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H J Staab

Publications and source records attributed to H J Staab.

At least 37 records · Page 2Linked to original sources
PubMed1985

Monoclonal antibody-defined circulating human tumor-associated antigen with epitope shared by cytokeratins.

Sera of human colonic carcinoma xenografted rnu/nu rats were used to immunize rnu/+rats in order to obtain an immune response against circulating human tumor-associated components. After fusion of rat spleen cells with mouse myeloma cells monoclonal antibody MAB 108 could be established which reacted with two 40 and 45 kD cytokeratins as well as with vimentin, with a soluble 37 kD protein apparently derived from the 45 kD protein and with a 37 kD protein released by tumor cells. The MAB 108-specific epitope was also detected in tissue polypeptide antigen (TPA), a human tumor-associated antigen originally described by Björklund et al. (22).

Animals↗
PubMed1985

The clinical validity of circulating tumor-associated antigens CEA and CA 19-9 in primary diagnosis and follow-up of patients with gastrointestinal malignancies.

The clinical validity of monitoring the tumor markers carcinoembryonic antigen (CEA) and CA 19-9 were investigated in 602 patients with colorectal, gastric, and pancreatic carcinomas. Sensitivity and specificity of the tests were evaluated preoperatively as well as in the postoperative follow-up for early detection of disease progression and recurrence. At a 95% level of specificity as calculated from a group of 150 patients with benign diseases, the CEA test with monoclonal antibody had a preoperative sensitivity of 39% in colorectal cancer and 21% in gastric cancer. On the other hand, CA 19-9 had a sensitivity of 19% in colorectal cancer, 21% in gastric cancer, and 89% in pancreatic cancer. In the postoperative follow-up it was found that a combination of both tumor marker tests was most profitable in gastric carcinomas, yielding an increase of sensitivity from 59%-94%, showing a high degree of complementarity. The gain in sensitivity provided by the CA 19-9 test over the CEA-test in colorectal cancer was very low. The gain in sensitivity, however, provided by the CEA test over the CA 19-9 test in pancreatic carcinoma was also very low. On the basis of these results it has to be recommended that cases with pancreatic carcinoma are to be monitored most efficiently with the CA 19-9 test, whereas in cases with colorectal cancer the CEA test should be used primarily. However, in gastric cancer the combined use of CEA and CA 19-9 represents a highly valuable basis for monitoring the course of disease.

Antibodies, Monoclonal↗
PubMed1985

Prognostic value of preoperative serum CEA level compared to clinical staging: III. An approach to scoring of prognostic factors in colorectal cancer.

In a clinical study of observed postoperative survival of colorectal cancer patients, we investigated the application of a risk score based on tumor-related prognostic parameters. Six hundred seventy-four patients have been registered for primary surgery of colorectal cancer since 1974 who did not receive further postoperative treatments. The prognostic parameters included operability, tumor extension, and preoperative serum carcinoembryonic antigen (CEA) level. The scoring system was based on the average death-rate ratios of subgroups of patients and their age and sex-matched reference groups derived from the general life table of the population of the Federal Republic of Germany. The individual score sums of the patients exhibited score sum ranges which characterized groups of patients with entirely different observed survival. The prediction of individual survival after primary operation was only partly possible. In the plot of individual survivals vs individual score sums, a marginal risk zone was obtained which evidently represents the zone of maximum expected survival of patients who do not receive further postoperative treatment.

Aged↗
PubMed1985

Eighty-four potential second-look operations based on sequential carcinoembryonic antigen determinations and clinical investigations in patients with recurrent gastrointestinal cancer.

In our study of patients with resected primary gastrointestinal cancer, slope analysis of the post-operatively increasing carcinoembryonic antigen time courses signaled relapse in about 80 percent of the patients up to 12 months before positive clinical diagnosis. In 29 patients, clinical confirmation of the relapse could be obtained only after second-look surgery. Slope analysis generally differentiated localized from metastatic disease and therefore also predicted the site of relapse. A first evaluation of 84 patients with potential cases of second-look operations provided evidence for a significant increase in survival. Recently, the evaluation of individual carcinoembryonic antigen doubling times was used to derive an individual prognosis since doubling times strongly correlated with the survival of untreated patients. On this basis, it was clearly possible to show the benefit of second-look operation, since patients with resectable recurrences exhibited longer survival times compared with patients with similar carcinoembryonic antigen doubling times without treatment. Moreover, the introduction of monoclonal antibodies with increased specificity for malignant states, has facilitated the selection of patients for second-look operation because unspecific carcinoembryonic antigen elevations are less frequent and recurrent disease can be predicted more reliably due to the higher carcinoembryonic antigen increments associated with malignant growth.

