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Biomedical subjects

N Zamcheck

Publications and source records attributed to N Zamcheck.

At least 19 recordsLinked to original sources
PubMed1990

Differential reactivities of carcinoembryonic antigen (CEA) and CEA-related monoclonal and polyclonal antibodies in common epithelial malignancies.

To evaluate the role of carcinoembryonic antigen (CEA) in solving problems of tumor histogenesis in surgical pathology, monoclonal antibodies to four distinct epitopes of CEA (E-Z-EM) were applied to paraffin sections of 303 epithelial neoplasms from multiple sites. Two epitopes were CEA specific (D14 and B7.1), one was shared with nonspecific cross-reacting antigen (NCA) (B7.8), and the fourth (B18) was common to CEA, NCA, and biliary glycoprotein antigen (BGP). A sample of the tumors (n = 110) was also stained with a polyclonal anti-CEA (DAKO). Gastrointestinal adenocarcinomas, including esophageal and gastric (n = 19), small intestinal (n = 8), colorectal (n = 56), biliary tract (n = 8), and pancreatic adenocarcinomas (n = 14), were consistently positive with all five antibodies. Other predominantly gland-forming carcinomas tested, comprising lung (n = 22), ovary (n = 18), and endometrium (n = 12), were either invariably negative with all five antibodies (endometrial adenocarcinoma, non-mucinous ovarian adenocarcinoma) or demonstrated selective and variable positivity (lung: D14, 50%; ovarian mucinous: D14, 50%). Among large polygonal cell carcinomas (hepatocellular carcinoma, renal cell carcinoma, melanoma, and adrenal carcinoma), only hepatomas stained positively, showing a distinctive canalicular staining pattern with the B18 (BGP epitope) (55%) and polyclonal antibody (50%). In the small polygonal cell carcinoma category, true CEA positivity was rare in breast (D14, 10% and B7.1, 14%) and never seen in prostatic carcinomas and carcinoid tumors. A subset of these breast (8 of 42), prostate (4 of 22), and carcinoids (4 of 7) showed exclusive positivity for the B18 antibody (NCA/BGP epitope). Ovarian serous papillary carcinomas (n = 14), papillary carcinomas of thyroid (n = 12), transitional cell carcinomas of the bladder (n = 11), and mesotheliomas (n = 3) were negative with all monoclonal antibodies. Metastatic carcinomas (n = 74) showed a similar pattern of reactivity to primary tumors. The authors conclude that CEA immunostaining may assist in identifying the histogenesis of epithelial tumors in several morphologic categories; that differential reactivities of the CEA monoclonal antibody panel exceed those of the polyclonal antibody; and that the discriminating power of the monoclonal panel is related to whether (1) CEA is or is not produced or (2) NCA or BGP is produced without concomitant CEA production. There is little evidence to support a concept of site-specific CEA species.

Antibodies, Monoclonal↗
PubMed1979

Isoelectric focusing in agarose.

We describe here the use of a new agarose for isoelectric focusing of body fluids and tissue proteins. Macromolecular proteins even when significantly greater in size than 1 X 10(6) mol.wt. were easily and rapidly focused.

Adenocarcinoma↗
PubMed1979

Direct tissue isoelectric focusing in agarose.

We are isoelectric focusing small amounts of tissues placed directly on electroendosmosis-free agarose gels instead of using the saline extracts of tissue homogenates. More numerous proteins are extracted during isoelectric focusing of the solid tissues than present in the same tissues.

Adenocarcinoma↗
PubMed1978

Randomized phase II clinical trial of adriamycin, methotrexate, and actinomycin-D in advanced measurable pancreatic carcinoma: a Gastrointestinal Tumor Study Group Report.

Sixty-six patients with advanced pancreatic carcinoma were randomized to receive single agent chemotherapy with either adriamycin, methotrexate, or actinomycin-D using conventional dose, route and schedule of administration. All patients had measurable lesions which were used to objective assessment of response. For adriamycin, 2 of 25 patients (8%) evidenced a partial response (2 of 15 (13%) previously untreated patients). One of 25 patients treated with methotrexate and one of 28 received actinomycin-D responded. The duration of responses ranged from 43-64 days for those patients with no chemotherapy prior to study entry. The median survival of patients who received adriamycin as initial treatment was 12 weeks compared to 8 weeks for methotrexate and 6 weeks for actinomycin-D therapy.

