Search PubMed⌕ Search

Biomedical subjects

T M Chu

Publications and source records attributed to T M Chu.

At least 73 records · Page 4Linked to original sources
PubMed1986

What's new in tumor markers for prostate cancer?

The clinical features of a new prostate tumor marker, prostate-specific antigen (prostate antigen, PA), has been reviewed. Although PA cannot be used in early detection of prostate cancer, simultaneous determination of PA and PAP yields an additive clinical value in immuno-diagnosis of prostate cancer. At the present stage of development, PA is most useful as a prognostic marker for monitoring disease recurrence and treatment response. Also, PA is an effective immunohistologic marker for differential diagnosis of metastatic carcinomas with unknown primary, especially in the identification of metastatic prostate tumor in distant metastases and in the differentiation of primary prostate carcinoma from poorly differentiated transitional cell carcinoma of the bladder. Unequivocal evidence is not yet available on the role of circulating PA-binding globulin as an auto-antibody or an anti-tumor antibody as a result of patient's immune response. This observation is of clinical value for investigation of prostate cancer biology. The intriguing protease activity as detected in PA may provide new avenues for prostate cancer research.

Acid Phosphatase↗
PubMed1986

Characterization of a new primary human pancreatic tumor line.

A primary human pancreatic tumor line (BxPC-3) has been established from a biopsy specimen of a histologically confirmed adenocarcinoma of the body of the pancreas. Tumorigenicity was proven by xenograft in athymic nude mice. Upon re-establishment of tumor xenografts in tissue culture, the epithelial tumor cells retained their original morphology. Histopathologically, the tumors grown in nude mice exhibited the original characteristics of the primary adenocarcinoma in the patient, producing traceable mucin and displaying moderately well to poorly differentiated adenocarcinomas with occasional lymphocytic infiltrations at the tumor peripheries. Furthermore, the tumor xenografts differentially expressed carcinoembryonic antigen, human pancreas cancer-associated antigen, and human pancreas-specific antigen. Karyotyping and glucose-6-phosphate dehydrogenase isoenzyme characterization revealed that this tumor line was of human origin and devoid of HeLa cell contamination. The BxPC-3 tumor line has been maintained for more than four years in our laboratory and represents a valuable model for primary human pancreatic cancer.

Adenocarcinoma↗
PubMed1986

Relative reliability of five serially measured markers for prognosis of progression in prostate cancer.

During an 8-year period, 1,065 serum specimens were collected from 79 patients with prostate cancer of stages B2 to D1 (group I) and 51 patients with newly diagnosed stage D2 prostate cancer (group II) to evaluate statistically the relative reliability of elevated tumor-associated markers for progressive disease in prostate cancer. Forty of the group I patients and 21 of the group II patients presented a clinical progression of disease during follow-up. With the use of Gail's modification of Cox's regression model, serial acid phosphatase (AcP), total alkaline phosphatase (TAP), bone alkaline phosphatase (BAP), prostatic acid phosphatase (PAP), and prostate-specific antigen (PA) were analyzed. Results from group I patients revealed that only PA (P = .0002) and PAP (P = .0684) were prognostically important markers for detection of imminent disease progression. However, all markers were prognostically important in group II patients. Comparative studies indicated that PA (P = .0052) and PAP (P = .0359) were the more reliable markers for group I patients, whereas PA (P less than .0001), BAP (P = .0007), and PAP (P = .0206) were the more reliable markers for group II patients. Multivariate analyses revealed that, after adjustment for the effect of PA, no other marker was significantly related to the risk of progression. Elevated PA levels were predictive of increased risk 6 months before disease progression in group I patients only (P less than .0001). Overall, the apparent order of prognostic reliability for disease progression was found to be PA greater than PAP greater than BAP greater than AcP greater than TAP.

Acid Phosphatase↗
PubMed1986

Effect of methotrexate-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor.

Methotrexate (MTX) was conjugated to an immunoglobulin G1 (IgG1) monoclonal antibody specific for human prostatic acid phosphatase (PAP) by the active ester method. The molar ratio of MTX to IgG was 14. MTX-monoclonal antibody conjugate retained substantially the original PAP-binding inhibition activity of the monoclonal antibody. Both MTX-monoclonal antibody conjugate and an identically prepared MTX-normal mouse IgG conjugate preserved 90% of the original dihydrofolate reductase inhibitory activity of MTX. [3H]MTX conjugated to monoclonal anti-PAP antibody was significantly accumulated more in PAP-producing human prostate tumor LNCaP cells than its normal mouse IgG counterpart. No statistical difference was found between the uptake of [3H]MTX conjugated to monoclonal antibody and that of [3H]MTX conjugated to normal mouse IgG by control PAP nonproducing thyroid tumor cells (TT). The antitumor effect of the conjugate was evaluated in vitro by its inhibition on deoxy[6-3H]uridine incorporation into LNCaP cells. The inhibition by MTX-monoclonal antibody conjugate was significantly higher than that by MTX-normal mouse IgG conjugate at 8 micrograms of drug per ml, although it was significantly less than that by free MTX. However, an in vivo tumor and tissue distribution study of [3H]MTX and its conjugates revealed that, 5 days after i.v. administration, [3H]MTX conjugated to monoclonal antibody was preferentially accumulated in LNCaP prostate tumor. Tumor:blood ratios for [3H]MTX, [3H]MTX-monoclonal antibody conjugate, and [3H]MTX-normal mouse IgG conjugate were 1.47, 5.06, and 1.26, respectively. Preliminary results obtained from a pilot study with a small number of animals demonstrated that multiply injected MTX-monoclonal antibody conjugate retarded the growth of xenografted prostate tumor (LNCaP) as compared with the control groups, including free MTX which showed a shorter period of therapeutic effectiveness. This study suggests that MTX conjugated to monoclonal anti-PAP antibody could be a potential reagent for experimental immunochemotherapy of prostate tumor, should the initial in vivo data be extended and confirmed.

