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N Zamcheck

Publications and source records attributed to N Zamcheck.

At least 55 records · Page 3Linked to original sources

An evaluation of two antigen nonspecific assays for circulating immune complexes using a model system.

Two methods of detecting circulating immune complexes (CIC) in serum, the Protein A-glass fiber filter assay (PA-GFF) and the polyethylene glycol (PEG) insolubilization assay, were compared using a model system of BSA/anti-BSA. Supernatants of the quantitative precipitin curve from extreme antigen excess through antibody excess were tested by both methods. The PEG assay detected soluble CIC in all areas where expected by comparison with the Farr Test; the filter assay did not, although it did detect aggregated globulins quantitatively. The PEG assay detected high levels of CIC in serum of rheumatoid arthritis patients and low levels in normal human serum. Postprandial samples and plasma with heparin or EDTA caused unpredictable increases in results in the PEG assay so that for best results the PEG assay should be run on serum from fasting individuals. PEG insolubilized complexes were analyzed and found to contain expected serum components. A slight modification of the original method was made and tested using two other model complex systems and known CIC-containing sera. The PEG turbidity assay it fast, easy, reproducible, and suitable for quantitating and isolating immune complexes in serum.

Animals↗

Circulating immune complex levels in patients with gestational trophoblastic neoplasia.

The clinical course, human chorionic gonadotropin (HCG) levels, and serial circulating immune complex (CIC) levels in 21 patients with gestational trophoblastic neoplasia (GTN) were correlated for the evaluation of the relationship between CIC levels and trophoblastic tumor burden. CIC levels were normal in 18 of 21 patients at the time of presentation, and 2 of 3 patients who presented with elevated CIC levels had significant comorbid disease (toxemia and hepatitis). Nine patients were followed into gonadotropin remission, and all 9 developed an increase in CIC levels at the time of remission. It was concluded that CIC, at least as measured by two antigen-nonspecific techniques, is generally not elevated at initial presentation in the patient with GTN; this lack of an elevation is probably due to marked tumor antigen excess. Thus the in vivo importance of CIC as a "blocker" of host antitumor response at this stage is doubtful. After effective treatment as HCG levels return to normal, the demonstrated elevation in serial levels of CIC may reflect a return of adequate host immune response at a time of minimal tumor burden.

Adolescent↗

Carcinoembryonic antigen in nonhuman primates.

Blood levels of carcinoembryonic antigen (CEA) have been measured in several nonhuman primate species. Only gorillas and chimpanzees were found to have significant elevations of CEA-like activity in their blood compared to the normal values of less than 2.5 ng/ml in humans. The average CEA level in 134 chimpanzees was 25.2 ng/ml (range, 4.2--95 ng/ml) and in 13 gorillas it was 32 ng/ml (range, 12.4--61.9 ng/ml). These levels were not related to sex. Blood levels repeatedly taken over a 1 1/2-year period remained relatively stable in both species. Analysis of parallelism of immunologic reactivity showed chimpanzee CEA to be similar to but not identical with human CEA. The molecular size of chimpanzee CEA was also similar to that of human CEA.

Animals↗

Retention of carcinoembryonic antigen on Sephadex G-50 and acrylamide gel buffer-exchange columns.

We compared the degree of retention of carcinoembryonic antigen on two types of buffer-exchange columns, Sephadex G-50 and acrylamide gel. Both types retained trace amounts of the antigen applied in the form of a perchloric acid extract, as measured by its release into plasma samples subsequently processed through the same columns, Cross contamination, resulting in values falsely high by greater than 1 microgram/L, was observed when columns were re-used after processing plasma samples with carcinoembryonic antigen concentrations greater than 700 micrograms/L.

Blood Chemical Analysis↗

Carcinoembryonic antigen. A useful monitor of therapy of small cell lung cancer.

In 85 patients with small cell cancer of the lung, the degree of carcinoembryonic antigen (CEA) elevation correlated with the extent of disease. Normal CEA levels (less than 2.5 ng/mL) occurred in 55% of patients with limited disease compared with 12% of patients with extensive disease. All patients with CEA levels greater than 50 ng/mL had liver involvement. Serial CEA levels were useful in monitoring response to chemotherapy and in predicting relapse. All patients with CEA values greater than 5.0 ng/mL before start of treatment had a fall in CEA level with response to treatment and a rise in CEA level when resistance to chemotherapy developed. In patients with CEA levels of less than 5.0 ng/mL at the start of treatment, rising values reflected the onset of recurrent disease in 10 or 21 patients who had relapses. The CEA levels used in conjunction with standard roentgenograms and organ scanning studies can aid in the initial staging of small cell cancer of the lung, and in monitoring treatment.

Aged↗

Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group.