Adult↗
PubMed1978

Carcinoembryonic antigen (CEA) levels in benign gastrointestinal disease states.

Elevated circulating CEA levels occur in patients with benign gastrointestinal and hepatic disorders. These are usually less than 10 ng/ml. Of clinical importance is the influence of liver disease on the interpretation of CEA. At least 50% of patients with severe benign hepatic disease have elevated CEA levels, most often active alcoholic cirrhosis, and also chronic active and viral hepatitis, and cryptogenic and biliary cirrhosis. Patients with benign extrahepatic biliary obstruction may have increased plasma CEA, the highest in patients with co-existent cholangitis and especially liver abscess. The liver appears to be essential for the metabolism and/or excretion of CEA. Hence, liver work-up is needed to assess any patient with an elevated CEA. A damaged liver may further augment elevated CEA levels due to cancer. The increased circulating CEA observed in some patients with active ulcerative colitis tends to correlate with severity and extent of disease and usually returns to normal with remission. CEA levels also may be mildly elevated in patients with pancreatitis and in adults with colonic polyps. Smoking may contribute to the increased CEA levels seen in patients with alcoholic liver disease and pancreatitis. Therefore, in interpreting mildy elevated circulating CEA levels in patients with GI tract diseases, one must consider benign as well as malignant etiologies.

Animals↗
PubMed1978

Carcinoembryonic antigen (CEA) as a monitor of chemotherapy in disseminated colorectal cancer.

A rising CEA level is accepted as a sensitive indicator of recurrent colorectal carcinoma. In order to assess its efficacy in monitoring responses to chemotherapy in disseminated disease, 47 patients with documented metastatic colorectal cancer were studied. All had pretreatment CEA determinations and 40/47 (85%) patients had CEA levels greater than 4.0 ng/ml. Patients with hepatic metastases had the highest CEA values and none were found to have levels less than 4.0 ng/ml. Thirty patients received chemotherapy and had serial CEA determinations. 4/30 (13.3%) demonstrated probable tumor regression, 7/30 (23.3%) had stable disease, while 19/30 (63.3%) showed disease progression. CEA titers declined in all four responders, but in only one instance did the level fall to below 4.0 ng/ml and provide evidence of a tumor response not appreciated clinically. The only cytotoxic drugs effecting tumor regressions were 5-FU and 5-FUDR. CEA levels usually rose as disease progressed, but once elevated, absolute values did not correlate directly with tumor burden. The further usefulness of CEA assays in monitoring disseminated colorectal cancer awaits the development of improved chemotherapeutic agents.

Adult↗
PubMed1978

The disparity of indirect and direct zirconyl-gel assays for carcinoembryonic antigen.

Experience with the zirconyl phosphate gel (Z-gel) radioimmunoassays for plasma CEA levels below 20 ng/ml (the indirect method) and for levels greater than 20 ng/ml (the direct method) has shown that a disparity of values exists, caused by shifting from one assay to the other. This disparity is at least partially due to PCA-labile proteins reacting in the direct assay. It may be constant for individual patients but varies among patients. The magnitude of this disparity is independent of the CEA level (above 15 ng/ml).

Carcinoembryonic Antigen↗
PubMed1978

Present status of the zinc glycinate marker (ZGM).

