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Biomedical subjects

T M Chu

Publications and source records attributed to T M Chu.

At least 127 records · Page 7Linked to original sources
PubMed1981

Prostate antigen: a new potential marker for prostatic cancer.

A prostate-specific antigen, distinct from acid phosphatase, was identified by immunologic procedures in prostate tissues (normal, benign hypertrophic, and cancerous) and seminal plasma, as well as in sera of patients with prostatic cancer and of nude mice bearing human prostatic tumor. This antigen was shown by immunoperoxidase staining to be confined to epithelial cells comprising the prostatic ductal elements. Prostate antigen was purified from prostatic tissue and seminal plasma, and it was shown to have a molecular weight of 33,000-34,000 with no subunit component. The isoelectric point of purified antigen was around 6.9, though several unpurified isomers with different isoelectric points also were observed. Serum-borne prostate antigen showed a molecular weight of 90,000-100,000 but it exhibited a molecular weight of 36,000 in the presence of sodium dodecyl sulfate. A sandwich-type, peroxidase-linked immunosorbent assay capable of detecting 0.1 ng of the antigen per milliliter of blood was developed. With this technique, serum level of the antigen was found to increase in patients with prostatic cancer as compared with normal males. The prostate-specific antigen can be a useful marker for detection of prostatic cancer.

Antigens↗
PubMed1981

The use of serum isoenzymes of alkaline and acid phosphatase as possible quantitative markers of tumor load in prostate cancer.

The tumor burden of 98 patients with metastatic prostatic cancer was compared longitudinally with the activities of bone (BAP) and liver isoenzymes (LAP) of alkaline phosphatase, total acid phosphatase (AcP), and prostate-specific acid phosphatase (PAP). A quantitative association between these enzyme markers and the tumor mass was suggested by comparing the enzymes with 1) both the treatment response and the estimation of metastasis by radionuclide bone scanning; 2) metastasis based upon radiographic evidence. In addition, an apparent extensive pretreatment bone tumor load was predictive for an elevated BAP activity, which was also a suggestive poor prognosis as previously reported. An elevation of PAP, in contrast to AcP, may precede the clinical disease progression in some patients. Data presented in this report have indicated that the levels of these enzymes compared well with the extent of tumor involvement and therefore may be considered suitable as adjuvant and even quantitative biochemical markers of bone and liver metastasis.

Acid Phosphatase↗
PubMed1981

Expression of prostatic acid phosphatase in human prostate cancer.

By a specific immunochemical measurement, the activity of prostatic acid phosphatase (PAP) in prostate cancer was found to be about 25%, on average, based on micrograms DNA or per cell, of that in normal prostate or benign prostatic hypertrophy (BPH). The reduction of PAP in prostate cancer was further revealed by a decrease in PAP protein. The 125I-labeled anti-PAP IgG specifically bound to nascent peptides on PAP-synthesizing polysomes showed no qualitative differences among cancerous prostate, normal prostate and BPH. However, the quantitative binding of 125I-labeled anti-PAP IgG to polysomes of cancerous prostate was half that of normal prostate of BPH. These data suggest that a significant amount of PAP and its synthesizing polysomes was reduced in prostate cancer as a result of PAP gene suppression.

Acid Phosphatase↗
PubMed1981

Comparison of estramustine phosphate and vincristine alone or in combination for patients with advanced, hormone refractory, previously irradiated carcinoma of the prostate.

There were 121 men with hormonally refractory metastatic cancer of the prostate who were randomized to receive estramustine phosphate or vincristine, or the combination of these 2 agents. All patients had received prior radiation therapy (greater than 2,000 rad). There were 90 patients who could be compared for response. The objective response rates (partial regression or stabilization of disease) for the 3 treatment groups were 26 per cent for estramustine phosphate, 24 per cent for estramustine phosphate plus vincristine and 15 per cent for vincristine. Subjective parameters varied little among the 3 regimens. The median duration of response for those responding to estramustine phosphate was similar (20 weeks) to that for vincristine (22 weeks) and greater than that for the combination (13 weeks). The probability of survival did not differ significantly for patients randomized to each of the 3 regimens. The addition of vincristine to estramustine phosphate did not enhance the response rate achieved by estramustine phosphate alone and vincristine alone produced the lowest response rate. Estramustine phosphate continues to be the most active agent in previously irradiated patients with hormonally refractory metastatic cancer of the prostate.

