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Biomedical subjects

J A Kellen

Publications and source records attributed to J A Kellen.

At least 37 records · Page 2Linked to original sources

Effects of antibodies to choriogonadotropin in malignant growth. I. Rat 3230 AC mammary adenocarcinoma.

To determine whether the in vivo production of antibodies against choriogonadotropin (CG) could modify the relationship between host and malignant growth, the effects of preimmunization with a conjugate of the beta-subunit of CG and tetanus toxoid (CG beta-tt) on the development and growth of lung metastasis following I.V. injection of R 3230 rat mammary adenocarcinoma cells into Fischer 344 female rats have been investigated. This neoplasm has been previously demonstrated to synthesize CG-like material. A test group of 70 animals and two matched control groups of 15 animals each were used. One of the control groups was untreated and the other received tetanus toxoid only. All the control animals had multiple lung foci of neoplastic cells ten days after seeding, as has been previously observed, and CG antibodies were undetectable. In contrast, a significant titer of anti-CG was found in all preimmunized animals. At the same time, the pretreated animals rarely had a few small neoplastic nodes in the entire lung sections at the standard 8--10 days post-seeding. The protective effects of preimmunization with CG beta-tt were further demonstrated by the animals living 20 days post-seeding, the absence of lung pathology in the ones killed thereafter, and by six animals that were left alive and have not shown any deterioration for more than six months after the administration of the cell suspension.

Adenocarcinoma↗

Effects of antibodies to choriogonadotropin in malignant growth. II. Solid transplantable rat tumors.

We have studied the effects of preimmunization with a conjugate of beta-subunit of choriogonadotropin and tetanus toxoid (CG beta-tt) on the growth of the implanted R 3230 AC mammary adenocarcinoma (in Fischer 344 rats) and the implanted 5123 1-1 hepatoma (in Buffalo rats) after 20 days, in order to determine if the in vivo production of antibodies against CG could modify the relationship between host and malignant growth. The results obtained demonstrated that active immunization against CG retarded significantly (P less than 0.01) the growth of the two transplantable tumors. Anti-CG antibodies were also determined and constantly found in the sera of all the preimmunized rats of both strains while no antibodies to CG were found in the control animals.

Adenocarcinoma↗

Reevaluation of C-reactive protein in cancer sera by radioimmunoassay and radial immunodiffusion. I. Diagnostic value and use in battery of conventional tumor markers.

C-reactive protein (CRP) has been found to be ubiquitous in sera when determined by a highly sensitive methods such as radioimmunoassay. Patients with some tumors appear to have much higher serum levels of CRP than others; in these, CRP seems to reflect the tumor burden. There is a positive correlation with TNM staging and the disease activity a the time of determination. CRP shows a high degree of 'uniqueness' when correlated with other routinely used cancer markers such as carcinoembryonic antigen, placental-like alkaline phosphatase and gamma-glutamyltranspeptidase.

Alkaline Phosphatase↗

Antitumor activity of tilorone hydrochloride on a transplantable rat adenocarcinoma.

Tilorone HCL, administered in drinking water, retarded and slowed significantly the growth of the transplantable R3230 AC rat adenocarcinoma in Fischer 344 rats. This effect is dose-related; from the average three dosage levels studied, daily intake of 30 mg/kg rat/day was found to be optimal. However, Stadie slices of tumors from Tilorone-treated animals when transplanted, took, and showed a growth curve similar to tumors from untreated rats. Exposure to Tilorone does not select tumor cell clones of lesser malignancy or different histopathology.

Adenocarcinoma↗

Alkali-resistant hemoglobin (HbF) in cancer patients.

Elevated levels of alkali-resistant (fetal) hemoglobin were found in patients with cancer, in the absence of any overt hematologic disorders. This phenomenon was observed most frequently in patients with gonadal tumors and appears to reflect tumor burden and activity of disease.

Female↗

Aldolase isoenzyme patterns during human ontogeny and in lung, kidney and breast cancer.

