Search PubMed⌕ Search

Biomedical subjects

T M Chu

Publications and source records attributed to T M Chu.

At least 109 records · Page 6Linked to original sources
PubMed1982

Human pancreatic adenocarcinoma: in vitro and in vivo morphology of a new tumor line established from ascites.

A human pancreatic tumor cell line has been established from the ascites of a patient with histopathologically confirmed adenocarcinoma of the head of the pancreas and maintained for more than 12 months in the laboratory. Epithelioid tumor cell colonies, which resulted from primary tissue cultures of the ascitic cell component, were mechanically isolated by needle micromanipulation. Tumorigenicity was proven in athymic nude mice. Morphologically the pancreatic tumor epithelial cells grew to confluency with moderately tight adhesion to the culture plastic surface and with free-floating cells in the medium. Upon re-establishment of the tumoral xenograft in tissue culture, the epithelial cells retained their original morphology. Histologically the tumor grown in nude mice exhibited prototypic characteristics of the primary adenocarcinoma in the patient, producing abundant mucin and displaying a broad spectrum of glandular differentiation, which ranged from well to poorly differentiated adenocarcinomas with occasionally localized lymphocytic infiltrations. Furthermore, the tumor expressed carcinoembryonic antigen and human pancreas cancer associated antigen. This tumor line, designated AsPC-1, has been cultured for at least 10 passages in vitro and 3 in vivo. It represents a new model for human pancreatic cancer.

Adenocarcinoma↗
PubMed1982

Serum prostatic antigen measurement in localized prostatic cancer: correlation with clinical course.

Serial serum prostatic antigen measurements were performed on patients treated for localized prostatic carcinoma. There was good correlation of mean serum prostatic antigen levels and the surgical stage of the disease. Among patients treated by radical prostatectomy there was good correlation of an elevated serum prostatic antigen and the development of metastatic disease. It appears that serum prostatic antigen is a good indicator and predictor of the development of distant metastasis in this group of patients.

Aged↗
PubMed1982

Placenta-like isoenzyme of alkaline phosphatase in prostatic cancer.

Assays for serum placenta-like (Regan) isoenzyme of alkaline phosphatase were done on 157 samples from 96 patients with prostatic cancer entered into various National Prostatic Cancer Project protocols. Elevated placenta-like isoenzyme levels were found in 19 patients (20 per cent). Increased isoenzyme activity was seen in some patients with early clinical stages of the disease (B1 and B2), as well as in those with advanced disease. As in other reports results were not consistent in any individual patient. No correlations could be made between elevated isoenzyme activity and either stage of the disease or response to therapy. The placenta-like isoenzyme of alkaline phosphatase appears to be a nonspecific oncodevelopmental marker that is not helpful alone as a diagnostic indicator but that may be promising as part of a profile of markers for a patient with prostatic cancer.

Alkaline Phosphatase↗
PubMed1982

Hybridoma antibody to breast cancer immune complexes.

Hybridoma clones were established by fusing spleen cells from mice immunized with purified breast cancer-related immune complexes to drug-resistant nonproducing myelomas. Hybridoma cultures were evaluated for antibody production using immunofluorescence, radioimmunoassay and immunoperoxidase techniques. One antibody demonstrated strong reactivity against breast tumor cells (BT-20) in culture and also was found to bind ductal epithelial cells within sections of human mammary tissue. Antigen was detected within the soluble fraction of breast tumors with molecular weight greater than 500 K. The possible relationship between antigen detected in breast tumor cells and in immune-complexed form is discussed.

Antibodies, Monoclonal↗
PubMed1982

Immunochemical characterization of prostatic acid phosphatase with monoclonal antibodies.

Hybridoma-derived monoclonal antibodies to human PAP have been produced by fusion of mouse myeloma cells [P3 x 63 Ag 8.653] with spleen cells from mice immunized with purified PAP. One hundred fifty-six out of 252 clones were found to produce antibodies against PAP. These monoclonal antibodies were classified into four different subclasses as IgM [3 clones], IgG2a [2 clones], IgG3 [1 clone], and IgG1 (150 clones] with k-chains. Four monoclonal antibodies, IgG1, IgG2 a, IgG3, and IgM, were selected from the 156 hybridoma clones for immunologic characterization. Results from a binding assay suggested that monoclonal anti-PAP antibodies IgG1 and IgM recognized two distinct antigenic determinants of the PAP molecule, while the hybridoma IgG2a and IgG3 antibodies recognized another antigenic determinant. The specificity of these four hybridoma anti-PAP antibodies has been evaluated by the immunohistochemical method and competitive-binding assay. Monoclonal antibodies IgG2a and IgG3 as well as polyclonal xenoantibodies were found to react with PAP as well as with nonprostatic acid phosphatases; and antibodies IgG1 and IgM reacted more specifically with PAP. These results indicated that monoclonal anti-PAP antibodies IgG1 and IgM possessed a higher specificity for human PAP in comparison with monoclonal antibodies IgG2a, IgG3, and xenoantibodies. The monoclonal anti-PAP IgG1 and IgM antibodies may be useful in delineating antigenic structure of the PAP molecule, as well as in the refinement of serologic determination and immunocytochemical study of PAP in human prostate cancer.