Drug Therapy, Combination↗
PubMed1981

A comparison of hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea and cyclophosphamide in patients with advanced carcinoma of the prostate.

This is the fifth completed randomized clinical trial of the National Prostatic Cancer Project. There were 125 patients with histologically confirmed relapsing clinical stage D prostatic cancer randomized to receive hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on the initial therapy were crossed over or randomized to receive an alternate drug. There were 98 patients available for comparison of treatments. Objective responses included patients with complete or partial regression as well as stable disease. The response rates were 35 per cent for cyclophosphamide, 30 per cent for methyl-chloroethyl-cyclohexy-nitrosourea and 15 per cent for hydroxyurea. Subjective response parameters included improvement in performance status and relief of pain. Pain was improved in a fifth of the patients on each treatment area. Methyl-chloroethyl-cyclohexy-nitrosourea and hydroxyurea showed activity in advanced prostatic cancer patients but at the expense of excessive toxicity. Cyclophosphamide continues to be the most active single agent in this type of patient, particularly with regard to duration of response and survival. There was a statistically demonstrable advantage for cyclophosphamide over hydroxyurea and a marginal advantage over methyl-chloroethyl-cyclohexy-nitrosourea in survival experience.

Acid Phosphatase↗
PubMed1981

Biologic markers in cancer diagnosis and treatment.

We have reviewed several tumor markers that our advocates feel are now clinically useful, involve current assay technology, and are based on already available information. These include, in selected instances, estrogen receptors for breast cancer, thyrocalcitonin for medullary cancer of the thyroid, prostatic acid phosphatase for cancer of the prostate, alpha-fetoprotein for hepatocellular cancer, and carcinoembryonic antigen for monitoring colon cancer. We have considered the potential use of measurement of serum proteases and protein degradation products due to their activity as possible future areas of development, and we have explored measurement of tissue aryl hydrocarbon hydroxylase to identify populations at risk of cancer resulting from chemical carcinogenesis. It is clear that the study of tumor markers is already improving patient care in some specific areas and offers exciting potential for the future.

Acid Phosphatase↗
PubMed1981

Prostate antigen: a marker for human prostate epithelial cells.

Specificity of a previously reported prostate antigen (PA) was assessed by several immunologic procedures. This antigen, restricted in distribution to the prostate gland, was detected within ductal epithelial cells. Continuous established cell lines LNCaP and PC-3 of malignant prostate origin retained the expression of PA. Tumor cells released the antigen in vitro into the culture fluid and also in vivo into the circulation of nude mice preinoculated with LNCaP cells. Prostate cells in culture also specifically accreted immunoglobulin fragments of PA antiserum.

Animals↗
PubMed1981

Differential localization of human pancreas cancer-associated antigen and carcinoembryonic antigen in homologous pancreatic tumoral xenograft.

Tissue localization of a human pancreas cancer-associated antigen (PCAA) and carcinoembryonic antigen (CEA) was studied in a homologous pancreatic tumoral xenograft, a human pancreatic cancer line established from ascites (AsPC-1), with the use of the indirect immunofluorescence technique with specific anti-PCAA and anti-CEA antisera. Histologically, AsPC-1 xenograft was composed of mucinous adenocarcinoma of variable size and degree of glandular differentiation. PCAA was selectively associated with the columnar cytoplasm, was involved primarily in the epithelial proliferation, and originated at the basal aspect of the glands. In contrast, CEA appeared diffuse and was found predominantly in the cuboidal cells, with higher intensity at the luminal border and in mucin. Furthermore, growth comparison of the AsPC-1 adenocarcinoma revealed that, except in the juvenile gland that was morphologically consistent with grade 1 (G1) carcinoma in situ, the number of PCAA-positively stained cells decreased from G1 to grade 4 epithelial differentiation. In well-differentiated adenocarcinoma and degenerating adenocarcinoma, cells positive for PCAA were released into the lumen of the glands, whereas in poorly differentiated adenocarcinoma these cells were often scattered singly and/or in focal clusters and disappeared in very poorly differentiated adenocarcinoma. This study showed that the PCAA was different from CEA in its immunologic reactivity and distribution in its homologous tumoral tissues, in which PCAA was predominantly associated with the proliferative phase of the malignant epithelium. These results also indicated the potential applicability of this antigenic expression in the etiology, disease grading, and staging of human pancreatic cancer.

Adenocarcinoma↗
PubMed1981

Detection of a breast tissue-associated antigen by antiserum to Raji cell-bound circulating immune complexes of human breast cancer.