Enzyme patterns characteristic of fetal tissue have been noted in some experimental tumor models, particularly in hepatomas. In this study we undertook to determine whether biochemical evidence of a similar reversion could be detected in tumors of other human organs. As marker, we chose to use the aldolase isoenzymes A, B and C, for which distinct adult and fetal tissue patterns have been described. Using monospecific antibodies, we determined the aldolase isoenzyme pattern in a variety of human organs ranging in age from 14 to 40 weeks of gestation, in the 2- to 3-month postnatal period and in adults. In addition, 19 breast cancers, 19 primary lung cancers and 8 kidney cancers were examined. Our studies on breast cancer revealed three apparently distinct groups -- one showing primarily the A isoenzyme type (6 cases), a second containing mainly A with considerable quantities of B and C isoenzymes (9 cases) and a third group (4 cases) which may contain a different isoenzyme altogether since the combined activity of the three known forms was less than 100% in each case. In lung cancer, fetal characteristics could be substantiated since in fetal and adult lung tissue, the isoenzyme pattern is almost identical; 3 out of 19 cases showed substantial quantities of the B isoenzyme. In kidney tumors, a reversion to the A form with an appreciable fraction of the C form was found, which is similar to the fetal pattern.

Adenocarcinoma↗

Effect of alpha-difluoromethyl ornithine on the transplantable rat hepatoma 5123, 1-1.

Oral treatment with alpha-difluoromethyl ornithine (2.75 g/kg rat/day) simultaneous with subscapular implantation in Buffalo rats of the 5213, 1-1 hepatoma, retarded significantly the tumor growth rate for 20 days. The regimen also decreased tumor ornithine decarboxylase activity (ODC); however, the tumors growing despite treatment, maintained their malignant characteristics and ODC activity when re-transplanted into normal animals.

Animals↗

Detection of tumor antibodies in patients with gastrointestinal carcinomas by a solid-phase radioimmunoassay.

Metastatic tumors from livers of 5 patients with gastrointestinal carcinomas and from the liver of 1 patient with malignant breast carcinoma were extracted with 3 M KCl; similar extracts were prepared from normal human colon and liver and from human fetal gut. The extracts were depleted of serum globulins by passage through reverse immunoadsorbent columns consisting of rabbit antibodies to the F(ab)2 fragment of human IgG and were then coupled to CNBr-activated paper disks. These "antigen" disks were used in a radioimmunoassay, with the aid of 125I-labeled rabbit antihuman F(ab')2 antibodies for the assay of circulating tumor antibodies produced by cancer patients. Statistical evaluation of the results with plasma samples from 47 patients with colorectal carcinomas and from 7 patients with other gastrointestinal disorders (polyps, villous papilloma, diverticulitis, and Crohn's disease) indicated that a significant number of patients had antibodies to cross-reactive tumor antigen(s). The cross-reactive tumor antigen(s) involved in the reaction was not detected in extracts of the gastrointestinal tract from 12-week human fetuses and did not cross-react with carcinoembryonic antigen.

Adult↗

Dynamic changes of serum gamma-glutamyl transferase in chronic alcoholism.

Elevated serum gamma-glutamyl transferase (GGT) levels were found in 29% of 155 chronic alcoholics undergoing detoxification treatment. Alkaline phosphatase (AP) was increased in 16%, alanine aminotransferase--SGPT (ALT) in 12% of the patients, while 23% had elevations of either AP or ALT or both. Of the foregoing parameters, GGT was the best single indicator of liver involvement. In course of the follow-ups GGT/ALT correlation improved, but GGT/AP correlation deteriorated. In 9 patients, abstinence during follow-up was associated with progressive decrease in previously elevated serum GGT. Because of its unique sensitivity, GGT may be useful as a screening and/or monitoring aid in alcoholism.

Alanine Transaminase↗

Carcinoembryonic antigen (CEA) and other tumor markers in ovarian and cervical cancer.