Acid Phosphatase↗
PubMed1985

Prognostic importance of prostate-specific antigen for monitoring patients with stages B2 to D1 prostate cancer.

To evaluate the prognostic value of prostate-specific antigen (PA) for detection of tumor growth after definitive therapy, 602 sera from 70 patients with stages B2 to D1 prostate cancer (26 of whom recurred) were analyzed in a blind study. Using Cox's proportional-hazards model, a highly significant association was found between serially measured PA and disease-free survival time (p = 0.0002). A positive predictive value of 100% was found for some markedly elevated PA levels and confirmed recurrence of disease. In fact, this study suggested that once a PA level of 88 ng/ml was reached, there was an average time of less than 2 months before a recurrence was clinically confirmed. Tumor growth in patients who recurred was indicated by a PA elevation before recurrence in 92% (24 of 26) as opposed to 20% (9 of 44) in disease-free patients. Additionally, in these 24 of 26 patients, levels of PA were elevated 12 months (mean lead time) before a confirmed disease recurrence. In patients who were still disease free, serial PA appeared to increase concurrently with putative tumor growth as shown by the initial surgical stage. Generally, the greater the PA level the more advanced was the stage of disease (B2 to D1). These data suggest that PA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined prostate cancer.

Antigens, Neoplasm↗
PubMed1985

Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (AsPC-1) implanted orthotopically into nude mice.

An orthotopic xenograft of the human pancreatic tumor was established by inoculating human pancreatic tumor AsPC-1 cells into the duodenal lobe of the pancreas of the athymic nude mouse. Microscopically, the xenograft was formed by a heterogeneous population of tumor cells, displaying moderately to poorly differentiated adenocarcinomas with the latter capable of invading the adjacent pancreatic islets or non-endocrine elements. At 4 weeks post-transplantation, the tumor was detectable as a focal implant at the site of inoculation and thereafter grew progressively leading to extensive visceral invasion and metastasis. In contrast to the subcutaneous xenograft, all the mice (9/9) bearing orthotopically transplanted tumor developed secondary foci in the gut and at the peritoneum, with 7, 6, and 4 animals showing additional kidney, mesenteric lymphnodal, and diaphragm metastases, respectively. Distant metastases in the lungs were found in 3 mice and malignant ascites developed in two. Human pancreas cancer associated antigen was detected in the tumor, serum, and ascitic fluid of the mice at 63 +/- 24 micrograms/gm, 15 +/- 6 micrograms/ml, and 5 micrograms/ml, respectively. The finding of these regional and distant metastases was quite different from that in the animal bearing subcutaneously xenografted tumor where no metastases to internal organs was observed. The results suggest the potential use of this experimental system in tumor biology and antigen expression of human pancreatic cancer in vivo.

Animals↗
PubMed1984

Immunologically reactive tryptic fragments of human prostatic acid phosphatase.

Three peptide fragments (designated II, III and IV) of human prostatic acid phosphatase (PAP) were isolated to homogeneity from a limited tryptic hydrolysate of PAP by gel filtration on Sephadex G-100, followed by chromatography on DEAE-cellulose and Sephadex G-75. The homogeneity was confirmed by disc poly-acrylamide-gel electrophoresis. The Mr values were 32 500, 25 000 and 11 000 as estimated by gel filtration and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Immunoprecipitation study revealed that only fragment II formed an immune precipitate with anti-PAP antibodies. Fragment II exhibited 45% of maximum inhibitory activity on the reaction between PAP and goat anti-PAP IgG (immunoglobulin G) antibodies (or rabbit anti-PAP antibodies), whereas fragments III and IV demonstrated 24% (or 23%) and 29% (or 27%) inhibition respectively. A mixture of these three tryptic fragments of PAP result in 96% (for goat anti-PAP antibodies) and 94% (for rabbit anti-PAP antibodies) inhibitory activities, which were equivalent to the sum of maximum inhibitory activity of the three fragments individually. The results demonstrated that these three tryptic peptide fragments carried all the antigenic active sites of the native PAP, and suggested that the entire molecule of human PAP comprised a minimum of four distinguishable, nonoverlapping antigenic determinants. These three fragments also were shown to retain all the disulphide bonds of the native PAP, and thus were useful reagents for the elucidation of PAP molecular structure.

