Jerome S. Nisselbaum

Estrone and estradiol content in human breast tumors: Relationship to estradiol receptors

Abstract We have measured the estradiol receptor content together with the endogenous estrone and estradiol concentrations in human breast tissue cytosols. There was no evidence for a relationship between high estrogen levels and low receptor measurements. Receptor positive tumor cytosols contained a statistically significant greater estradiol concentration than those of receptor negative tumors or of normal tissue. This was confirmed in a study of sixteen pairs of tumor and normal tissue from the same breast in which the estradiol but not estrone concentration of the receptor positive tumors exceeded that of its normal partner. The results indicate that (a) false negative receptor assays due to the presence of endogenous estrogens are not likely; (b) receptor positive tissues retain greater amounts of estradiol than receptor negative tumors.

The value of diagnostic aids in detecting pancreas cancer.

By contract with the National Cancer Institute, the accuracy of diagnostic techniques was assessed in 184 patients suspected of having pancreas cancer. Of 138 patients who were operated upon, 89 were found to have pancreas duct cancer, 30 had cancer of a different site of origin in the head of the pancreas region and in 19 there was no evidence of cancer at operation. All of the 46 patients who were not operated upon, 13 proven to have cancer and 33 patients discharged as free of cancer, were followed in our clinic. The majority of our patients presented with signs and symptoms of biliary obstruction. Computerized transaxial tomography (CTT) gave a “correct” diagnosis in 31 of 33 patients (94%) with proven cancer, there were 2 patients with a false negative report and a false positive diagnosis occurred in 8 of 20 patients (40%) without cancer. Celiac angiography (CA) gave a correct diagnosis in 78 of 94 patients (83%) with cancer, a false negative in 17%, and a false positive in 32%. 75Sele‐nomethionine pancreas scan correctly diagnosed 27 of 36 patients (75%) with cancer, gave a false negative in 25% and a false positive in 31%. Ultrasonog‐raphy gave a correct diagnosis in 18 of 27 patients with cancer (67%), a false negative in 33% and a false positive in 28%. Endoscopic retrograde cholangio‐pancreatography diagnosed correctly 8 of 11 cases (73%) of cancer, there were false negative diagnoses in 3 cases (27%) and false positives in 3 of 14 patients (21%). Duodenal aspiration techniques gave a very low percentage of correct diagnoses. Chronic pancreatitis most commonly gave rise to a false positive diagnosis. Serum alkaline phosphatase was elevated in 82% of patients, gave 18% false negatives and 33% false positives. Carcinoembryonic antigen (CEA) was elevated (> 2.5 ng/ml) in most of the pancreas cancer patients but also in patients with other cancers and with non‐cancerous diseases. In our hands, CTT, CA, alkaline phosphatase, 75Se‐methionine and ultrasonography, in descending order, have given the highest percentage of correct diagnoses but false positive and false negative diagnoses prevented any single test from being conclusive.

Serum tumor marker decline is an early predictor of treatment outcome in germ cell tumor patients treated with cisplatin and ifosfamide salvage chemotherapy

Background. Serum tumor marker regression (alpha‐fetoprotein [AFP] and human chorionic gonadotrophin [hCG]) was studied in patients treated with ifosfamide‐based chemotherapy for cisplatin‐resistant germ cell tumors (GCT) to investigate the role of marker regression as a predictor of treatment outcome.

Serum tumor markers in patients with metastatic germ cell tumors of the testis: A 10-year experience

The serum values of alphafetoprotein, human chorionic gonadotropin, lactate dehydrogenase, and carcinoembryonic antigen in patients with metastatic testicular cancer were reviewed for the period 1972 to 1982. All values were obtained before chemotherapy was begun. Elevated values of alphafetoprotein were present in 47 percent of patients tested, of human chorionic gonadotropin in 60 percent, of lactate dehydrogenase in 64 percent, and of carcinoembryonic antigen in 11 percent. The frequency of elevated values of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase decreased during the study period. Inverse relations between elevated values of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase and both complete remission rate and survival rate were noted in some of the chemotherapy trials. Carcinoembryonic antigen was believed not to be useful as a marker in this disease. It is concluded that assays of alphafetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are important both clinically and prognostically in patients with testicular cancer.

Estrogen receptor protein in lesions of the male breast. A preliminary report

Eleven specimens of breast lesions obtained from 10 male patients were analyzed for estrogen receptor protein (ERP). Three patients (ages 49, 77, 82 years) had infiltrating duct carcinomas with no axillary metastases. ERP in each of these was positive. Eight specimens with gynecomastia, one of which was obtained from the 77‐year‐old patient with carcinoma in the same breast, were also analyzed. Of these ERP was positive in a 59‐year‐old man who had cirrhosis of the liver; two patients with borderline ERP had hepatitis and testicular seminoma, respectively. No relationship between histopathologic features of the lesions and ERP results was found and it is too early to relate these ERP studies to prognosis in these patients. Review of available literature, including our cases, reveals that six of eight male breast carcinomas were ERP‐positive.