Rabbits tolerant to human immunoglobulin G were used to raise antisera against the Raji cell-bound circulating immune complexes from human breast cancer sera. After solid-phase adsorption treatment with glutaraldehyde-cross-linked normal human plasma, acetone-extracted normal liver tissue powder, and glutaraldehyde-fixed Raji cells, one antiserum reacted specifically with breast tissue extracts but not with extracts of other tissues, as examined by a counterimmunoelectrophoresis technique. Immunological reactivity of the treated antiserum was removed by incubation with normal, primary, or metastatic breast tumor tissue extracts. Incubation with normal human serum or extracts derived from tissues other than the breast showed no neutralizing effect on the antibodies. This specific antiserum reagent was used in a modification of the Raji cell radioimmunoassay. Raji cells were incubated with sera from cancer patients or normal controls and then reacted with 125I-labeled F(ab')2 fraction of the treated antiserum reagent. The amount of 125I-F(ab')2 bound was then determined. Although all sera exhibited elevated circulating immune complexes by the conventional Raji cell radioimmunoassay, 14 of 18 breast carcinoma sera demonstrated a significant uptake when compared with the normal population group as opposed to five (three lung and two colon) of 29 other cancer sera examined (p less than 0.001). An immunologically reactive breast tissue-associated antigen, purified from malignant breast tumor or normal breast tissue extracts with the use of antiserum reagent, exhibited an apparent molecular weight of 85,000 by sodium dodecyl sulfate; polyacrylamide gel electrophoresis and a pI value of 4.9 +/- 0.2. These results demonstrated that a breast tissue-associated antigen rather than a breast tumor-associated neoantigen, was involved in circulating immune complexes of breast cancer patients as detected by Raji cell immunoassay. It also implied the occurrence of disease-related autoimmunity in human breast cancer.

Antigen-Antibody Complex↗
PubMed1981

Use of human prostate-specific antigen in monitoring prostate cancer.

The newly reported human prostate-specific antigen (PA) is a specific histiotypic product of human prostate. With the use of a sensitive enzyme immunoassay, the circulating PA in prostatic cancer patients has been evaluated clinically. In 96 patients with advanced stage of disease (D2) and receiving chemotherapies, the pretreatment serum PA levels were found to be of prognostic value with regard to the patient survival. Ten patients with metastatic prostate cancer were monitored for more than 32 weeks by 183 serial PA values and were found generally to respond to the treatment. Additionally, in another group of 32 patients who underwent curative therapies for localized prostate cancer, 161 serum samples were evaluated during periods of 12 to 114 weeks (average 56 weeks). Of these patients, five developed metastases during follow-up, and all were shown to exhibit increasingly elevated PA values, either corresponding to or preceding the clinical diagnosis of disease recurrence. These results suggest that PA is a new marker with potential value to merit further clinical study.

Antigens, Neoplasm↗
PubMed1981

Recovery of immunologically reactive antibodies and antigens from breast cancer immune complexes by preparative isoelectric focusing.

A new technique for the recovery of immunologically reactive antibodies and putative antigens from breast cancer-associated immune complexes was described. Soluble immune complexes were isolated from extracellular fluids by 2.5% polyethylene glycol fractionation and affinity chromatography on Protein A:Sepharose CL-4B. The immune complexes bound to immobilized Protein A were then subjected to preparative isoelectric focusing. The dissociated immunoglobulins and putative antigens were recovered from the appropriate pH regions of the preparative isoelectric focusing gel. G-type immunoglobulins recovered from immune complexes isolated from a breast cancer patient bound to the recovered putative antigen(s) and three breast cancer cell culture lines, but these immunoglobulins did not bind to carcinoembryonic antigen or other cancer cell culture lines originating in colon, pancreas, prostate, or lymphoblast. The recovered putative antigens had isoelectric points between pH 3.0 and 5.0 and molecular weights of 20,000 and 42,000.

Antibodies, Neoplasm↗
PubMed1980

A solid-phase immunoadsorbent assay for serum prostatic acid phosphatase.