One-hundred-ninety-four eligible and evaluable patients with histologically confirmed locally unresectable adenocarcinoma of the pancreas were randomly assigned to therapy with high-dose (6000 rads) radiation therapy alone, to moderate-dose (4000 rads) radiation + 5-fluorouracil (5-FU), and to high-dose radiation plus 5-FU. Median survival with radiation alone was only 51/2 months from date of diagnosis. Both 5-FU-containing treatment regimens produced a highly significant survival improvement when compared with radiation alone. Forty percent of patients treated with the combined regimens were still living at one year compared with 10% of patients treated with radiation only. Survival differences between 4000 rads plus 5-FU and 6000 rads plus 5-FU were not significant with an overall median survival of ten months. Significant prognostic variables, in addition to treatment, were pretreatment performance status and pretreatment CEA level.

Adenocarcinoma↗

Correlation of Plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer.

A review of patients operated on for colorectal cancer disclosed poorly differentiated histologies in those whose preoperative and postoperative carcinoembryonic antigen (CEA) levels were no elevated, even in the presence of metastatic disease. CEA was therefore, of little prognostic value or predictive of disease recurrence in these patients. The amount of CEA in tumor tissue of 17 patients with poorly differentiated colorectal cancer was estimated with the immunoperoxidase staining technique and was correlated with histology and plasma CEA levels obtained during various stages of disease. Five tumors did not stain negatively for CEA and all had predominantly poorly differentiated histologies. In all of these patients metastatic disease developed but not elevated plasma CEA levels. In contrast 12 tumors stained positively for CEA and were found to contain either differentiated areas or signet ring cells. Serial plasma CEA levels correctly monitored the postoperative course of all 12 patients. Six of these had a relapse and all were detected by serial increases in plasma CEA. The remaining six were disease free greater than 48 months after resection and had normal plasma CEA levels. Among poorly differentiated tumors, those that contain glandforming areas or signet ring cells can be assumed to produce CEA and plasma CEA levels can be used effectively for monitoring. On the other hand, undifferentiated tumors which do not stain for CEA identify those patients whose plasma CEA levels do not provide a useful monitor.

Adenocarcinoma↗

Application of polyethylene glycol turbidity assay to detection of circulating immune complexes in cancer patients.

A rapid, reproducible immune complex screening assay was used to quantitate levels of circulating immune complexes in the sera of normal subjects, patients with documented increases in immune complexes from rheumatoid arthritis, patients with clinically or microbiologically documented infections, and patients with cancer. Although wide variations in individual values within the groups were noted and the concurrent elevation of polyethylene glycol-circulating immune complex levels by infection was documented as expected, significant differences were found in the values in patients with cancer compared with those in normal subjects. The overall clinical application of polyethylene glycol-circulating immune complex screening is discussed and current application of screening of serial sera samples from individual patients for correlation with measurable tumor volume is proposed.

Antibodies, Neoplasm↗

Immunocytochemical localization of carcinoembryonic antigen in benign and malignant colorectal tissues. Assessment of diagnostic value.

Immunoperoxidase and immunofluorescence staining for carcinoembryonic antigen (CEA) was performed on paraffin and frozen sections, respectively, of colonic carcinomas (70), liver and lymph node metastases (20), mesenteric nodes (150), mucosa adjacent to carcinoma (40), colonic resection margins (20), normal colon (ten), and colorectal polyps (64) in order to assess its potential diagnostic value. On the basis of this study of the immunocytochemical localization of CEA in colorectal tissues, conclusions were as follows. (1) Localization of CEA to glycocalyx of surface epithelial cells is a normal finding in the colon and is similar in normal colon and mucosa distant and adjacent to infiltrating carcinoma. (2) Although strongly positive cell surface and intraluminal staining frequently correlates with the presence of carcinoma in neoplastic polyps, it is not by itself a reliable diagnostic criterion. (3) Failure to demonstrate CEA in a gland-forming carcinoma makes a diagnosis of colorectal carcinoma unlikely. (4) Poorly differentiated colorectal carcinoma usually contains much less demonstrable surface CEA, but may occasionally stain cytoplasm strongly. (5) Although lymph node micrometastases from colorectal carcinoma are readily demonstrated by immunoperoxidase staining for CEA, screening of hematoxylin and eosin-stained sections by a competent pathologist appears to be adequate for their detection.

Carcinoembryonic Antigen↗

Carcinoembryonic antigen gradients between plasma and malignant ascites: use in detecting peritoneal and liver metastases.

In the study of 19 patients with malignant ascites and elevated plasma carcinoembryonic antigen (CEA) (greater than 2.5 ng/ml) and/or ascites CEA (greater than 10 ng/ml), two patients emerged: 1) The 10 patients with higher ascitic fluid than plasma CEA levels (medians: 230 and 10.6 ng/ml, respectively) had exudates and intraperitoneal cancer but usually had no hepatic metastases. 2) The 9 patients with lower ascitic fluid than plasma CEA levels (medians: 29 and 140 ng/ml, respectively) had transudates and negative cytology examinations but did have demonstrable liver metastases. Determination of ascitic fluid and plasma CEA gradients in patients with malignant ascites may help localize, with potentially therapeutic importance, the site of metastases.

Ascites↗

Monoclonal antibodies to carcinoembryonic antigen produced by somatic cell fusion.