Actuarial Analysis↗
PubMed1985

Differentiation of disease recurrence in various primary malignancies using CEA slope analysis.

CEA slope analysis was performed for patients with various primary malignancies who developed recurrent disease. In 340 cases CEA slopes could be calculated, and in 289 cases correlated with distinct diagnosis of recurrent disease. Local recurrence showed a slope range of 0.02-15.2 micrograms CEA increase/l serum/10 days (median = 0.28) and metastatic spread a slope range of 0.03-456 micrograms CEA increase/l serum/10 days (median = 0.98). Subgroups of patients with metastatic spread to the liver, bone, peritoneum and other sites had distinct CEA slope distributions independent of the primary tumors. Comparable slope ranges were found with two different commercially available kits, one a radioimmunoassay (antiserum) and the other enzyme-immunoassay (monoclonal antibody).

Carcinoembryonic Antigen↗
PubMed1985

Comparison of a CEA-EIA assay based on monoclonal antibody with a CEA-RIA assay with polyclonal antiserum.

A monoclonal CEA-EIA assay is evaluated with respect to clinically pertinent data. Comparison is done with the conventional CEA-RIA assay (Roche). Good interlaboratory reproducibility was found, and the stability was very good over the one year evaluation period. The EIA assay could be performed in samples of serum and plasma with compatible results. The correlation between the EIA and RIA values was different in different diagnostic groups, with high correlation in colo-rectal cancer, and low in non-malignant diseases, in which the EIA assay had a lower frequency of CEA positive values. In colo-rectal cancer the RIA assay shows a 20% specificity improvement compared with the EIA assay. This was also reflected in better predictability for true positive and true negative cancer diagnosis in this group of patients as well as increased ability to discriminate between malignant and non-malignant diseases. In other groups of patients, like lung cancer and uterine cervical cancer, such improvement was not seen. The discrimination between malignant and non-malignant diseases was comparable to that of the RIA assay. In follow-up series the EIA and RIA assays detected recurrences and responses to treatment in a quite similar way. In most cases of recurrences from colo-rectal cancer, however, the EIA values increased faster and were a better indicator for recurrent disease than the RIA values.

Antibodies, Monoclonal↗
PubMed1985

Optimizing tumor markers in breast cancer: monitoring, prognosis, and therapy control.

The clinical validity of tumor markers in breast cancer is reevaluated. Though ideal tumor markers are presently not available for breast cancer patients, optimizing markers can be achieved, applying markers in special situations and in selected fields of oncology. Tumor markers like carcinoembryonic antigen (CEA) and tissue polypeptide antigen are only of limited value in the primary diagnosis of breast cancer due to their low sensitivity and their poor specificity. Single postsurgical CEA values in selected groups of mammary carcinomas, however, can be used to predict patients with high risk of recurrence and they imply considerable prognostic information. Serial CEA determination in the follow-up of patients with operated breast cancer are highly sensitive in early detection of recurrences and are also useful in controlling therapy in individual cases. The biological basis of tumor marker measurements reflecting tumor growth is pointed out and newly developed methodologies for the potential establishment of more specific tumor markers for serodiagnosis and for immunolocalization of tumors are discussed.

Adult↗
PubMed1984

Cell fusion responsible for horizontal oncogenesis by human tumors in nude mice.

Human tumor xenotransplants derived from 4 different carcinomas were established in athymic mice and maintained by serial passage. In vivo human/mouse cell fusion and induction of neoplastic growth of adjacent mouse tissue was investigated in serial passages by isoenzyme analysis, by chromosome analysis and by cloning of induced tumorigenic mouse cells. In 2 xenotransplants human/murine hybrid isoenzyme complexes of pyruvate-glutamate transaminase, glucosephosphate isomerase and mitochondrial malate dehydrogenase were detected. Metaphases containing human and murine chromosomes were found in the first in vitro passage of excised xenotransplants. Cloning of induced mouse tumor cells yielded tumor cell lines tumorigenic in athymic as well as in immunocompetent mice.

Animals↗
PubMed1984

[Clinical significance of the circulating tumor-associated antigen CA 19-9 in cancers of the digestive tract].

