Detection of serum-blocking factors by inhibition of allorosette formation in rats with long-surviving renal allografts following short-term postoperative ALS treatment.

Thirty-nine (LEW x BN)F1 kidneys were transplanted to LEW rats. Twenty-four untreated recipients survived for a mean time of 16.1 +/- 1.7 days (group 1). Fifteen recipients received 4 ml of antilymphocytic serum per rat (group 3). In the last group 10 recipients survived for more than 4 months. The spleen cells of these permanently surviving 10 rats were obtained by splenectomy and used in a graft-versus-host assay, and this assay showed that the reactivity of these cells was normal. Following splenectomy the animals were given an (LEW x BN)F1 skin allograft, followed 18 days by a second. After another 18 days (LEW x Buf)F1 "third party" skin allografts were transplanted to the same animals. Animals of group 2 rejected their first grafts with a mean survival time of 12.2 +/- 1.2 days, whereas the second grafts were rejected normally as were the third party grafts. Attempts were made to detect lymphocytotoxic antibodies and haemagglutinins before and after the transplantation of skin grafts and none could be found up to day 53. The sera of group 2 inhibited allorosette formation by 38%. This serum-blocking factor was donor specific. It is probable that the survival of the kidney transplants following antilymphocytic serum treatment was brought about by the development of blocking antibodies.

Imaging of brain tumors with L-3-[123I]iodo-alpha-methyl tyrosine and SPECT.

Carbon-11-labeled amino acids have been successfully used to image brain tumors by PET. This study was undertaken to evaluate the potential of L-3-[123I]-iodo-alpha-methyl tyrosine (123IMT) for metabolic imaging of brain tumors. Ten patients (glioblastoma, oligodendroglioma, lymphoma, and metastases) had early and delayed brain SPECT with a rotating gamma camera after i.v.-injection of 200-300 MBq 123IMT. In nine patients the tumors showed intense uptake of the radiotracer. Tumor-to-brain tissue ratios were between 1.4 and 2.6. 123IMT shows potentials for monitoring the effects of brain tumor therapy.

Measurement of Tennessee antigen, carcinoembryonic antigen, tissue polypeptide antigen and alpha-feto-protein in body fluids associated with pregnancy.

The aim of this study was to establish if the oncofetal antigens alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), tissue-polypeptide antigen (TPA), and Tennessee antigen (TAG) were present in body fluids associated with pregnancy. There antigens were measured in amniotic fluid, cord blood, and semen. In contrast to AFP, CEA, and TPA, which were found in high concentration in amniotic fluid, the TAG concentration was lower than observed in serum. In cord blood, AFP was elevated in all samples examined. CEA was elevated in 35% of the samples. TAG was normal in all 20 samples studied. Examination of semen demonstrated that TPA, CEA, and TAG were increased over normal serum values; AFP was not increased over normal serum values in the 103 samples of semen studied. The lack of increased concentrations of TAG in amniotic fluid, cord blood and serum of pregnant women provides further evidence that this antigen is distinct from CEA, AFP or TPA. The lack of AFP in semen is interesting, and requires further investigation.

Proteomics as a tool for detection of nuclear matrix proteins and new biomarkers for screening of early tumors stage.

Nuclear matrix proteins are involved in control and co-ordination of gene expression. They have been isolated by extraction procedures, followed by gel electrophoresis and matrix- or surface-enhanced laser desorption, and ionisation, with direct detection of retained proteins by time-of-flight mass spectrometry. Some nuclear matrix proteins from tumor tissues demonstrated tumor-specific expression which led to the development of highly tumor-specific nuclear matrix protein assays. In bladder cancer, NMP22 is twice as sensitive as cytology in detecting early stage cancers, and up to 90% sensitive and 99% specific. NMP179 in squamous intraepithelial cervical lesions detects high-grade lesions with 96% sensitivity. Recently new technological approaches using ProteinChips, tracer-free biomolecular interaction, mass spectroscopy and nanotechnology have helped to successfully identify, and apply specific biomarkers for cancer of the prostate, breast and colon and to develop new approaches for simultaneous screening of early cancer with several new biomarkers.

Computer modeling of cytokeratin release in clinical oncology.

