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Biomedical subjects

R Lamerz

Publications and source records attributed to R Lamerz.

117 records · Page 7Linked to original sources

Clinical relevance of tumor markers for the control of chemotherapy.

This presentation is based on our experience with tumor marker monitoring of surgery therapy and chemotherapy effects. The control of chemotherapy is one of the most important problems in oncological practice. The correlation between the clinical status of the patient and tumor size changes, based on the results of different imaging methods, has been the most important and most frequently used method. However, the therapy effect has been recently assessed by markers of the biological activity of the tumor. Using tumor markers for the assessment of the effect of surgery therapy is already part of routine practice in many different types of cancer. Pre-operative and post-operative values of tumor markers are essential for a proper evaluation. However, tumor marker monitoring of the effect of radiotherapy and chemotherapy has been used very rarely, mostly only for research purposes. Besides monitoring by classical tumor markers, monitoring by markers of angiogenesis and apoptosis seem to be promising for the assessment of chemotherapy effect. Measurement of circulating cancer cells by means of mRNA also seems to be intriguing for therapy effect control and monitoring of the course of disease. Unfortunately, the routine use of these methods has been applied in only a few institutes worldwide. A completely different situation has been observed in palliative treatment. In most cases, changes of serum levels of tumor markers correlate with therapy effect. Thus, the effect of treatment on tumor proliferation can be successfully estimated by decreasing tumor marker levels.

Antineoplastic Agents↗

Serum marker combinations in human breast cancer (review).

Breast cancer markers (TM) are mainly useful for monitoring the course of disease after diagnosis and first line treatment with the control options of primary treatments early recognition of reactivation and efficiency control of palliative treatment. The best single and established marker is a polymorphic epithelial mucin of the MUC-1 family the prototype of which is CA 15-3 (successive markers: MCA, CA-549, TAG-12, CAM 26/29) followed by CEA with lower diagnostic sensitivity and specificity and TPA/TPS reflecting more the proliferative activity. Besides former TM combinations of CEA with one or more less specific markers (e.g. PAM, CRP, beta 2m, ferritin, GCDFP, HCG, total or boney AP, gamma GT), more recent studies recommend the use of fewer markers such as TPA/TPS + CEA or CA 15-3, CA 15-3 + CEA or MCA, CA M26 + CA M29, TAG12 + CA 15-3 + MCA and CEA + CA 15-3 + ESR.

Antigens, Tumor-Associated, Carbohydrate↗

AFP isoforms and their clinical significance (overview).

AFP has maintained great clinical relevance as target tumor marker of germ cell tumors (YST = yolk sac tumors) and hepatocellular cancer (HCC) besides its occasional elevation in other malignancies. Its organ and tumor specificity is further limited by elevation in benign liver diseases (BLD) and in pregnancy. The binding of various lectins to its carbohydrate chain (5%) in addition to mere isoelectric focussing has been successfully used in the differentiation of AFP source and disease. The primarily used lectins in affinity electrophoresis and chromatography are Concanavalin A and lens culinaris agglutinin (LCA). The inclusion of other lectins (e.g. erythroagglutinating E-PHA, allomyrina dich. aggl. A lectin) and a more practical nomenclature have been used for characterization of 4 reactive patterns of cord serum/liver/BLD, HCC, g.i. tumor and YST type. In particular, data are reviewed concerning the clinically important liver AFP differentiation by means of LCA and E-PHA differentiation. In conclusion the investigation of AFP lectin binding in cases unexplained AFP elevation may be helpful in the differentiation of AFP source and malignancy.

Chromatography, Affinity↗

Biliary mucin secreted by cultured human gallbladder epithelial cells carries the epitope of CA 19-9.

Serum CA 19-9 is increased in patients with different gastrointestinal malignancies. Unfortunately, CA 19-9 is also detected in high concentrations in normal bile causing unspecific serum elevations during inflammatory disease of the biliary tract and cholestasis. In order to identify the source of CA 19-9 in bile, the capacity of cultured human gallbladder epithelial cells (HGBEC) to secrete CA 19-9 was investigated. Cells were harvested from gallbladders removed by cholecystectomy and cultured for up to 14 days in collagen I coated 24-well culture dishes. CA 19-9 was measured in the culture medium by a solid-phase CA 19-9 EIA (Boehringer). In addition, culture medium was separated by Sepharose 4B-Cl, Concanavalin-A (Con-A) and CA 19-9 affinity chromatography. Significant CA 19-9 activity was measured in the culture medium after a 24 hour incubation period. Following separation of the culture medium by Sepharose 4B-Cl and Con-A affinity chromatography, 90% of the CA 19-9 activity was recovered in the exclusion volume (> 2000 kDa) from which 90% were identified as Con-A negative. A close correlation was found between CA 19-9 and concentrations of mucin purified from human gallbladder bile. Furthermore, CA 19-9 affinity chromatography selectively extracted mucins from the culture medium of HGBEC. Finally, addition of the mucin secretagogue bethanechol (6 mM) to the culture medium increased CA 19-9 activity in the medium. In conclusion, normal HGBEC secrete mucins carrying the epitope of CA 19-9. During inflammatory biliary disease unspecific elevation of CA 19-9 in serum may reflect both inflammatory hypersecretion and leakage of biliary mucins into serum.