Acid Phosphatase↗
PubMed1982

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Acid Phosphatase↗
PubMed1982

A simplified purification procedure for human prostate antigen.

Methods for purifying the human prostate specific antigen are described. The antigen was isolated from human prostate and seminal plasma. Purified antigen (ca. 1 mg/ml) from seminal plasma was immunologically identical and biochemically similar to that of prostatic tissue.

Antigens↗
PubMed1982

Multiple marker evaluation in human prostate cancer with the use of tissue-specific antigens.

Serum prostate-specific antigen and prostatic acid phosphatase were simultaneously evaluated in 22 healthy males, 29 patients with benign prostatic hypertrophy, and 192 patients with prostate cancers at various stages as well as in 30 patients with cancers other than prostate cancer. Both markers were quantitated by specific sandwich-type, enzyme-linked, immunosorbent assays with the use of specific antiserum reagents. Serum assays revealed a discordance between these two markers; thus expressions of these two biochemically and immunologically distinct prostate-specific proteins may reflect different aspects in the biology of prostate cancer. A combination test with the use of 7.5 ng of prostate antigen and 15.5 ng of prostatic acid phosphatase/ml of serum, respectively, as cutoff values resulted in a positive detection rate of 58% for prostate cancers of stages A (7/12) and B (21/36) each, 68% for prostate cancer of stage C (19/28), 92% for prostate cancer of stage D (106/116), and only 10% for benign prostatic hypertrophy (3/29). None of 52 other cancers or healthy controls was registered as positive. This study demonstrates that a multiple marker test of tissue-specific antigens can be of an additive value in the immunodiagnosis of cancer and may be a logical and effective approach at this time, in light of the unavailability of human tumor-specific markers.

Acid Phosphatase↗
PubMed1982

Monoclonal antibodies to a human prostate antigen.

Three monoclonal antibodies reactive with a purified extractable Mr 34,000 prostate antigen (PA) have been prepared by fusing splenocytes of BALB/c mice preimmunized with purified PA with the NS1 mouse myeloma cell line. The three antibodies were all of the IgG-1 subclass. The antibodies defined two noncross-blocking unique determinants on PA; each present as one site per molecule. IF3 defined one antigenic site and 2G7 and 1C5 defined another antigenic determinant. All of the antibodies reacted with PA in a solid-phase radioimmunoassay and immunoprecipitated 125I-labeled PA. Absorption and sandwich radioimmunoassays showed PA in prostate tissues but not in tonsil, liver, or kidney. Immunoperoxidase staining of formalin-fixed paraffin-embedded sections of benign prostatic hyperplasia and prostatic carcinoma revealed strong prostate epithelial reactivity. None of the antibodies showed reactivity with prostate membrane preparations. A sandwich radioimmunoassay used 2G7 as a plate coat. 125I-labeled 1F3 was used to detect 5 ng PA per ml in sera of patients with prostate cancer. These results confirm previous observations regarding the specificity of PA and shed new evidence for its intracellular localization.

Antibodies, Monoclonal↗
PubMed1981

Evaluation of a human pancreas-specific antigen by enzyme-linked immunosorbent assay.

A sensitive sandwich-type enzyme immunosorbent assay has been developed for quantitation of a new human pancreas-specific antigen (PaA). With this method, PaA at a concentration as low as 0.8 ng/ml can be detected. The assay was reproducible as shown by the coefficients of variation for within (4.8%) and between (6.1%) assays. Serum PaA levels from 51 healthy persons ranged from less than 4 to 34 ng/ml. Using 21.5 ng/ml (the upper 97.5 percentile of normal controls) as an upper limit, 42 of 60 pancreatic cancer (70%), 3 of 14 pancreatitis (21%) and 2 of 6 cholelithiasis (33%) had an elevated PaA. Very few patients with other cancers were shown to have an elevated PaA: 3/40 (8%) of lung cancer, 2/43 (5%) of colorectal cancer, 3/40 (8%) of prostate cancer and 1/39 (3%) of breast cancer. The sensitivity and specificity of the serum PaA test for the detection of pancreatic cancer were calculated to be 70% and 95%, respectively. These results indicate that PaA may be useful as an adjunctive tool in immunodiagnosis of pancreatic cancer.

Antigens, Neoplasm↗
PubMed1981

Prostatic-specific antigen: an immunohistologic marker for prostatic neoplasms.

