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PubMed1985

Studies on 18F-labeled pyrimidines III. Biochemical investigation of 18F-labeled pyrimidines and comparison with 3H-deoxythymidine in tumor-bearing rats and mice.

Metabolic studies of 18F-labeled 5-fluoro-2'-deoxyuridine(FdUrd), 5-fluorouridine(FUrd) and 5-fluorouracil (FUra) were performed in tumor-bearing rats and mice. Also, the usefulness of 18F-FdUrd and 3H-deoxythymidine (dThd) for tumor detection was compared. In the tumor, 2 h after the injection of the 18F-pyrimidines, 3%-11% and 6%-14% of the 18F was present in the nuclear and microsomal fractions, respectively, and 17%-34% and 19%-24% of the 18F was incorporated into the acid-insoluble and nucleotide fractions, respectively. Of the three 18F-pyrimidines, 18F-FUrd demonstrated the highest incorporation rate, while 18F-FUra showed the lowest incorporation rate. The incorporation in the spleen, small intestine, and liver was less than that in the tumor. 3H-dThd and 18F-FdUrd were injected into the same mice. The 3H-dThd was accumulated in the spleen, small intestine, and tumor, and in these three tissues significant amounts of the 3H were incorporated into acid-insoluble materials. However, the clearance of 18F-FdUrd was slow in the tumor but rapid in the spleen and small intestine. In the autoradiograms of the tumor, 18F and 3H showed a slightly different distribution. Both distribution patterns were unchanged when the soluble materials were rinsed out with perchloric acid. For tumor detection, 18F-FdUrd gives the same information as radio-dThd, and further information can be obtained by positron-emission tomography.

Animals↗
PubMed1987

Prevention of experimental liver metastases by D-galactose.

The metastasis of malignant tumors from a primary site to near and distant secondary sites is probably the most important event in the pathogenesis of cancer and it accounts for most cancer deaths. Whereas advances in the treatment of primary cancer have led to increased patient survival, metastatic cancers are still the most difficult group of diseases to treat successfully. As organ-characteristic lectins play an important role in the organ manifestation of metastatic islets, it might be possible (e.g. during surgical operations on malignant tumors) to block those organ-characteristic lectins with the appropriate receptor-bearing glycoconjugates in order to inhibit the metastatic spread. Recent experiments have demonstrated that neuraminidase treatment of tumor cells (mouse sarcoma-1) alters in vivo (Balb/c-mice) the organotropic distribution of metastases; instead of being found exclusively in the lung, they are found both in lung and liver. However, pre-injection and regular application of D-galactose--the same holds for arabinogalactan--prevents the setting of metastases in the liver but does not influence the metastatic process to the lung, whereas mannan--as a galactose-free control substance--does not alter the initial pattern of metastasis to lung and liver.

Animals↗
PubMed1983

Induction of 2',5' oligo(A) synthetase in tumor-bearing mice with encephalomyocarditis (EMC) virus or poly(I)poly(C).

Infection of 13 month-old C3H mice with EMC virus or inoculation with the interferon inducer poly(I)poly(C) results in elevated levels of the enzyme 2',5' oligo(A) synthetase only in animals with spontaneous tumors (breast cancer or hepatomas). High enzymatic activities are detected in homogenates from liver, spleen, plasma and neoplastic cells of the animals with breast carcinomas and only in the neoplastic liver cells of the animals with hepatomas.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Effect of ovariectomy, hypophysectomy and/or GnRH analog (HRF) administration on the cell proliferation of the MXT mouse hormone-dependent mammary tumor.

The MXT tumor is an experimental mammary neoplasm which is maintained by serial transplantation using B6D2F1 mice, and which contains significant amounts of estrogen and progesterone receptors. The aim of the present study is to examine the effects of ovariectomy (OVX) or ovariectomy plus hypophysectomy (OVX-HX) on both the macroscopic growth and the cell proliferation of this tumor. This cell proliferation was evaluated by means of in vivo tritiated thymidine autoradiography. In addition, we investigated the effects of a GnRH analog (Gonadorelin: HRF, 5-oxo-Pro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-hydrochloride) on MTX tumor cell proliferation on 7 day-OVX and 5 day-HX (OVX-HX) mice. The uterine luminal epithelium was chosen to monitor the methodology. Our data clearly demonstrate that there is a delay in the growth of MXT tumors grafted into hypophysectomized animals and, to a lesser degree, ovariectomized animals. With respect to proliferation, castration induced a dramatic decrease of the thymidine labelling index (TLI) in the tissue used to monitor the methodology (the uterine luminal epithemium); in contrast, no cell proliferation was induced by hypophysectomy or HRF administration. In 4-week-old MXT tumors, ovariectomy also markedly decreased the TLI within a few days of its taking place. However hypophysectomy, performed on castrated animals, induced a significant and transient increase of cell proliferation in this neoplasm, an increase which lasted from the 2nd to the 5th day following the operation. The high basal level of MXT cell proliferation recorded in OVX-HX animals decreased dramatically after the administration of HRF between 12 and 48 h prior to the sacrifice of the animals. It is concluded that the HRF exerts a direct effect on the MXT tumor cells, and this HRF might be essential for their growth.