Acid Phosphatase↗
PubMed1984

The proteolytic activity of human prostate-specific antigen.

Human prostate-specific antigen has been found to exhibit a mild activity of protease at neutral pH. This finding is based on two observations: a proteolytic activity was always associated with the antigen fractions during purification, and the proteolytic activity and the antigen were precipitated with specific antibody to the antigen. In comparison with physico-chemical and catalytic properties of known proteases, human prostate-specific antigen is a distinct neutral protease.

Amino Acid Sequence↗
PubMed1984

Immunoaffinity isolation of ductal carcinoma antigen using monoclonal antibody F36/22.

Monoclonal antibody (McAb) F36/22, raised against a human breast tumor line, identifies an antigen found in the circulation of cancer patients. Antigen was purified from malignant effusions using McAb-affinity chromatography followed by adsorption-desorption from immobilized wheat germ lectin. Electrophoretic analysis demonstrated the isolation of a single high mol. wt glycoprotein exhibiting an isoionic point near pH 4.2 and a density of approx. 1.45 g/ml. Although highly reactive with wheat germ lectin, a negligible or weak interaction was observed with concanavalin A, lentil and peanut agglutinin. The antigen was immune-precipitable, indicating the occurrence of multiple McAb-binding sites, and was resistant to heat and acid treatments. Antigenicity was not perturbed following protease or neuraminidase treatments, but was affected upon exposure to alkaline conditions. Taken together, these data suggest that McAb F36/22 recognizes a high mol. wt component occurring in circulation as a mucin-like glycoprotein.

Antibodies, Monoclonal↗
PubMed1984

Expression of ductal carcinoma antigen in breast cancer sera as defined using monoclonal antibody F36/22.

A quantitative immunoassay procedure has been constructed to evaluate levels of ductal carcinoma antigen recognized by murine McAb F36/22. Using this method, 3% of 64 apparently healthy individuals and 13% of 40 patients with benign breast disease expressed serum antigen levels above 70 units/ml. Greater than 50% of 116 patients with clinical evidence of breast cancer demonstrated circulating ductal carcinoma antigen levels above 70 units/ml. Patients with ductal carcinomas of other sites, including prostate and gastrointestinal tumors, also demonstrated elevated levels of antigen (11 and 27%, respectively). The incidence of elevated serum ductal carcinoma antigen levels correlated significantly with the incidence of intratumoral antigen expression. Lectin binding, molecular weight, and density measurements indicated that circulating antigen occurs as a high-molecular-weight glycoprotein with mucin-like characteristics.

Antibodies, Monoclonal↗
PubMed1984

Immunologic markers and the diagnosis of prostatic cancer.

The authors review recent developments in the immunodiagnosis of prostatic cancer. Monoclonal antibodies to prostatic acid phosphatase, prostate-specific antigen, and several human prostate and prostate-cancer-related components are available. Prostatic acid phosphatase and prostatic antigen assays are still the only immunologic tools with clinical applications.

Acid Phosphatase↗
PubMed1984

Reactivity of monoclonal antibody F36/22 with human ovarian adenocarcinomas.

Monoclonal antibody F36/22 recognizes high-molecular-weight glycoprotein components associated with neoplastic development of the ovary. Indirect immunoperoxidase staining techniques were performed on a panel of nonmalignant ovarian tissues, primary ovarian tumors, exfoliated ascitic tumor cells, and metastatic lesions. Normal ovarian tissue components (n = 20) failed to exhibit detectable levels of antigen, whereas benign ovarian tissues show a low incidence of immunostaining (three of 26) restricted to some ductal elements. One hundred % (19 of 19) of the immunopositive primary malignant tumors were histologically classified as adenocarcinomas. Each of the predominant adenocarcinoma histotypes consistently showed expression of the antigen with 30 to 100% of the tumor cells scored as immunopositive. Ascitic tumor cells obtained from all of the ovarian adenocarcinoma patients examined (47 of 47) displayed immunopositive reactions, whereas normal mesothelial cells in these specimens exhibited undetectable staining. In addition, ovarian adenocarcinoma metastases (12 of 12) exhibited very intense immunoreaction products. No detectable antigen was expressed by nonadenocarcinoma ovarian tumor cells.

Adenocarcinoma↗
PubMed1984

Relationship between antigen density and immunotherapeutic response elicited by monoclonal antibodies against solid tumors.

The relationship between the level of cell surface antigen expression and solid tumor immunotherapy with monoclonal antibody (MoAb) was evaluated. Two MoAb's that were shown effective in the passive therapy of breast carcinomas of human origin, established and growing in female Swiss nude mice, were used for these studies. Several groups of tumors were produced from cell cultures of different passages; each cell culture possessed a distinct target antigen level. Results from immunotherapy experiments demonstrated that the amount of tumor reduction response after MoAb therapy was proportional to the antigen density at the cell surface. Analysis of these data indicated a theoretical improbability of a single MoAb treatment being able to completely eradicate solid tumors and may necessitate the use of multiple MoAb's to circumvent this problem.

Animals↗