The relevance of the tumour associated antigen CA 19-9, defined by a monoclonal antibody, was investigated in 471 patients with carcinomas of the gastrointestinal tract and in 100 patients with benign diseases of the abdomen. In the early stages of gastric and colorectal carcinomas the sensitivity of the CA 19-9 test was between 10 and 25% and increased to about 50% in tumour stage IV. Detection rate in pancreatic carcinoma was 88% and thus markedly higher. The specificity of the test, as against the group of benign abdominal diseases, was 95%. Postoperative CA 19-9 follow-up showed unaltered individual baseline values in 192 out of 196 cases without clinical evidence of tumour progression. However, in 40 out of 61 cases (66%) with recurrencies or metastases continuous increases of CA 19-9 were observed which preceded the clinical relapse by up to 16 months (median 2 months). Concomitant determination of CEA increased sensitivity to 90% due to partial complementary information. This was particularly pronounced in gastric carcinomas in whom continuous increases of CEA involved only 58% of all patients with tumour progression. By simultaneous determination of both tumour markers this ratio rose by increases of both or one antigen to 83%.

Adult↗
PubMed1984

Immunotherapy of tumor-bearing mice with chemically modified tumor membrane fractions of two syngeneic tumor cell lines.

The effects of chemical modification on the immunogenicity of plasma membrane fractions of virus-induced and chemically induced tumor cell lines were tested in syngeneic tumor-bearing mice. The immunotherapeutic effects were dependent on (1) the chemical nature of the modifying reagent, which also determines the molecular site of modification in the membrane components, (2) the degree of modification, (3) the immunizing dose of modified membranes, and (4) the time schedule of immunization. Best results were obtained when the immunizing membrane samples were modified by methylation or acetylation using immunizing doses of membrane equivalents corresponding to 10(3)-10(4) cells. Up to 30% of the animals remained tumor-free and the observed survival of the animals was different from that of the control when immunotherapy was started five days after tumor transplantation. A delayed start of immunotherapy, or simultaneous immunization with tumor transplantation, or immunizations with nonmodified membrane samples led to reduced observed survival. The therapeutic effects were specific for each individual cell line. Cross-protection was not observed when mice bearing chemically induced tumors were treated with modified membrane samples derived from a syngeneic virus-induced tumor cell line.

Animals↗
PubMed1983

In vivo induction of neoplastic growth in nude mouse connective tissue adjacent to xenografted human tumors.

Induction of neoplastic growth of murine stroma cells within the human tumor xenograft was observed after serial passage of CEA and beta 2-microglobulin producing human colonic SLu tumor xenografts in nu/nu BALB/c mice. Mouse tumors within the human tumor xenografts were identified using specific immunohistologic staining techniques for mouse histocompatibility marker or human CEA. These mixed tumors could be distinguished from normal human tumor xenografts by a different relationship between development of the tumor marker in the serum and tumor size. We were able to establish transformed murine cells from human xenografts, either induced by SC injection of 1 X 10(6) tumor cells of the SLu cell line or by human SLu or mammary carcinoma tissue serially passaged in athymic animals. The established human and murine cell lines were characterized by cytogenetic methods. Transformed murine cells were then continuously passaged in tissue culture. The transformed mouse fibroblasts proved to possess tumorigenicity in nude mice. In the case of SLu-derived mouse tumor cells, tumors also developed in the immunocompetent BALB/c mice using 1 X 10(6) to 5 X 10(6) tumor cells for SC transplantation.

Adenocarcinoma↗
PubMed1983

Prognostic significance of preoperative carcinoembryonic antigen in stomach and colorectal cancer.

Prognostic parameters of patients with stomach and colorectal cancer, which could be established within a few days during hospitalization of patients for primary treatment, were characterized and compared in a clinical investigation with observed postoperative survival. Statistical analysis was based on data from a long-term follow-up study of 563 colorectal and 390 stomach cancer patients registered since 1974. The potential prognostic parameters included resectability, tumor extension, and preoperative serum CEA levels. Statistical examination revealed that each of the parameters was associated with highly significant differences in survival of the patients. Combinations of clinical parameters with distinct ranges of preoperative serum CEA levels gave additional valuable prognostic information, thus facilitating the management of patients for adjuvant postoperative treatment.

Carcinoembryonic Antigen↗
PubMed1983

Circulating carcinoembryonic antigen (CEA), a growth parameter in malignant disease.