Animals↗
PubMed1981

Tumor shedding and coagulation.

Three syngeneic carcinomas from two species shed plasma membrane vesicles when cultured in vitro or grown in the ascites tumor form in vivo. Shed vesicles carry procoagulant activity that can account for the activation of the clotting system and the fibrin deposition associated with these and many other types of malignancy in animals and man.

Animals↗
PubMed1979

Impaired maturation of mouse mammary tumor virus precursor polypeptides in lymphoid leukemia cells, producing intracytoplasmic A particles and no extracellular B-type virions.

Processing of polypeptides of the mouse mammary tumor virus, a type B retrovirus, was investigated in a transplanted thymic lymphoma cell line of the GR strain (GRSL). This cell line was maintained in vivo in ascites form and in vitro as a suspension culture. GRSL cells produce clusters of intracytoplasmic A particles and are virtually deficient in the production of mature extracellular B-type particles. As control, a mammary tumor cell line of the same mouse strain capable of complete virion synthesis was used. The kinetics of viral polypeptide synthesis were studied by pulse labeling with various isotopes (including (35)S and (32)P), followed by immunoprecipitation of cell lysates with monospecific antisera to the major mouse mammary tumor virus gag and env proteins, p27 and gp52, respectively. Both the primary gag and env precursor polypeptides were synthesized in the GRSL cells, but their conversion into viral proteins was impaired. The major gag precursor, Pr73(gag), was stable over a period of 8 h, and mature viral core polypeptides could not be detected. Also, the highly phosphorylated intermediates in the proteolytic processing of Pr73(gag) in virus-producing cells were absent in GRSL cells. By immunoprecipitation, Pr73(gag) was detected in a GRSL particle fraction with the density of intracytoplasmic A particles. The precursor for envelope proteins, Pr73(env), was turned over without the generation of mature viral envelope components gp52 and gp36. The in vivo-transplanted ascites GRSL cells, however, were shown to express gp52 on the cell surface together with a 73,000-dalton polypeptide, as indicated by cell surface iodination and immunoprecipitation.

Animals↗
PubMed1986

[The effect of an arginine-imbalanced diet on the growth of implanted MM-48 and MH-134 tumors in C3H/He mice].

The arginine-imbalanced diet used in this study was a diet of 27% casein supplemented with 8% arginine monochloride. There was no difference in the serum protein level between C3H/He mice fed a casein diet (N-mice) and mice fed on the arginine-supplemented diet (A-mice). The serum arginine level was increased in the A-mice compared with the N-mice. Significant inhibition of MM-48 tumor incidence was seen in the A-mice when the transplanted tumor was below 5 X 10(6) cells. Growth inhibitory effect against MM-48 tumor was significantly enhanced in the A-mice with i.p. injection of OK-432. Interferon production of spleen cells was increased in the A-mice compared with the N-mice. We speculate that the effect of arginine depends partially on the immune functions in the mice.

Amino Acids↗
PubMed1986

Antitumor effect of human necrosis factor on human hepatoma cells PLC/PRF/5.

The antitumor activity of natural human tumor necrosis factor (TNF) on a human hepatoma cell line PLC/PRF/5 was studied in vitro. TNF produced by the LuKII human lymphoblastoid cell line showed a cytostatic effect on the hepatoma cells, whereas the growth of non-tumorigenic Chang liver cells was little affected. The combined effects of TNF and interferon-gamma (IFN-gamma) were additive on the PLC/PRF/5 cells as shown by statistical analyses. The same combination showed synergistic effects on a human breast cancer cell line BT-20, which was highly sensitive to TNF. These data may provide some informations concerning the use of TNF in the treatment of hepatoma.

Animals↗