The levels of cytokeratins (CK) in serum of cancer patients have been widely used for monitoring progression of cancer growth and the effectiveness of cancer treatment. Previous studies have shown that the release of CK by tumors in patients is a complex process which depends on the rate of cell damage caused by an increasing tumor mass, or by the tumor treatment, but is not in any simple manner correlated to the number of proliferating cells or to the total tumor mass (1). The complexity of the CK-releasing process has been analyzed by a computer model which mimics the progress of tumor growth, allows the introduction of different types of treatment (i.e. irradiation, chemotherapy and surgery), and computes the amount of CK released by the tumor, and the level of CK in blood and blood clearance. The computer model can be used to obtain a better understanding of the interactions of various factors, for scheduling of treatment and CK sampling, and for analyzing the effects of treatment.

Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.

Serum TPS versus TPA in Egyptian bladder cancer patients.

This study included 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract diseases and 70 healthy controls). Serum TPA was determined using the Prolifigen TPA IRMA kit supplied by AB Sangtec Medical, Bromma, Sweden and serum TPS was determined using the TPS IRMA kit supplied by Beki Diagnostics AB, Bromma, Sweden. The results of this study revealed that serum TPA had better sensitivity than serum TPS while no marked difference was found in the false-positivity rates in the non-malignant urinary tract diseases. A correlation coefficient of 0.83 was found between serum TPA and TPS. No relation was found between either TPA or TPS and histopathological stage, grade or association of the tumor with bilharziasis. As regards the histopathological type of the tumor, serum TPS was slightly higher in squamous cell than transitional cell carcinoma but TPA showed no difference. In the follow-up of bladder cancer patients after surgery both TPA and TPS showed an excellent concordance with the clinical state of the patients. In conclusion, TPS does not seem to be an optimal test in Egyptian patients with bladder cancer but serial determinations of one of the two markers can be used in the follow-up of these patients after surgery.

Clinical results of immunoscintigraphy in a variety of malignant tumors with special reference to immunohistochemistry.

Radioimmunoscintigraphy was performed in 52 patients with a variety of malignant tumors (colorectal, melanoma, lung, testicular, ovarian, bladder, carcinoid). Respective antibodies or their F(ab')2 fragments against CEA (n = 23), melanoma antigen 225.28 S (n = 18), TPA (n = 4), beta HCG (n = 5) and HMFG2 (n = 2) were selected by immunohistochemistry of the primary tumor. Most patients were suspected of recurrence or of hitherto unknown distant or local metastases. Overall accuracy was 61% (32/52). False negatives amounted to 33% (17/52). Useful additional clinical information-not available by CT, ultrasonics or serum levels of tumor markers-was obtained in 17 out of 52 patients (= 33%). From these results it seems obvious that antibodies used for radioimmunoscintigraphy should be selected on the basis of immunohistochemistry.

The role of nuclear medicine in oncology.

Nuclear Medicine offers screening methods for oncology such as bone and bone marrow scintigraphy. During the last two decades, special procedures have gained widespread application. This paper is centered around the "tumor-specific" radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a significant role. Ga-67 still has its indications in lymphoma, while in other diseases Tl-201 chloride is now the agent of choice. Especially in thyroid cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical. More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may also be used for tumor scintigraphy, especially in brain lesions. In addition, I-123 IMP has successfully been used for imaging malignant melanoma. Another promising field of tumor diagnosis is receptor imaging. In neuroblastoma and malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice and may be considered as a receptor imaging agent also. First clinical results with In-111 octreotide show potentials as somatostatin-receptor radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung cancer, while I-123 estradiol needs some improvement until it may be recommended as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal tumor antibodies and their fragments have gained widespread application. Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I-131 labeled OC-125 antibodies have proven to be of clinical significance in melanoma, colorectal and ovarian cancer.

[Significance of biological markers for the diagnosis of urinary bladder cancer]. / Bedeutung von biologischen Markersubstanzen für die Diagnose des Harnblasenkarzinoms.

Several substances are discussed which possibly may play a role as biological markers in urinary bladder cancer, such as the carcinoembryonic antigen, some proteins, amino acids and their metabolites as well as enzymes. The significance of these serum and urine measurements for the diagnosis of bladder cancer is critically reviewed.

[Analysis of tumor markers in lung biopsies and in bronchial lavage]. / Analyse von Tumormarkern in Lungenbiopsien und in der Bronchiallavage.

The aim of this study was to conduct immunohistochemical examinations of cell and tissue material compared with clinical examinations of markers to discover the possible mechanisms that can result in marker concentration increases in the plasma and other body fluids. From cell material and biopsies it was possible to identify in small-cell carcinomas TPA (52% of the carcinomas), NSE (57%) and no CEA. Of the non-small cell carcinomas (squamous cell and adenocarcinomas) 88% were TPA-positive, 52% CEA-positive and in metastases 100% TPA-positive and 66% CEA-positive. NSE was not found. Marker examinations in tissue and cell material can yield satisfactory results in recognising neuroendocrinal differentiations, and in diagnosis and differential diagnosis of metastases and lymphomas, compared with clinical tumour marker studies.

