinoma.

Cloned hybridoma cell lines were obtained from fusions of murine myeloma cells with lymphocytes of mice immunized against human breast cancer cells. Hybridomas F36/22 and M7/105 produced antibodies whose binding to breast cancer cells could not be inhibited by prior absorptions with fibroblasts, lymphoblastoid cells, or erythrocytes. Results from cell surface binding assays using a panel of tumor cell lines indicated that antibodies F36/22 and M7/105 recognized determinants expressed maximally on breast cancer cells. Antibody F36/22 reacted with normal mammary epithelial membranes and milk fat globule membranes, whereas antibody M7/105 produced no detectable binding to these specimens. Antigens carrying these epitopes each showed reactivity with concanavalin A lectin. The determinant corresponding to antibody F36/22 was detectable in histological sections of a subset of breast tumors obtained at surgery.

Adenocarcinoma↗
PubMed1983

Tissue distribution of an epithelial and tumor-associated antigen recognized by monoclonal antibody F36/22.

Murine monoclonal antibody F36/22 was derived by immunizing BALB/c mice with human breast cancer cells. This antibody reacts with an antigen located both on differentiated mammary ductal epithelia and on breast carcinomas, as examined by indirect immunoperoxidase techniques. Although the expression of this antigen correlated with estrogen receptor levels of breast tumors, antibody F36/22 did not directly react with estrophilin. In contrast to the expression of classical differentiation antigens, this antigen was found in a high percentage of poorly differentiated carcinomas of the breast. Staining intensities were similar for well- and poorly differentiated tumors; thus, antigen expression was not related to tumor grade. Intratumoral heterogeneity of antigen expression was observed in the majority of tumors. Since a subset (64 of 80) of the breast carcinomas examined have expressed the antigen, McAb 36/22 was of use for the immunological subclassification of tumors which were indistinguishable by conventional histopathological staining techniques. The antigen was also present on other adenocarcinomas (ovary, colon, stomach, pancreas, and prostate); however, these tumors usually exhibited reduced staining intensity compared with that observed in breast cancer. The normal counterpart tissues at these histotypes contained no detectable levels of the antigen, and increased expression of the antigen was associated with tumorigenesis at these sites. Tumors of mesenchymal origin and carcinomas other than adenocarcinomas exhibited undetectable levels of the antigen. Therefore, depending on the organ site, McAb F36/22 recognizes an epithelial and/or tumor-associated antigen.

Animals↗
PubMed1983

LNCaP model of human prostatic carcinoma.

The LNCaP cell line was established from a metastatic lesion of human prostatic adenocarcinoma. The LNCaP cells grow readily in vitro (up to 8 x 10(5) cells/sq cm; doubling time, 60 hr), form clones in semisolid media, are highly resistant to human fibroblast interferon, and show an aneuploid (modal number, 76 to 91) human male karyotype with several marker chromosomes. The malignant properties of LNCaP cells are maintained. Athymic nude mice develop tumors at the injection site (volume-doubling time, 86 hr). Functional differentiation is preserved; both cultures and tumor produce acid phosphatase. High-affinity specific androgen receptors are present in the cytosol and nuclear fractions of cells in culture and in tumors. Estrogen receptors are demonstrable in the cytosol. The model is hormonally responsive. In vitro, 5 alpha-dihydrotestosterone modulates cell growth and stimulates acid phosphatase production. In vivo, the frequency of tumor development and the mean time of tumor appearance are significantly different for either sex. Male mice develop tumors earlier and at a greater frequency than do females. Hormonal manipulations show that, regardless of sex, the frequency of tumor development correlates with serum androgen levels. The rate of the tumor growth, however, is independent of the gender of hormonal status of the host.

Adenocarcinoma↗
PubMed1983

Glycoprotein exhibiting immunological and enzymatic activities of human prostatic acid phosphatase.

A glycoprotein (GP) which is immunochemically and biologically related to human prostatic acid phosphatase (PAP) has been isolated from human seminal plasma by ammonium sulfate precipitation followed by sequential concanavalin A:Sepharose 4B column, anion-exchange chromatography and gel filtration. The purified GP was shown to be homogeneous by disc- and sodium dodecyl sulfate: polyacrylamide gel electrophoresis. The apparent molecular weight of purified GP was estimated to be 50,000 by gel filtration and 45,000 by sodium dodecyl sulfate: gel electrophoresis. In gel diffusion against antiserum to purified PAP, a partial immunological identity was shown between GP and PAP. This was further confirmed by an inhibition reaction between GP and antiserum to purified GP by PAP. Significantly, 30% of PAP enzyme activity was inhibited by anti-GP antiserum, while only 5% was inhibited by anti-PAP antiserum. Purified GP was shown to exhibit a weak, but significant, acid phosphatase activity by hydrolyzing alpha-naphthyl phosphate at pH 5.6. The Km and Vmax for GP are 1.6 X 10(-4) M and 0.056 mumol/min/microgram protein, respectively, using alpha-naphthyl phosphate as the substrate. In the presence of anti-PAP antibody, the enzyme activity of GP was enhanced severalfold. Furthermore, the acid phosphatase activity of GP also was inhibited by tartrate, which is the most commonly used inhibitor for PAP. GP and PAP were found to have different carbohydrate content, amino acid composition, amino-terminal sequence, and peptide map. Thus, GP represents a newly identified protein. The significance of these results at molecular and clinical levels is discussed.

Acid Phosphatase↗
PubMed1982

Carcinoembryonic antigen assay in thyroid screening.

CEA assay was incorporated into a screening program in which a high risk population for thyroid diseases due to previous irradiation for benign conditions in the head and neck areas were studied. Seven hundred eleven CEA determinations were available from 735 patients screened; 22 (3.1%) were found to have an elevated level. This is compared to 31 (1.7%) from 1875 healthy control subjects. Although the difference is statistically significant, we conclude the use of CEA assay in thyroid screening is not rewarding due to its lack of activity and specificity.

Adult↗