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Biomedical subjects

T M Chu

Publications and source records attributed to T M Chu.

At least 145 records · Page 8Linked to original sources

Value of new fluorescent immunoassay for human prostatic acid phosphatase in prostate cancer.

A new solid phase fluorescent immunoassay for human prostatic acid phosphatase in prostatic cancer has been evaluated. This technique is rapid, quantitative, and sensitive. In more than 133 patients studied by the National Prostatic Cancer Project, positive results were obtained in patients with localized, nonmetastatic disease as confirmed by clinical testing, surgical staging, and careful inspection of all pelvi lymph node material in appropriate cases. That this can occur even in Stage A2 patients may alter current concepts on the staging or, even further, on the therapy of prostatic cancer.

Acid Phosphatase↗

Prostatic origin of tumors. An immunohistochemical study.

An immunoperoxidase technic was used to localize prostatic acid phosphatase in a variety of primary and metastatic neoplasms. The aim was to explore the histogenesis of tumors affecting the prostate gland and to demonstrate the prostatic origin of metastases in various sites. A highly specific antiserum to prostatic acid phosphatase was raised in rabbits, and the peroxidase-antiperoxidase procedure was carried out on formalin-fixed paraffin-embedded routine pathology material. All specimens from the 37 cases of known primary and metastatic prostatic carcinomas stained positively for prostatic acid phosphatase, regardless of their histologic differentiation. None of the specimens from the 44 cases of proven nonprostatic primary and metastatic tumors stained positively for prostatic specific acid phosphatase. The data suggest that demonstration of prostatic acid phosphatase by the immunoperoxidase technic is a practical, sensitive, and specific test for the prostatic origin of an otherwise unclassifiable primary or metastatic neoplasm.

Acid Phosphatase↗

Measurements of prolactin and androgens in patients with prostatic diseases.

Testosterone (T), dihydrostestosterone (DHT) and prolactin (HPr) levels were determined in normal males and females, in patients with benign prostatic hypertrophy (BPH) and in clinically stable patients with prostatic carcinoma (CAP), intact and orchiectomized. CAP patients were either untreated or on different modalities of therapy. The HPr levels were higher in prostatic cancer patients, in BPH patients, and in subjects on estrogen therapy. No significant differences were found between controls or patients treated with 5-Fu plus cytoxan. The T and DHT levels were decreased in all noncontrol subjects. The levels of DHT in intact, untreated CAP patients or those receiving 5-FU plus cytoxan were significantly higher than in BPH patients. Based on these observations, it appears that HPr could be involved with T and DHT in a feedback control role, especially in BPH. The alterations in these hormone levels in CAP treated or untreated patients are in marked contrast and must be evaluated further.

Adult↗

Quantitation of prostate-specific antigen in serum by a sensitive enzyme immunoassay.

A sensitive sandwich-type enzyme immunoassay has been developed for quantitation of a human prostate-specific antigen (PA). With this method, PA at a concentration as low as 0.10 ng/ml can be detected. The assay was reproducible as within and between assays yielded a coefficient of variation of 5.7% and 4.6%, respectively. Only human prostate tissues (n = 31) were shown to contain PA. No PA was detected in other human normal or tumor tissues (n = 13). PA was not detectable in sera from normal females (n = 17) or female cancer patients (n = 25). A mean +/- S.D. of 0.47 +/- 0.661 ng/ml (ranging from less than 0.10 to 2.6) ws obtained from a group of 51 normal males. Sera from male patients with nonprostatic cancer contained a similar range of PA as that of normal males. Patients with prostate cancer (371 of 442) and benign prostatic hypertrophy (13 of 19) were shown to have elevated levels of circulating PA. Although no quantitative difference in PA levels was found between the benign prostatic hypertrophy group and Stage A of prostatic cancer, patients with Stages C and D prostatic cancer exhibited significantly elevated levels of PA qualitatively and quantitatively. These results therefore indicate that PA is a histiotypic product of the prostate and may be of use as an adjunctive tool in diagnostic procedures of prostate cancer.

Antigens↗

Modern concepts of acid and alkaline phosphatase measurement.