Bethanechol↗

Screening for prostatic carcinoma with prostate specific antigen.

The usefulness of prostate specific antigen (PSA) in screening for prostatic carcinoma was studied in 262 inpatients of the department of internal medicine. All patients underwent a rectal digital examination and determination of PSA by the Tandem-E method (Hybritech). The plan was to perform biopsies if there were suspicious findings on the rectal examination or if the PSA value was more than 10 ng/ml. The PSA values were < or = 4 ng/ml in 219 patients (83.6%), > 4 to 10 ng/ml in 27 patients (10.3%) and > 10 ng/ml in 16 men (6.1%). In consideration of the severity of disease which limited life expectancy we did not perform a biopsy on 37.5% of the patients with PSA > 10 ng/ml. 7 patients with prostatic carcinoma were found. Their PSA values varied between 11.2 and 875 ng/ml. The cancer detection rate was highest for the combination of a suspicious rectal examination and a PSA value > 10 ng/ml (70%).

Aged↗

Is serum tumor marker half-life a guide to prognosis in metastatic nonseminomatous germ cell tumors?

BACKGROUND: The value of serum tumor marker kinetics of AFP and HCG assessed by marker half-life (MHL) analysis for diagnosis and in the follow-up of patients with nonseminomatous germ cell tumors (NSGCT) is still debated controversally. The aim of this retrospective study was therefore to investigate the influence of serum MHL during the first two cycles of chemotherapy on the long-term outcome in metastatic NSGCT. MATERIAL AND METHODS: 147 patients with at least 2 abnormal marker values > 7 days after start of chemotherapy were investigated for HL analysis (HL cut off 3.5 days for HCG and 7 days for AFP). HCG and AFP determinations were performed by a double monoclonal IRMA (HCG) and conventional RIA (AFP) developed by our laboratory. RESULTS: According to these cut offs 35/108 patients (32.4%) had a prolonged HCG HL and 41/114 patients (36%) a prolonged AFP HL. Patients with either MHL prolonged had a significantly inferior overall survival (OS; 10 year OS 37% vs. 75%, p = 0.0005) and progression-free survival (PFS; 10 year PFS 29% vs. 69%, p < 0.0001) than those with a prolonged HCG MHL (OS; 10 year OS 36% vs. 65%, p = 0.003; 10 year PFS 28% vs. 56%; p = 0.001) and even more than those with a prolonged AFP MHL (10 year OS 39% vs. 70%, p = 0.02; 10 year PFS 32% vs. 56%, p = 0.01). CONCLUSION: The remarkable prognostic information assessed by MHL analysis in this retrospective study merits further confirmation by a prospective study for its appropriateness in selecting patients for high dose chemotherapy.

Biomarkers, Tumor↗

Value of HAMA--determination in clinical practice--an overview.

HAMAs (human anti mouse antibodies) in serum of patients may be stimulated as an immunologic reaction to the application of animal protein. They are differentiated into heterophilic (species-unspecific) and mouse-specific anti-isotypic (often IgG1) or-idiotypic antibodies as well as according to the human immunoglobulin type (IgG or IgM). Besides infrequent clinically immunologic side effects (anaphylactic reaction), their influence on tumor marker measurements predominates in the follow-up of tumor patients by the possible impairment of newly applied monoclonal antibodies. The detection of HAMAs is performed on suspicion of a tumor by self-made or commercial tests, however, there is no consensus standardization of tests, standards and controls. Experiences are reported herein on the occurrence of heterophilic antibodies, reasons of suspicion, detection and removal, comparative determination of HAMAs by two commercially available tests (ImmunoSTRIP HAMA, Enzygnost) and HAMA induction in patients following immunoscintigraphy (OC-125, n = 27). Besides the rare appearance of HAMAs in patients without pretreatment or following biologic therapy, i.v. application of monoclonal antibodies for diagnosis (immunoscintigraphy) or therapy represents the most frequent reason for HAMA development that should always be ruled out in case of anamnestic indication and clinically unexplained tumor marker changes.

Animals↗