ZGM was purified from both primary and metastatic colonic carcinomas demonstrably positive for ZGM by immunofluorescence microscopy. ZGM purification included preparative Pevikon electrophoresis, Sepharose 4B molecular exclusion chromatography and Con A-Sepharose affinity chromatography. ZGM had an alpha2 electrophoretic mobility, an estimated molecular weight by Sepharose 4B equal to or greater than 2 x 10(6), and did not bind to Con A-Sepharose, although having determinants with CEA-like activity. Its immunologic activity was resistant to trypsin or phospholipase A but not to neuraminidase. Antisera prepared to ZGM and absorbed with saliva, when tested by double immunodiffusion, formed a single precipitation line with saline extracts of colon tumors and did not cross-react with CEA, AFP, normal tissue extracts, ferritin, NCA, NCA-2, CSAp, blood groups A, B, H, Lewis antigen, or buffy coat, alpha-2 macroglobulin, saliva or ovarian cyst fluid. Immunofluorescence microscopy confirmed the presence of ZGM in 40 out of 45 adenocarcinomas of the GI tract staining primarily in tumors, the apical cytoplasm, and in grossly nonmalignant tissues, the deep crypts of the villi, while all of 22 non-GI tumors in the study were ZGM negative.

Antigens, Neoplasm↗
PubMed1978

Serial carcinoembryonic antigen (CEA) blood levels in patients with ulcerative colitis.

Fifty-seven patients with ulcerative colitis were folloued 1-49 months (mean, 18 months) with serial CEA determinations during periods of remission, mild relapses, and severe relapses. Elevated CEA titers correlated with activity and possibly extent of disease: 12% of patients with proctitis, 47% of patients with left-sided colitis, and 60% of patients with transverse or universal colitis had elevated CEA titers during a flare. Moreover, 24% of patients with mild flares and 86% of patients with severe flares had elevated CEA titers. Ninety-two percent of patients with extensive disease and severe flares had elevated CEA titers. Elevated CEA titers were correlated with histologic findings in three patients. Inflammation of mucosa was demonstrated by colonoscopy and confirmed by biopsy in one patient with persistently elevated CEA titers during clinical remission. In two other patients with active disease whose CEA titers fell prior to colectomy, marked denudation of colonic mucosa was noted. In this study, a transiently elevated CEA titer indicated either clinically active ulcerative colitis or active inflammation of colonic mucosa.

Carcinoembryonic Antigen↗
PubMed1978

Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. I. Preparation of antisera against the zinc glycinate marker.

Antisera against the zinc glycinate marker (ZGM) were produced in New Zealand White rabbits with induced tolerance to normal tissue components and CEA, and in mature, previously uninoculated rabbits for use in immunofluorescent histologic localization of ZGM in colon cancers and other tissues. Analysis of the antisera by immunodiffusion and counterimmunoelectrophoretic techniques showed them to be specific for ZGM when tested with ZGM, carcinoembryonic antigen, normal tissue extracts, or cell elements of normal blood.

Animals↗
PubMed1978

Tissue localization of zinc glycinate marker and carcinoembryonic antigen by immunofluorescence. II. Immunofluorescence microscopy.

Preliminary indirect immunofluorescence studies on the zinc glycinate marker (ZGM) were compared with carcinoembryonic antigen (CEA) immunofluorescence, ZGM, detected in 26 of 29 human colon adenocarcinomas, was associated with the epithelial component of the malignant glands. Fluorescence was generally less strong and more granular for ZGM than for CEA and was found in intraglandular spaces, luminal border areas, and cytoplasm. ZGM concentration and tissue localization appeared to be related to tumor differentiation. ZGM was also detected in benign colon mucosae (adjacent to and distant from the carcinomas) from patients with colon carcinoma, but differed from CEA in that it was present in the deep crypt portion only. Gastric, pancreatic, esophageal, and anal adenocarcinomas, as well as benign gastric pyloric and small bowel mucosae had detectable ZGM. CEA, but not ZGM, was observed in 20 nongastrointestinal carcinomas to date. Studies are under way to determine whether ZGM is a marker associated with colon and gastrointestinal adenocarcinoma specifically or undifferentiated crypt cells of the colon and digestive tract in general.

Adenocarcinoma↗
PubMed1978

Carcinoembryonic antigen levels in benign and malignant pleural effusions.