Three new assay methods for prostatic acid phosphatase are described relative to results of biochemical methods. Methods for total and isozymes of alkaline phosphatase are also described. Results of a field trial for acid phosphatase tests among multiple institutions in the United States revealed a marked increase in sensitivity for one assay (CIEP) over biochemical methods. which was positive with increasing frequency as the clinical and surgical stage advanced beyond B. Only for stage D did the biochemical method approach the sensitivity of the CIEP assay. The CIEP assay has potential value as a screen for prostate cancer. Another acid phosphatase assay (RIA) proved difficult to perform for many institutions in the field trial. A new solid phase immunofluorescent assay recently introduced may on further testing be more sensitive than the CIEP assay. Total alkaline phosphatase levels studied in patients with advanced disease were markedly elevated in over one-third of the cases. Higher levels were associated with poor survival or response to chemotherapy. Alkaline phosphatase isozyme levels were of added value in locating the site of the increased alkaline phosphatase activity in soft tissue, bone, or liver. Occasionally in the face of a normal total value, increased isozyme activity in one of the aforementioned compartments preceded clinical ability to detect the metastatic foci.

Acid Phosphatase↗

Isolation of prostatic acid phosphatase-binding immunoglobulin G from human sera and its potential for use as a tumor-localizing reagent.

A human immunoglobulin that binds prostatic acid phosphatases (PAP) was isolated from the serum of normal individuals by affinity chromatography using a PAP-Sepharose solid adsorbent. The yield of isolated protein, termed PAP-binding globulin (PAPBG), ranged from 4.7 to 16.3 microgram/ml serum. As shown by immunoelectrophoresis, PAPBG is a gamma-globin of restricted electrophoretic heterogeneity. PAPBG was shown to bind radiolabeled PAP by radioimmune precipitation, and an association constant of 5.0 x 10(4) M-1 was calculated. As determined by immunofluorescence, PAPBG was shown to react with human prostatic tumor cell lines. No binding was detected to other tumor cells examined including those from cultures of human breast, thyroid, pancreas, or normal fibroblasts.

Acid Phosphatase↗

Purification and characterization of acid phosphatase from Dunning R3327H prostatic adenocarcinoma.

Acid phosphatase (phosphoric monoester hydrolase) was isolated from the Dunning R3327H prostatic adenocarcinoma, a slow-growing and hormone-sensitive rat prostate tumor histologically similar to well-differentiated human prostatic cancer. The enzyme was purified to homogeneity and characterized. In comparison with the acid phosphatase isolated from human malignant prostate, the acid phosphatase from the Dunning rat tumor was similar in molecular weight [100,000 +/- 10% (S.D.)]. However, it possessed a single isoelectric point of 7.6 (human prostatic acid phosphatase showed multiple isoenzymes at 4.4 to 5.3); an electrophoretic mobility of 0.5 in reference to human prostatic acid phosphatase on 7.5% polyacrylamide gel, pH 8.5; an optimal pH of 5.0 with alpha-naphthyl phosphate as the substrate in 0.1 M citrate buffer (human prostatic acid phosphatase, 5.5); and a Km (alpha-naphthyl phosphate) of 6.9 X 10(-4) M (human prostatic acid phosphatase, 4.4 X 10(-5) M). Furthermore, it did not cross-react with antiserum raised against human prostatic acid phosphatase. These results show that the acid phosphatase of the Dunning R3327H prostatic adenocarcinoma is biochemically and immunologically distinct from human prostatic acid phosphatase and may be unique for this animal model of prostatic cancer.

Acid Phosphatase↗

A prostate antigen in sera of prostatic cancer patients.

A prostate antigen has been detected by a rocket immunoelectrophoresis technique in 17 of 219 sera obtained from patients with advanced prostatic cancer. Sera from 175 patients with nonprostatic cancers, including those with late-stage disease of the breast, lung, colon, rectum, stomach, and pancreas, were antigen negative as were 20 samples each from normal adults and age-matched males. Antigen in sera showed immunological identity with antigen in prostate tissue as determined by immunoprecipitation peak enhancement experiments. Using antibody affinity chromatography and radioimmunoprecipitation techniques, the antigen in sera was purified and subjected to sodium dodecyl sulfate electrophoresis; it exhibited a molecular weight of approximately 36,000, similar to that of antigen isolated from prostatic tissue.

Acid Phosphatase↗

Quantitative counterimmunoelectrophoresis assay for prostatic acid phosphatase.

We developed two quantitative counterimmunoelectrophoretic (CIEP) assays to detect serum prostatic acid phosphatase (PAP). The assays were designated counterimmunoelectrophoresis-colorimetric (CIE-C) and counterimmunoelectrophoresis-densitometric (CIE-D). One unique feature of these assays was the use of a primary standard for the quantitation of PAP. The sensitivities of the assays were 0.08 and 0.04 IU per liter for CIE-C and CIE-D, respectively. Precision coefficients of variation and recovery studies for four levels of PAP over a 3-month period have shown the reliability of these newly modified assays. PAP activity in sera from patients with early stages of prostatic cancer which was demonstrated to be normal by conventional chemical methods was found to be elevated by the conbined methods in a substantial number.