Significance of plasma tissue polypeptide antigen determination for diagnosis and follow-up of urothelial bladder cancer.

Plasma concentrations of tissue polypeptide antigen (TPA) were determined in 104 patients with all stages and grades of urinary bladder cancer. Patients with evidence of bacterial or virus infections were excluded. In addition, follow-up controls after treatment were performed. At a rate of 5% false positive values, the diagnostic sensitivity for the tumour stage pTis/pT1 was 63% and for the stages pT2-4 it was 76%. Patients with proved lymph node or distant metastases showed elevated values in 100% of cases. A positive correlation was found between the 3 grades of malignancy and the TPA concentrations. Except for the tumour diagnosis, TPA is a valuable parameter for follow-up controls. Our results show a very good correlation of the plasma TPA concentration with tumour progression as well as with stabilisation and regression after treatment.

Specificity and sensitivity of human chorionic gonadotropin radioimmunoassays. A comparison of two different approaches.

Two different procedures for determination of HCG in plasma from patients with testicular germ cell tumors, patients with benign disease, and normal controls were applied: (1) measurement of the amount of HCG and its beta-subunit, and (2) assay of the isolated beta-subunit alone. The test which measured the free beta-subunit and the HCG molecule gave 13% more sensitivity in patients with nonseminomatous germ cell tumors. The specificity in blood donors was 100% for both tests. In benign diseases the measurement of the complete molecule gave 100% specificity, whereas the other procedure had a specificity of 95%. For these reasons, the determination of the complete molecule seems to be preferable for patients with nonseminomatous germ cell tumors.

Comparison between cell kinetical and immunohistochemical studies on carcinoma and atypia/dysplasia of urinary bladder mucosa.

Results of cell kinetic analyses on transurethrally obtained material from urinary bladder are compared with parallel immunohistochemical tests on carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), performed on the same material. Labelling index increases from 1.4% in slight to 20% in marked urothelial atypia. CEA reaction in slight atypia is slight or moderate, slight, moderate or distinct in atypia, and moderate to distinct in carcinoma in situ. TPA always shows moderate to distinct reactions. Cell kinetically, urothelial carcinomas yield similar gradations. They were positive for CEA in 70% and for TPA in 100%. In GO and GI carcinomas, negative and slightly positive reactions predominate, poorly differentiated lesions yield predominantly distinct reactions. In all grades, TPA ranges from slight to distinctly positive. As in cell kinetic analyses, there is a relationship between differentiation grade and stage for CEA expression. This does not apply for TPA. The results permit us to draw conclusions on the different biological and histogenetical behavior of urothelial carcinomas. There are undoubtedly differences in the behavior of papillary-exophytical and solid invasive carcinomas in terms of both cell kinetics and immunohistochemistry.

Comparison between tissue antigen analysis and plasma determinations for TPA and CEA in transitional cell carcinomas and in tumorfree urothelium of the urinary bladder.

Plasma determinations for TPA and CEA resulted in a sensitivity of 90% and 19-42%, respectively, for urothelial bladder cancer. By immunohistochemical staining TPA was positive in 100% and CEA in about 80% of the cases. The CEA staining in cancer tissue seemed to correlate with the WHO grade. Because TPA resulted in strong positive staining and high sensitivity in the plasma, contrary to CEA, showing less positive staining and a lower sensitivity, there seemed to be a good correlation between staining and plasma sensitivity for both markers.

[Clinical, histological, and immunohistochemical studies of squamous cell carcinomas of the oral mucosa and the prolabium]. / Plattenepithelkarzinome der Mundschleimhaut und des Lippenrots. Klinische, histologische und immunhistochemische Untersuchungen.

In diagnosing and monitoring squamous cell carcinomas of the oral mucosa and the prolabium the carcinoembryonic antigen (CEA) is a frequently used tumor marker. In a pilot study six of these carcinomas with established pathological serum levels of CEA were clinically analyzed and immunohistochemically examined for the tumor antigens CEA and, in addition, TPA (tissue polypeptide antigen). Only in one case could a positive CEA reaction be found. In the same tumors TPA could not be demonstrated. It is concluded from these results that elevated CEA serum levels are no tumor specific reactions and that the use of this tumor marker is to be considered with criticism.