One hundred ninety-one unselected fluid specimens submitted routinely for cytologic examination were assayed to determine whether the measurement of carcinoembryonic antigen (CEA) levels in pleural effusions is useful in detecting malignancy. The mean +/- SD CEA level of 103 benign effusions was 4.1 +/- 2.9 ng/ml. Only one benign effusion had a level greater than 12 ng/ml (18 ng/ml). Benign inflammatory effusions (pneumonia, empyema) had a higher mean CEA activity (6.2 +/- 3.4) than effusions caused by congestive heart failure (2.9 +/- 1.5) (p less than 0.001). Twenty-four (34%) of 70 malignant effusions had a CEA level greater than 12 ng/ml, and 28 (40%) were "positive" by cytologic study. Thirty-eight (54%) were detected by one or both methods. Ten malignant effusions were positive by CEA (greater than 12 ng/ml) alone. These data suggest that the determination of CEA activity levels, when used in conjunction with other clinical findings, may be useful in detecting malignant pleural effusions.

Carcinoembryonic Antigen↗
PubMed1978

Carcinoembryonic antigen assay of ascites and detection of malignancy.

Levels of carcinoembryonic antigen (CEA) activity were measured in 105 unselected samples of ascitic fluid submitted for routine cytologic analysis to ascertain whether this assay was useful in the detection of malignancy. The highest CEA level found in the 70 specimens of "benign" ascites was 10 ng/ml. Using values greater than 10 ng/ml as indicating a cancerous effusion, CEA assay successfully detected 14 of the 29 malignant ascites studied. Cytology, on the other hand, detected only 12 of these fluids. Combining the two methods increased the yield to 20. The CEA assay alone thus detected more than one fourth of these malignant fluids. The assay was particularly useful in detecting malignant transudates, nearly half of which had elevated CEA levels despite negative cytologic findings. The CEA assay of ascites thus showed promise as an adjunct to cytology in the detection of malignant ascites when used as part of a complete clinical and laboratory assessment.

Ascitic Fluid↗
PubMed1978

Sequential carcinoembryonic antigen levels in the therapy of metastatic breast cancer: a predictor and monitor of response and relapse.

Serial measurements of plasma carcinoembryonic antigen (CEA) levels were analyzed in 42 patients with advanced breast cancer undergoing systemic chemotherapy. Pretreatment CEA levels exceeded 5 ng/ml in 22 patients, and 19 of 22 serial assays uniformly heralded tumor regression as well as subsequent tumor relapse. A significant quantitative alteration in CEA levels was established as a minimum change of 20% within 8 weeks of therapy. In 13 of 15 patients responding to chemotherapy and in all patients with CEA levels higher than 35 ng/ml, this criterion was not abrogated, and there were no discordant observations. Rising CEA levels were correlated with subsequent progression of disease in all patients with elevated baseline levels at a minimum of 8 weeks before the progression was clinically evident. In advanced breast cancer the effectiveness of therapy and the development of tumor resistance may be monitored by serial plasma CEA levels, and specific quantitative criteria should be applied.

Bone Neoplasms↗
PubMed1978

Circulating immune complexes in patients following clinically curative resection of colorectal cancer.

Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.

Adenocarcinoma↗
PubMed1978

Transient carcinoembryonic antigen (CEA) elevations following resection of colorectal cancer: a limitation in the use of serial CEA levels as an indicator for second-look surgery.

In a previous study, other investigators recommended second-look surgery for colorectal cancer primarily on the basis of plasma carcinoembryonic antigen (CEA) rises and prepared a nomogram for ready recognition of these "significant" increases. We found 25 patients whose CEA levels met the recommended criteria for significance; however, in 9 of these patients the rises were transient. Eight had no clinical evidence of recurrent cancer and they might have had negative second-look surgery had this been done because of CEA rises alone. The use of the CEA nomogram merely eliminated laboratory variation as a cause of the CEA rise. It did not, however, rule out biologic causes of CEA rises, other than that of cancer, especially benign liver disease. We were unable to differentiate benign from malignant rises on the basis of CEA changes alone. Preoperative CEA values helped to separate the two rises. Transient rises usually began earlier. Malignant CEA rises were more likely to be exponential. The rate of rise alone did not discriminate between the two rises. Thus, although serial CEA levels were helpful in making the decision for reexploration, they did not substitute for complete clinical assessment.

Carcinoembryonic Antigen↗