Acid Phosphatase↗

Selectivity of the micro-leukocyte adherence inhibition assay in pancreatic cancer.

A modified leukocyte adherence inhibition assay was performed on white blood cells from patients with ductal pancreatic cancer, other malignancies, benign gastrointestinal diseases including pancreatitis, and healthy controls, using four different ductal pancreatic cancer membrane preparations and similar preparations from gastric and colorectal cancers. A mean adherence index of less than or equal to 0.2 was evidence that the leukocytes "recognized" the antigen(s). In 9 of 10 patients with localized pancreatic cancer, 13 of 15 leukocyte populations "recognized" the pancreatic cancer antigen(s) and not other tested antigen(s). Leukocytes from only 11 of 18 patients (17 of 29 assays) with metastatic pancreatic cancer "recognized" the pancreatic tumor antigen (and no other antigen). The inability to recognize the pancreatic tumor antigen(s) was not related to nutritional, biochemical or therapeutic status of the patient, but was related to the demonstration of a response to skin test antigens. In contrast, 3 of 35 leukocyte populations in 2 of 31 patients with malignancies other than pancreatic, 1 of 28 with benign gastrointestinal disease, and one of 38 healthy control populations "recognized" the antigen. The LAI is worthy of further study in the differential diagnosis of pancreatic cancer.

Adenocarcinoma↗

The value of carcinoembryonic antigen in patients with carcinoma of the lung.

Carcinoembryonic antigen levels in 682 lung cancer patients have been studied in order to assess their value in the screening of high-risk populations, monitoring total surgical ablation and projecting the effectiveness of therapy. The initial values are shown to be related to the histology of the tumor and to the extent of the disease. All histologic types of lung cancer produce elevated CEA but adenocarcinoma characteristically produces higher values than small, large or squamous cell carcinomas. CEA has its most precise value in distinguishing at an early date cured patients subsequent to surgical resection from those patients who will eventually fail because of recurrent disease.

Adenocarcinoma↗

Immune complexes in breast cancer patients as detected by C1q binding.

Levels of Clq binding activity have been measured in the sera of patients with benign and malignant breast disease. Cancer patients showed significantly higher binding activity than patients with gross fibrocystic disease. Clq binding levels were not related to levels of carcinoembryonic antigen, or rheumatoid factor. The Clq reactive material was identified as being precipitable with Protein A, and predominantly eluted in gel filtration fractions with a molecular weight of approximately 1 x 10(6). These studies indicate that Clq binding level may be of use in the differential diagnosis of benign and malignant breast disease.

Antibodies, Neoplasm↗

Two new, direct, and specific methods of acid phosphatase determination. National field trial.

A national study of the new specific assays for prostatic acid phosphatase was conducted by the National Prostatic Cancer Project. The results of the study have confirmed that the counterimmunoelectrophoretic method is easily reproducible, highly specific, and sufficiently sensitive. Based on tests as performed by different institutions, the counterimmunoelectrophoretic (CIEP) method was also shown to have high reproducibility and was found to be of much greater sensitivity than the conventional biochemical methods for the detection of earlier stages of prostatic cancer. The national study of the radioimmunoassay (RIA) has shown that although being a highly sensitive method, it could not be readily distributed at this time from one specialized center. It requires highly specific, expensive technical assistance and is not yet available nationwide. CIEP is recommended at this time to be used as the preferred method in the evaluation and diagnosis of prostatic cancer. The value of counterimmunoelectrophoresis in detecting early prostatic cancer as a screening method is promising, but still under study.

Acid Phosphatase↗

Comparison of procarbazine, imidazole-carboxamide and cyclophosphamide in relapsing patients with advanced carcinoma of the prostate.

In this third cooperative chemotherapy trial of the National Prostatic Cancer Project 165 patients with histologically confirmed, relapsing clinical stage D prostatic cancer were randomized to receive either imidazole-carboxamide, procarbazine or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on initial therapy were crossed over or randomized to receive an alternate drug. There were 129 patients available for comparison of treatments. The objective response rates (partial regression plus stable disease) were 26% for cyclophosphamide, 27% for imidazole-carboxamide and 14% for procarbazine. Subjective responses were noted in pain relief, improvement in performance status and weight gain. Procarbazine was associated with excessive toxicity, resulting in many patients (28%) discontinuing therapy within the first 3 weeks and closure of this particular arm of the study. The regimen of initial imidazole-carboxamide therapy with a later cross-over to cyclophosphamide when the disease continues to progress is associated with the longest increase in survival. Imidazole-carboxamide and cyclophosphamide appear to be active agents in advanced prostatic cancer and are worthy of continued use in this disease.

Aged↗

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9% of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Chlorambucil↗