A solid-phase immunoadsorbent assay for serum prostatic acid phosphatase (PAP) measurement has been developed as modified from our previously reported immunofluoroassay, utilizing the specific anti-PAP antibodies conjugated to CNBr-activated Sepharose 4B. The serum prostatic acid phosphatase was bound, and separated from other acid phosphatases and serum proteins, by the solid-phase anti-PAP IgG Sepharose 4B. The enzyme activity was quantitated by measuring the enzyme hydrolytic product, alpha-naphthol, from a primary standard solution. The entire procedure could be performed within four hours. The sensitivity of this method was 0.22 I.U./l of enzyme activity or 0.88 ng of prostatic acic phosphatase protein per ml of serum. Normal range of serum prostatic acid phosphatase as determined by this assay was found to be 0.4--2.4 I.U./l of enzyme activity (or 1.60--9.60 ng of enzyme protein per ml of serum). Initial clinical evaluation showed that 19 of 25 patients with early stages of prostatic cancer and 12 of 14 patients with metastatic prostatic cancer exhibited an elevated enzyme level (overall 79%), as compared with only six and eight patients, respectively (overall 36%), by a conventional chemical method.

Acid Phosphatase↗
PubMed1980

Tumor antigens as related to pancreatic cancer.

Data are presented suggesting the presence of pancreas tumor-associated antigens. Slow progress has been made during the past few years in the identification of pancreatic tumor antigens that may be of clinical usefulness and it seems unlikely that many of the practical problems now being faced in identification and isolation of these antigens and in development of a specific, sensitive assay will be solved by conventional immunochemical approaches. The study of antigen and/or antibody purified from immune complexes in the host and the application of leukocyte adherence inhibition techniques to immunodiagnosis of pancreatic cancer are among the new approaches that may provide effective alternatives in the study of pancreatic tumor antigens.

Antigen-Antibody Complex↗
PubMed1980

An assessment of bone scans for monitoring osseous metastases in patients being treated for prostate carcinoma.

The National Prostatic Cancer Project held a workshop in March 1980 to examine procedures used to evaluate bone metastases. Variations in techniques used by each of 9 treatment centers, as well as the National Cancer Institute, were compared. One center in particular had developed procedures for quantitating bone scans in addition to the customary qualitative evaluation. Changes in bone scan assessments were also related to changing levels of isoenzymes of acid and alkaline phosphatase. Most consistently correlated with disease changes were prostatic acid phosphatase, as determined by counter-immunoelectrophoresis, and the isoenzyme of bone alkaline phosphatase. Gamma cameras were recommended over rectilnear scanners as were multiple spot films to concentrate on problem areas. Bone scans must be performed prior to therapy and for best assessment no sooner than 3 months to avoid the flair phenomenon. Consistency of both machine settings and patient position are paramount, as are quality of equipment and review of past scans and X-ray films where appropriate to obtain the best assessment of disease status.

Bone Neoplasms↗
PubMed1980

Fundamental biochemical and immunological aspects of prostatic acid phosphatase.

Prostatic acid phosphatase (PAP) was purified from human malignant prostate tissue by means of ammonium sulfate fractionation followed by sequential chromatographies of ion exchange, affinity column, and gel filtration. PAP has a molecular weight of 100,000 and consists of two subunits of 50,000. Owing, in part, to sialic acid contents in the molecule, PAP has multiple isoelectric points (pIs) at 4.2-5.5. In 0.2 M citrate, PAP has the highest affinity (Km 9.2 x 10(-5) M) in hydrolyzing alpha-naphthyl phosphate among the phosphomonoesters. Tartrate and heat at 37 degrees C for 2 hours almost completely inhibit PAP enzymic activity. By immunoprecipitate technique, anti-PAP heteroantiserum exhibited a distinct immunologic characteristics. Further, PAP possessed different antibody-binding site from enzyme hydrolytic site.

Acid Phosphatase↗
PubMed1980

Isoelectric focusing--a new approach to the study of immune complexes.

Isoelectric focusing was used to examine antigen-antibody complexes. BSA : anti-BSA complexes were dissociated and antigen was separated from antibody based upon differences in pI value by isoelectric focusing (pH gradient 3--10). The recovered proteins were homogeneous as determined by immunodiffusion and polyacrylamide gel electrophoresis analyses. The technique was capable of resolving 6.4 microgram of BSA : anti-BSA complexes. More than 90% of the complexes applied to isoelectric focusing gels were dissociated and entered the gels. It was further demonstrated, by the use of complexes containing enzymes (acid phosphatase or alkaline phosphatase), that the dissociated enzymes retained their native pI as well as enzymatic activities. The isoelectric focusing technique, therefore, represents a new and effective approach to the dissociation of antigen-antibody complexes.

Animals↗