Antiserum to a human prostate-specific antigen was raised in a rabbit and utilized by immunoperoxidase staining to evaluate its potential value as a diagnostic histologic marker for tumors of prostatic origin. All primary and metastatic prostatic malignancies reacted positively, whereas nonprostatic neoplasms did not stain with this procedure. This is the first immunohistochemical marker for prostate gland epithelium which does not represent prostatic acid phosphatase.

Adenocarcinoma↗
PubMed1981

Purification and characterization of a human pancreas-specific antigen.

A pancreas-specific antigen was identified by immunologic techniques and purified from saline extract of human pancreas. The purified pancreas-specific antigen was shown to be homogeneous by polyacrylamide gel electrophoresis under both denaturing and non-denaturing conditions. It had a molecular weight of 44000 as estimated by gel filtration or sodium dodecyl sulfate-gel electrophoresis, and a sedimentation coefficient of 3.4 S as analyzed by sucrose gradient centrifugation. Pancreas-specific antigen possessed an isoelectric point of 4.9 and migrated to alpha-beta region upon immunoelectrophoresis. By colorimetric assay procedures, pancreas-specific antigen exhibited no enzyme activity, such as amylase, protease, esterase, lipase, acid phosphatase, alkaline phosphatase peroxidase, deoxyribonuclease or ribonuclease. Immunoreactivity of pancreas-specific antigen was sensitive to proteolytic enzymes, perchloric acid and high temperature (70 degrees C, 10 min); but insensitive to neuraminidase or beta-glucosidase. Immunohistochemical staining revealed that pancreas-specific antigen was located in acinar cells of human pancreas. In addition, a higher concentration of pancreas-specific antigen was detected in pancreatic juice than in the saline extract of pancreas. This newly identified pancreas-specific antigen, therefore, may be a useful marker protein in physiological studies of pancreas and pancreatic secretion.

Animals↗
PubMed1981

Isolation, characterization and clinical evaluation of a pancreas cancer-associated antigen.

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.

Animals↗
PubMed1981

A statistical evaluation of baseline and follow-up carcinoembryonic antigen in patients with resectable colorectal carcinoma.

A long-term CEA follow-up was evaluated statistically for a series of 74 patients with primary colorectal carcinoma who underwent resections for cure. Thirty-three recurrences and 29 deaths were reported among this population after a median follow-up interval of 55 months. Preoperative CEA levels correlated with the Dukes' classification. However, the preoperative level adds significant information to Dukes' classification in the prediction of recurrence. Postoperative CEA assays taken later in the clinical evaluation process carry the most prognostic information for subsequent recurrence. Using matched-pairs techniques, the authors noted that CEA often rose in anticipation of recurrence, sometimes as early as one year before recurrence. The following four follow-up CEA events were evaluated: 1) three consecutive rising CEA's 2) CEA rises 5.0 ng/ml; 3) CEA exceeds 5.0 ng/ml; 4) CEA exceeds 5.0 ng/ml two consecutive times. The follow-up CEA events examined were characterized by false positive rates ranging from 17% to 66% and true positive rates ranging from 43% to 56% in the prediction of recurrence. From follow-up CEA evaluations, further clinical investigation appeared most warranted when CEA exceeds 5.0 ng/ml at two consecutive follow-up evaluations, but the chances of finding any subsequent recurrent disease was near 50%. Among patients experiencing recurrences, although forewarned by CEA elevations, there was no subsequent time when patients were most likely to have recurrence of disease.

Carcinoembryonic Antigen↗
PubMed1981

Carcinoplacental isoenzyme (Regan) in carcinoma of the prostate. National Prostatic Cancer Project.

Serum samples were examined for the placental-like "Regan" isoenzyme of alkaline phosphatase in two groups of patients with advanced cancer of the prostate from clinical trials of the National Prostatic Cancer Project. In the first group, 98 samples from 76 patients over three consecutive months revealed elevated isoenzyme activity in 14 (18%) of the patients, a frequency similar to those reported for some other tumor types. Four of these patients whose serum demonstrated the "Regan" isoenzyme had samples taken more than once, and their sera had negative readings when taken a month or more before or after the sample that was positive for the isoenzyme. Comparisons of general disease and patient characteristics for patients whose sera were positive or negative for Regan isoenzyme revealed no demonstrable relationships. The second group consists of 72 samples received from 52 study patients with metastatic lesions under treatment from August 1, 1979 to November 16, 1979. Fifteen patients had sufficient serial values. In this study to date, the relationship with clinical response to treatment is inconclusive, although elevated levels of the isoenzyme appear to occur in patients with metastatic disease with bony lesions that are clinically in progression, as well as in those apparently responding to chemotherapy.

Aged↗