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C C Stock

Publications and source records attributed to C C Stock.

At least 19 recordsLinked to original sources

Prevention of leukemia and the increase of plasma levels of lipid-bound sialic acid by allogeneic bone marrow transplantation in mice.

AKR/J (hereafter called AK) mice treated by total-body irradiation plus syngeneic marrow transplantation developed a leukemia-lymphoma complex and concomitantly showed increased levels of lipid-bound sialic acid as was also seen in untreated AK mice between 6 weeks and 6 and 11.5 months of age. C57BL/6J (hereafter called B6) mice did not show a leukemia-lymphoma complex and did not develop elevated levels of lipid-bound sialic acid with aging. B6----AK chimeras, prepared with B6 bone marrow deprived of Thy-1,2-positive cells prior to allogeneic transplantation and kept in laminar flow isolation, did not develop graft-versus-host reactions, lived long lives (observations carried up to 13 months), failed to develop leukemia-lymphoma, and had persistently low levels of lipid-bound sialic acid. These findings indicate that introduction of resistance by marrow transplantation can inhibit development of retrovirus-induced cancer and also prevents an increase in levels of a putative cancer indicator.

Animals

Serum lipid-bound sialic acid as a marker in breast cancer.

The reliability of lipid-bound sialic acid (LSA) as a marker in breast cancer was evaluated in 78 normal subjects, 106 patients with benign breast disease, 64 patients with primary operable breast cancer, and 61 patients with recurrent metastatic breast cancer. LSA levels were determined before and after mastectomy and during chemotherapy in selected patients to determine the value of LSA in monitoring therapy and predicting response. LSA levels greater than 20 mg/dl were not seen in normal subjects but were present in patients with benign breast disease (13%), primary breast cancer (47%) and recurrent metastatic breast cancer (62%). LSA levels decreased after initiation of chemotherapy and remained low in patients clinically disease-free. Recurrences were associated with elevated LSA in patients failing chemotherapy or endocrine ablative surgery. LSA measurements appeared to be of limited value in the detection of breast cancer but serial measurements may be useful in assessing disease progression and identifying patients resistant to therapy.

Adult

Effects of selected compounds on the McCall rat colon adenocarcinoma.

Forty-seven substances were tested for antitumor activity against the McCall rat colon adenocarcinoma. The most effective compounds were mitomycin C, 1,1', 1"-phosphinothiolylidynetrisaziridine and adriamycin. Others less active were azaserine, N-(4-chlorophenyl)-N'-(1-methylethyl)-imidodicarbonimidic diamide and 3,6-bis(5-chloro-2-piperidinyl)-2,5-piperazinedione. A number of standard anticancer drugs, 5-fluorouracil, arabinosylcytosine, methotrexate, bleomycin, daunomycin, 6-mercaptopurine, cis-dichlorodiammine platinum(II), cyclophosphamide and actinomycin D, were not effective under the test conditions and evaluation procedure used. Lentinan, though causing no initial inhibition of growth, did cause some regression. Significant synergism in terms of regression was seen in combination therapy with mitomycin C and azaserine.

Adenocarcinoma

Therapy of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas with combinations of 5-fluorouracil and 2 alpha-methyldihydrotestosterone propionate.

This investigation was undertaken to determine whether a combination of a cytotoxic drug with a sex hormone would provide efficacious therapy for mammary carcinomas. Established, 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas were treated with 5-fluorouracil (5-FUra) and 2 alpha-methyldihydrotestosterone propionate (MDTP) for 4 weeks. At end of therapy, pooled data showed 21% of the tumors in complete remission (CR) in rats given 5-FUra at 17.5 mg/kg/day and 3% in those given 8 mg/kg/day. Administration of MDTP at 1.25 to 5 mg/kg/day yielded 15 to 48% tumor CR. The combination of 5-FUra at 17.5 mg/kg/day with MDTP at 5, 2.5, and 1.25 mg/kg/day induced, respectively, 96, 91, and 75% CR. Maxima of 100, 100, and 92% CR were obtained in single tests at these respective doses. Therapy with combinations of 5-FUra at 8 mg/day and MDTP at 2.5 and 1.25 mg/kg/day yielded, respectively, 69 and 61% tumor CR. Appearance of new tumors during and after therapy was controlled more effectively by combinations of the two agents. Analysis of percentage of tumor CR showed marked synergism for 5-FUra and MDTP. A second course of combination therapy effectively prolonged duration of CR. Therapy with the cytotoxic drug 5-FUra in combination with the androgen analog MDTP is highly efficacious against induced mammary carcinomas.

9,10-Dimethyl-1,2-benzanthracene

Lipid-associated sialic acid test for the detection of human cancer.