Interrelationships of histopathology and other clinical variables in patients with germ cell tumors of the testis

Possible relationships between histopathologic cell type and several clinical variables were examined in 253 patients with Stage III nonseminomatous germ cell tumors of the testis. No statistically significant associations were found between cell type and either the side of primary tumor or cryptorchidism. The presence of elements of choriocarcinoma was associated with the presence of retroperitoneal tumor (P < 0.03) but no other association between cell type and site of metastasis was encountered. Elevated serum levels of human chorionic gonadotropin were found in patients with elements of choriocarcinoma but serum levels of alphafetoprotein, lactate dehydrogenase and carcinoembryonic antigen were not correlated with a specific cell type. No statistically significant association was found between cell type and either complete response to combined modality therapy or survival. These results would indicate that cell type is probably not an important prognostic variable in patients with Stage III nonseminomatous tumors of the testis.

Correlation of serum tumor markers and lymphangiography with degrees of nodal involvement in surgical stage II testis cancer.

There were 60 patients at our cancer center who underwent serum tumor marker studies (beta subunit of human chorionic gonadotropins and alpha-fetoprotein) and pedal lymphangiography before retroperitoneal lymph node dissection. Surgical stage II cases were divided according to tumor, node and metastasis staging. Beta-human chorionic gonadotropin and/or alpha-fetoprotein was elevated in 9 per cent (1 of 11) and the N1 cases, 36 per cent (5 of 14) of the N2A cases, 50 per cent (13 of 26) of the N2B cases and 89 per cent (8 of 9) of the N3 cases. Lymphangiography was positive or suspicious in 9 per cent (1 of 11) of the N1 cases, 36 per cent (5 of 14) of the N2A cases, 46 per cent (12 of 26) of the N2B cases and 56 per cent (5 of 9) of the N3 cases. Serum tumor markers and lymphangiography combined suggested lymph node metastases in 18 per cent (2 of 11) of the N1 cases, 50 per cent (7 of 14) of the N2A cases, 73 per cent (19 of 26) of the N2B cases and 100 per cent (9 of 9) of the N3 cases. We conclude that tumor markers and lymphangiography measurements are equally effective in the diagnosis of retroperitoneal lymph node metastases and that diagnostic accuracy is enhanced significantly by combining these 2 modalities. Retroperitoneal lymph node dissection remains the most reliable staging procedure. Reports of the accuracy of clinical staging should be correlated with subcategories of stage II disease.

THE SYNTHESIS AND REGULATION OF ASPARTATE AMINOTRANSFERASE ISOZYMES

ABSTRACT: The rate constants of synthesis and degradation of aspartate aminotransferase (AAT) isozymes in red blood cells were studied during induction of and recovery from phenylhydrazine-produced reticulocytosis. The increase in total AAT activity during the induction of reticulocytosis was due primarily to the 47-fold increase in the activity of the mitochondrial isozyme (K S = 0.131; K d = 0.015; t 1/2 = 45 hr). The activity of the cytosolic isozyme increased to about 3 times its control value (K S = 0.036; K d = 0.017; t 1/2 = 48 hr). The rate constants following recovery from phenylhydrazine treatment were: K S = 0.005; K d = 0.028; t 1/2 = 25 hr. for the mitochondrial isozyme and K S = 0.0043; K d = 0.0044; t 1/2 = 155 hr. for the cytosolic isozyme.

The Kinetics of Synthesis and Degradation of Aspartate Aminotransferase Isozymes in Rat Peripheral Red Blood Cells During Cytodifferentiation

Summary The kinetics of synthesis and degradation of aspartate aminotransferase (EC 2.6.1.1) isozymes were investigated in peripheral red blood cells of rats made reticulocytotic with phenylhydrazine. Immunochemical studies showed that reticulocytes contain predominantly the cationic isozyme, whereas mature erythrocytes contain only the anionic isozyme. Following initiation of phenylhydrazine treatment, the cationic isozyme increased 47-fold above its control level on Day 5, and the anionic isozyme increased threefold above its control level on the 8th day. The half-lives were 24.6 and 154.9 hr for the cationic and anionic isozyme, respectively. The faster turnover of the cationic isozyme appears to be related to its rapid rate of degradation. We thank Miss Frances Grainger for her excellent technical assistance.