Combinations of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (GGT), pregnancy-associated macroglobulin (PAM) and placenta-like alkaline phosphatase (PLAP) were studied in groups of patients with ovarian and cervical cancer. In ovarian cancer, only CEA and PLAP levels appeared to reflect tumor burden and were complementary in detecting active disease. In cervical cancer, CEA and GGT reflected tumor burden, while PLAP showed just the reverse--the highest degree of positivity being present in minimal disease. PLAP positivity was even more pronounced in patients with cervical dysplasia and carcinoma in situ while CEA and GGT were negative. The data indicate that the use of marker combinations can improve our capacity to detect minimal disease and provide information regarding tumor biology that may not be available by studying individual markers or by other means. It remains to be determined whether the use of tumor markers can influence existing therapy sufficiently to alter the outcome in cancers which are notoriously difficult to treat.

Alkaline Phosphatase↗

Carcinoembryonic antigen in breast cancer.

Carcinoembryonic antigen (CEA) levels were determined in 742 postoperative patients with breast cancer. Within this group the percentage of elevated (greater than or equal to 4.0 ng/ml) assays increased with UICC clinical stage and was 14.8% (12/81), 23.7% (27/114), 73.1% (190/260) and 20.0% (49/245) for stages I, II, III, IV and X (unstagable due to insufficient data) patients. We have now followed the above 482 stages I, II, III and X patients in whom CEA was performed less than or equal to 3 months after initial surgery at a time when there was no evidence of residual disease, for an average interval of 255 days from date of diagnosis. At present 16.2% (17/105) of patients with elevated CEA values compared to only 4.8% (18/377) of patients with normal values have developed recurrent disease (p less than .0005). There is an association of elevation of CEA postoperatively with different clinical stages of breast cancer. Elevated CEA levels postoperatively are associated with an increased risk of development of recurrent disease in breast cancer patients.

Breast Neoplasms↗

Is there any association between the pharmacologic control of prolactin release and its action on mammary carcinogenesis in the rat?

Pretreatment of female Wistar rats with various compounds (coumarin, 4-methyl-phenobarbital, carbon tetrachloride) on mammary tumour production by 7,12-dimethylbenz(a)anthracene (DMBA) has been studied. The test compounds brought about a variety of actions on DMBA tumours; their effect varied from none (phenobarbital, carbon tetrachloride) to decreased incidence and delayed appearance (coumarin, 4-methylcoumarin). In all cases studied increased prolactin level was found. The inhibitory action of coumarin on tumour incidence and multiplicity showed a dose-related association with elevated serum prolactin and reduced hepatic drug metabolism. These results indicate that the production of DMBA-induced mammary adenocarcinomas in the rat is not associated with serum levels of prolactin. Our results suggest that in this model for tumorigenesis, prolactin only plays the role of a promoter after the carcinogenic event.

9,10-Dimethyl-1,2-benzanthracene↗

Patterns of in vivo lymphoid responses to tumour specific antigens.

A tumour-derived antigen complex injected induced a different cellular immune response in tumour-bearing mice when compared with unprimed controls. A different statistical approach, namely the linear correlation, allowed us to discern significant differences in the response pattern.

Animals↗

Cerebellar dysgenesis in rats by diaplacental effects of 7,12-dimethylbenz[a]anthracene.

7,12-Dimethylbenz[a]anthracene (DMBA) administered iv to pregnant Sparague-Dawley rats produced cerebellar malfunction in at least 10% of the offspring. The underlying morphologic basis of the cerebellar symptomatology was found in maldevelopment of cerebellar cortex, ranging from focal loss of granule and Purkinje's cell layers to extensive areas of cortical disorganization with losses of granule neurons. An interference with the proliferation of the granule cell-layer primordium was suggested as a mechanism of this cerebellar dysgenesis. After a 200-day observation, no tumors were found in the offspring of the DMBA-treated, pregnant rats.

9,10-Dimethyl-1,2-benzanthracene↗