Hybridoma cell lines secreting monoclonal antibodies to carcinoembryonic antigen (CEA) were generated by fusing mouse immune lymphocytes with the mouse myeloma variant cell line, NS-1. Antibody secreted by one cloned hybrid cell line could bind only a select portion of the CEA bound by the commercially available goat anti-CEA antiserum used in clinical assays. Radiolabeled CEA could be purified on a monoclonal antibody affinity column. Incorporation of this purified radiolabeled CEA in a double-antibody solid-phase assay with goat anti-CEA antiserum led to an approximately 2.5-fold increase in sensitivity of the assay. Genetically stable hybrid clones may be sources of virtually unlimited quantities of such antibodies which may have potential utility in improving the cancer specificity of clinical assays.

Animals↗

The use and limitations of serial plasma carcinoembryonic antigen (CEA) levels as a monitor of changing metastatic liver tumor volume in patients receiving chemotherapy.

Nine patients with liver-predominant or liver-only metastatic adenocarcinoma, who received hepatic intra-arterial and peripheral intravenous chemotherapy, were evaluated to determine if changes in plasma CEA accurately indicated changes in liver tumor volume as estimated from serial liver scan defect sizes, and if the two were quantitatively related. When selected periods of tumor remission or progression were studied during chemotherapy, the index of change of serial CEA values correlated positively (r = 0.764, P = 0.01) with the index of change of liver tumor volume in all 9 cases. Changes in absolute CEA values, however, aid not correlate significantly with changes in absolute liver tumor volumes when assessed either during these selected periods or throughout individual patient courses. Biologic and methodologic factors that influence the quantitative relation between liver tumor volume and plasma CEA are discussed.

Adenocarcinoma↗

Cholestasis and hepatic metastases: a factor contributing to extreme elevations of carcinoembryonic antigen.

Records of 19 autopsied patients with metastatic carcinoma were studied to elucidate the contribution to the elevation of antemortem plasma carcinoembryonic antigen (CEA) levels (range, 5.9--136,000 ng/ml) of 1) liver pathology and dysfunction, 2) tumor morphology and CEA content, and 3) tumor spread and location. Liver function tests and plasma CEA recorded within 8 weeks of death, autopsy records of tumor spread, liver weight (as an index of liver tumor mass), and histologic sections were reviewed. Tissue CEA was demonstrated in 15 patients by an immunoperoxidase method. Cholestasis was seen in histologic sections of tissue from 8 of 10 patients, and elevated bilirubin was seen in 7 of 10 patients with hepatic metastases and CEA levels greater than 1,000 ng/ml In contrast, histologically observed cholestasis and elevated bilirubin were seen in only 1 of 8 patients with CEA less than 500 ng/ml. A significant correlation was found between the plasma CEA level and histologically observed cholestasis (P less than 0.01). Serum bilirubin also correlated significantly (P less than 0.01), but alkaline phosphatase did not. Liver weight (tumor mass) showed a positive correlation with cholestasis (P less than 0.01) but not with circulating CEA. Markedly elevated plasma CEA levels (greater than 1,000 ng/ml) seen preterminally may partially reflect impaired excretion of CEA by the hepatobiliary system rather than, or in addition to, preterminal increase in CEA-producing tumor.

Bilirubin↗

The use of preoperative plasma CEA levels for the Stratification of patients after curative resection of colorectal cancers.

One hundred forty-five patients with colorectal cancer were analyzed in order to correlate the preoperative plasma carcinoembryonic antigen (CEA) levels with the sites and times of disease recurrence. The median follow-up periods of these patients was 50 months (range 36-72 months). Twenty-one patients were found to have metastases at the time of their operation. None of the seven patients whose primary tumors were classified as Dukes/Kirklin A have had tumor recurrence. Seventeen per cent of the patients with Dukes/Kirklin B tumors have had tumor recurrences, and 63% of the patients with Dukes/Kirklin C colorectal primary tumors have had tumor recurrence. No correlation was found between preoperative CEA values and subsequent risk of tumor recurrence or times to recurrence among the patients with Dukes/Kirklin B colorectal primary cancers. In Dukes/Kirklin C patients, however, elevated preoperative CEA values predicted a higher risk of tumor recurrence. Ninety per cent of the patients (19/21) with preoperative CEA levels greater than 5.0 ng/ml have had relapses, with a median time of 17 months before disease recurrence. Only 39% (9/23) of the patients with Dukes/Kirklin C lesions and CEA levels less than 5 ng/ml have had relapses and there is insufficient follow-up data as yet to determine the median survival time. If those patients whose Dukes/Kirklin C primary tumors were poorly differentiated on histologic examination are excluded, the contrast between patients having CEA levels greater than 5.0 ng/ml and those having CEA levels less than 5 ng/ml is even more marked. Sixteen of the 18 remaining patients whose CEA levels were greater than 5.0 ng/ml prior to curative resection have had relapses as compared with only three of 15 patients whose preoperative CEA values were less than 5. We conclude, therefore, that CEA is an important factor in stratifying patients after curative resection of their Dukes/Kirklin C colorectal tumors.

Carcinoembryonic Antigen↗