A rapid method for the measurement of serum and/or plasma, lipid-associated sialic acid levels has been developed. This test has been applied to 850 human sera of which 670 came from patients with nine categories of malignant disease, 80 from persons with benign disorders, and 100 from normal individuals. Lipid-associated sialic acid concentrations were found to be significantly increased (p less than 0.001) in all groups of cancer patients as compared to both those with benign diseases and normal controls. Test sensitivity in the detection of cancer ranged from 77 to 97%. Specificity was, respectively, 81 and 93% for the benign and normal groups. In small samples of patients, no association between test values and tumor burden was found. This test compares favorably with the most widely used tumor marker test, that for carcinoembryonic antigen.

Breast Neoplasms

Ganglioside profiles of metastases and of metastasizing and nonmetastasizing rat primary mammary carcinomas.

The possible relationship between ganglioside levels and ganglioside profiles in malignant tumors and the formation of metastasis was investigated by the analysis of gangliosides in metastasizing SMT-2A and nonmetastasizing MT-W9a mammary carcinomas as well as in metastases formed from SMT-2A tumors. The extracted lipid of SMT-2A tumors contained 3.3-fold more lipid-bound sialic acid than did that of MT-W9a tumors. THe differences were also substantial in the ganglioside profiles in these 2 tumors. Plasma membranes isolated from SMT-2A tumors also contained 1.8-fold more lipid-bound sialic acid than did plasma membranes from MT-W9a tumors. Ganglioside profiles in two types of SMT-2A secondary tumors were investigated. The lipid-bound sialic acid content was 1.5-fold higher in tumor nodules in the lung and 1.9-fold higher in axillary lymph node tumors than it was in primary SMT-2A tumors. The ganglioside pattern in these 2 secondary tumors generally reflected that found in SMT-2A: high levels of gangliosides containing three or four sialic acid molecules. The lung nodule retained its specificity with respect to lipid-bound sialic acid content and ganglioside pattern after the lung nodule was sequentially transplanted three times to the site of the original SMT-2A tumor growth.

Animals

Plasma lipid bound sialic acid in patients with prostate and bladder cancer.

Plasma lipid bound sialic acid (LSA) was measured in patients with prostate and bladder cancer to determine the usefulness of this biochemical marker in teh staging of malignant disease and in monitoring the efficacy of therapy. Patients with advanced stages of prostate cancer with bone metastases exhibited LSA levels significantly higher than normal subjects. Patients with bladder cancer showed elevations in LSA both in early noninvasive and in advanced stages of the disease. In both types of cancer, patients treated successfully and clinically free of disease did not have elevated LSA levels, whereas patients failing to respond to treatment had persistently high values.

Adult

Possible relationship between glycosphingolipids and the formation of metastasis in certain human experimental tumors.

Two tumors, human sarcoma #1 (HS #1) and human epidermoid carcinoma #3 (HEp #3), were cultured on the chorioallantoic membrane of chick embryos. Under experimental conditions, HS #1 does not metastasize, whereas HEp #3 metastasizes extensively to chick embryo lungs and other organs. The glycosphingolipid profiles of these tumors were studied and HEp #3 wad found to contain about 2.5-fold less lipid-bound sialic acid per 100 mg of total lipid extracted than did HS #1, due mainly to smaller levels of monosialoganglioside (3.7-fold) and disialoganglioside (3.8-fold) in HEp #3. The total amount of neutral glycosphingolipids was approximately the same in both tumors, but their profiles differed. Treatment of these tumors with 6,7,8,9-tetrahydro-1-mercapto-1,2,4-triazolo-[4,3-a]quinazolin-5-ol (2.5 mg/egg/tumor) completely inhibited the formation of metastases in HEp #3 and increased the total content of lipid-bound sialic acid in the tumor by 63% (hematoside, monosialoganglioside, and disialoganglioside by 71, 99, and 67%, respectively). No change was seen in the content of lipid-bound sialic acid in HS #1. Treatment of HEp #3 with a smaller dose of te quinazolinol derivative (1.25 mg/egg) caused an average of 88% inhibition of metastasis, with a 37% increase in lipid-bound sialic acid. Another compound, 2,5-diphenylthiazolo-[5,4-d]thiazole (500 microgram/egg), completely inhibited the formation of metastasis and caused a substantial increase in the amount of lipid-bound sialic acid (77%). The data showed the existence of a correlation between the level of gangliosides in HEp #3 and the ability of these tumors to metastasize.

Animals

Glycosphingolipids of subcellular fractions from normal rat liver and Morris hepatoma 5123TC.