In a series of experiments we measured tumor volume or tumor mass together with the serum CEA concentration in human adenocarcinoma-bearing nude mice. We observed a linear relationship between log CEA and time over a period of up to 30 days after transplantation of the tumors. In all experiments tumor mass-volume correlated well with concomitant increase of the circulating CEA concentration. A marked dissociation became evident when tumor growth rate slowed down. At that time histologic investigations indicated that necrosis of the tumor could be a potential factor for this phenomenon. A retrospective analysis of the CEA time courses in 114 patients with recurrent colorectal cancer gave evidence for similar CEA developments in 87 cases also exhibiting linear log CEA development with time. Individual CEA doubling times calculated from linear log CEA increases correlated well with observed survival in 36 patients with untreated visceral metastasis. Moreover, the CEA doubling time represented an objective parameter to rate the effect of various postoperative therapies when survival is expressed in multiples of individual CEA doubling times.

Animals↗
PubMed1982

Prognostic value of preoperative serum CEA level compared to clinical staging: II. Stomach cancer.

In a clinical investigation of postoperative survival after primary surgery for stomach cancer, 390 patients were registered since 1974. The potential prognostic parameters examined within the first days of hospitalization for primary resection included age of the patients, operability, tumour extension (TNM classification) and tumour stages I-IV (UICC). Statistical treatment of the data revealed that each of the clinical parameters covers critical ranges associated with highly significant differences in patient survival. The preoperative serum CEA concentration exhibited prognostic significance in addition to the criteria of operability and tumour extension. In selected subgroups of patients with distinct resectability and tumour extension, ranges of preoperative CEA concentration could be specified which were associated with statistically significant differences in the patient survival. The results indicate that the preoperative serum CEA level can be an independent prognostic parameter in stomach cancer.

Aged↗
PubMed1982

Doubling time of circulating cea and its relation to survival of patients with recurrent colorectal cancer.

In a retrospective study the postoperative time courses of CEA in colorectal cancer patients with recurrent disease were analysed. In 87/114 cases with increasing concentrations of circulating CEA under close follow-up a linear relationship between log CEA and time could be established during disease recurrence. The individual doubling times of the serum CEA concentration in the log CEA period were calculated and found to cover distinct ranges dependent on the diagnosis of disease recurrence. The CEA doubling times concomitant with local recurrence or second primary carcinomas ranged from 142 to 868 days, visceral metastasis other than liver metastasis from 47 to 231 days and liver metastasis from 10 to 102 days. Patients with bone metastases exhibited CEA doubling times of 54-60 days and a patient with brain metastasis had a CEA doubling time of 598 days. The CEA doubling times of patients with liver metastasis and no further treatment, correlated well with the time of survival after the initial CEA increase of the log CEA phase (r = 0.870, n = 33). The mean survival expressed in multiples of the individual CEA doubling times was 7.0 +/- 1.8. Patients with liver metastasis who underwent various treatments of recurrent disease had a distinctly longer mean survival of 17.4 +/- 9.4 CEA doubling times (P less than 0.001). CEA doubling times can be used as a potential method to assess the efficacy of various treatments.

Carcinoembryonic Antigen↗
PubMed1982

Growth of human colonic adenocarcinoma and development of serum CEA in in athymic mice. I: Strict correlation of tumour size and mass with serum CEA concentration during logarithmic growth.

The secretion of CEA into the blood of athymic mice was studied with 4 sublines of human colonic adenocarcinoma cell lines, HT 29 and SLu. Growth curves based on tumour volume (caliper measurements) or tumour mass (weight) correlated with a concomitant increase of serum CEA during the logarithmic growth phase, but showed a marked dissociation when the growth rate slowed down. In the logarithmic growth phase doubling times between 2 and 6 days were calculated and about 6-7 doubling times passed until the shift in the growth rate was observed, independently of the sublines transplanted. Constant increases of CEA between 0.03 and 0.45 microgram/l serum per mm3 increase of tumour volume, depending on the sublines, were recorded during the logarithmic growth phase. Sublines releasing high amounts of CEA in vitro (cell culture) retained this characteristic in vivo. Correlation between tumour volume and tumour mass or serum CEA showed correlation coefficients of 0.820-0.977 during the logarithmic growth phase.

Adenocarcinoma↗
PubMed1982

Preferential induction of cell-mediated immunity by chemically modified carcinoembryonic antigen.

Modification of carcinoembryonic antigen (CEA) with various chemicals was investigated. Modification of CEA with dimethylsulfate or acetic anhydride resulted in derivatives which preferentially induced delayed-type hypersensitivity (DTH) against native CEA in mice. The strength of the DTH reaction was dependent on the number and chemical nature of modifying groups as well as on the immunizing dose. The strongest DTH reaction without detectable formation of antibodies was achieved by low dose immunization using heavily methylated CEA.

Acetates↗