Neutral glycosphingolipids and gangliosides were quantified in lipid extracts from plasma membranes, mitochondria, microsomes, and nuclei isolated from normal rat liver and Morris hepatoma 5123TC. Results showed a higher content of glycosphingolipids, especially gangliosides, in hepatomas and differences in the distribution of glycosphingolipids among subcellular fractions. Differences in the glycosphingolipid composition of the hepatoma, namely, the absence of trisialogangliosides and an increase in the lower molecular weight gangliosides, reflected an altered metabolism of glycosphingolipids in this tumor. The results indicated that changes in membrane glycosphingolipids were not restricted to the cell surfaces of malignant cells, inasmuch as intracellular membrane fractions also exhibited altered glycosphingolipid profiles.

Animals

Sensitivity to chemotherapeutic and immunomodulating agents of two mouse lymphomas and of a macrophage tumor.

The effect of treatment with 15 chemotherapeutic and 10 immunomodulating agents on the growth of T-cell lymphoma EL-4, macrophage tumor J774, and B-cell lymphoma 70Z/2 of the mouse has been studied using the prolongation of median survival time of tumor-bearing hosts as an index of therapeutic effectiveness. The survival time of mice bearing 70Z/2 was prolonged more than 100% by single-agent therapy with actinomycin D, cyclophosphamide, 6-mercaptopurine, mitomycin C, and vinblastine; a similar response of J774 was produced by therapy with Adriamycin, cyclophosphamide, or 6-mercaptopurine. No chemotherapeutic agent prolonged the median survival time of mice bearing EL-4 by 100% or more. Of the immunomodulating agents, mycobacterial preparations (Bacillus Calmette-Guérin or interphase material), Corynebacterium parvum, and polyinosinic-polycytidylic acid moderately prolonged the survival time of mice bearing J774 or 70Z/2; the EL-4 lymphoma was refractory to all 10 immunomodulating agents.

Adrenal Cortex Hormones

Discrete separation of HDL2 from HDL3 of human serum by means of polyacrylamide gel.

A relatively short, simple procedure is presented to separate serum high-density lipoproteins discretely into the two main classes, those with densities between 1.063 and 1.125 g/ml (HDL2) and those with densities between 1.125 and 1.210 g/ml (HDL3). A 3.5% polyacrylamide gel in 10 cm glass tubes and the use of Tris/glycine buffer, pH 8.4, will accomplish this separation. The components can be identified in several different ways, examples of which are given. This procedure will give rapid and reliable estimations of both HDL2 and HDL3, and can be used to relate their levels and proportional amounts to incidence or risk of atherosclerosis, coronary-artery disease and possibly cancer.

Adult

Antitumor tests of amygdalin in transplantable animal tumor systems.

Except for oral administration, there was no grossly observed toxicity from carefully administered high doses of amygdalin in the experimental systems used. The compound in high doses was ineffective against the DMBA-induced rat mammary carcinoma and the following transplanted experimental tumors: Sarcoma 180, plasma cell tumor LPC-1, leukemia L1210, Mecca lymphosarcoma, Ridgway osteogenic sarcoma, sarcoma T241, mammary carcinoma E0771, Taper liver tumor, Ehrlich carcinoma (solid and ascites), and Walker carcinosarcoma 256. Amygdalin did not noticeably influence the toxicity or impair the efficacy of these chemotherapeutic agents in their respective systems: Cytosine arabinoside, methotrexate, cytoxan, or 5-fluorouracil in L1210; the latter two in LPC-1; 6-mercaptopurine in Ridgway osteogenic sarcoma; estradiol-17beta or 2alpha-methyldihydrotestosterone propionate in the DMBA-induced rat mammary carcinoma.

Amygdalin

Antitumor tests of amygdalin in spontaneous animal tumor systems.

In a series of 6 experiments with CD8F1 mice with spontaneous mammary adenocarcinomas Sugiura noted by macrovisual observation with some histology an overall average of 21% of mice with lung metastases when treated with 1,000--2,000 mg/kg/day of amygdalin compared with 90% of the control mice. The significance attributed to those early observations is seriously challenged by the negative findings of 3 independent investigators, by 2 out of 3 negative cooperative experiments in which Sugiura participated, and particularly by the blind experiment in which he and others under blind readings found no anticancer activity. Treatment of Swiss albino mice showed no destructive effect upon their spontaneous mammary adenocarcinomas. Of the treated mice, 22% were found by macrovisual observation to have lung metastases while 91% were noted among the controls. The results are subject to questions raised in the discussion. Amygdalin at 2,000 mg/kg/day was ineffective both in treating and preventing the development of spontaneous leukemia in AKR mice. At 1,000 mg/kg/day it was not found effective in preventing or significantly delaying the development of spontaneous mammary tumors in CD8F1 mice. In summary, we do not have evidence to support taking amygdalin to clinical trial, although other considerations may require that one be conducted.

Adenocarcinoma