A brain-tumor model utilizing stereotactic implantation of a permanent cannula.

A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups.

Attempts to increase intratumoral blood flow in the rat solid Walker 256 tumor by the use of the perfluorocarbon emulsion fluosol-DA.

We have examined the effect of the perfluorocarbon emulsion, Fluosol-DA 20% (FDA), on blood flow in rats bearing an advanced solid Walker 256 tumor implanted s.c. Blood-FDA exchange in unanesthetized rats maintained under 100% oxygen was accomplished by simultaneous arterial withdrawal and i.

Increases in brain tumor and cerebral blood flow by blood-perfluorochemical emulsion (Fluosol-DA) exchange.

It has been suggested that oxygen-carrying blood substitutes, perfluorochemical (PFC) emulsions, can increase blood flow and oxygen delivery to poorly perfused tumor regions. Local cerebral blood flow was measured in male Wistar rats bearing intracranial Walker 256 tumor with and without blood-PFC exchange using [14C]iodoantipyrine (IAP) and quantitative autoradiographic techniques. The exchange transfusion was performed in two groups of awake animals breathing 100% oxygen: (a) complete blood-PFC exchange, hematocrit 4%; and (b) partial blood-PFC exchange, hematocrit 20-25%.

Dissociation of 5-fluorouracil-induced DNA fragmentation from either its incorporation into DNA or its cytotoxicity in murine T-lymphoma (S-49) cells.

We have shown previously (W. B. Parker and P.

Comparison of the bioavailability of uridine in mice after either oral or parenteral administration.

We compared the bioavailability of uridine (Urd) (350 and 3500 mg/kg) administered either as a single SC injection or by gavage, in male CD8F1 mice. Plasma samples were analyzed for Urd and uracil (Ura) using high-pressure liquid chromatography. After Urd (3500 mg/kg, SC), plasma Urd levels peaked at 4900 microM and then declined to pretreatment levels (less than 10 microM) within 6 h.

Enhancement by uridine of the anabolism of 5-fluorouracil in mouse T-lymphoma (S-49) cells.

Uridine enhances the growth inhibition due to 5-fluorouracil (FUra) in a cultured mouse T-cell lymphoma (S-49). Using colony formation assays we found that cytotoxicity produced by 24-h continuous exposure to FUra (0.5 to 3.

Use of uridine rescue to enhance the antitumor selectivity of 5-fluorouracil.

We examined the ability of uridine to increase the therapeutic index of 5-fluorouracil (FUra) against C57BL/6 X DBA/2 F1 mice bearing a Day 1 B16 melanoma or L1210 leukemia. FUra (400, 600, or 800 mg/kg, i.p.

Uridine rescue from the lethal toxicity of 5-fluorouracil in mice.

To determine the relationship between 5-fluorouracil (FUra) toxicity and its RNA- and DNA-directed actions we examined the ability of continuous SC infusions with uridine (Urd), thymidine (dThd), or deoxyuridine (dUrd) to rescue mice from the lethal toxicity of FUra. Male B6D2F1 mice were treated with a single IP injection of FUra (800 mg/kg) followed in 24 h by a 5-day infusion with either 0.9% NaCl or Urd (0.

Biochemical and pharmacologic study of therapeutic synergism with cyclophosphamide plus methotrexate in murine L1210 leukemia.

The combination of cyclosphosphamide (CP) plus methotrexate (MTX) was found to be therapeutically synergistic against the L1210 ascites tumor. After inoculation with 1 x 10(6) L1210 cells to (C57BL/6 x DBA/2)F1 mice, ip administration of CP (200 mg/kg on Day 5) plus MTX (15 mg/kg on Days 5, 7, 9, and 11) resulted in a significant increase in mean lifespan, compared to optimal treatment with either CP or MTX alone. The contribution of the single, simultaneous dose of CP plus MTX on Day 5 to therapeutic synergism was examined.

Effect of concurrent calcium leucovorin infusion on 5-fluorouracil cytotoxicity against murine L1210 leukemia.

We examined the effect of concurrent SC infusion of calcium leucovorin (LV) on the action of 5-fluorouracil (FUra) against mouse L1210 leukemia implanted either SC or IP. Mice bearing the SC tumor treated with FUra (100 mg/kg, IP, day 1) plus infusion with either LV (11.5 mg .

Studies of the effects of treatment with 5-flourouracil alone and in combination with either cyclophosphamide, methotrexate, or methyl-CCNU on hepatic drug-metabolizing enzymes in murine L1210 leukemia.

Studies have been conducted on liver microsomal enzymes of B6D2F(1) mice bearing a Day 4 L1210 ascites tumor after treatment with a single intraperitoneal injection of 5-fluorouracil (FUra) alone, and in combination with either cyclophosphamide (CP), methotrexate (MTX), or methyl-CCNU (MeCCNU). FUra (200 mg/kg) alone did not alter either ethylomorphine N-demethylase, aniline hydroxylase, or neotetrazolium reductase activities as compared to untreated nontumor-bearing mice on Days 2, 4 and 6 after treatment. FUra (50 mg/kg)d plus CP (200 mg/kg) decreased neotetrazolium reductase activity 17% on Days 4 and 6 after treatment and the enzyme activity then returned to control levels on Day 8.

Effects of 5-fluorouracil on human colon carcinoma and solid rat Walker 256 carcinosarcoma: evaluation as in vitro predictors of clinical response.

Several biochemical effects of 5-fluorouracil (5-FU) including inhibition of the incorporation of 3H-deoxyuridine (3H-UdR) into DNA, inhibition of ribosome formation, and formation of 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) were examined in samples of human colon carcinomas to determine if any of these drug effects might have predictive value as a reliable guide to 5-FU therapy. For comparison, the solid rat Walker 256 carcinosarcoma, which is only minimally responsive to 5-FU, was also studied. For each of the biochemical effects of 5-FU measured in the various samples of Walker 256 tumors, the responses were consistent and varied within a narrow range.

Distribution of anticancer agents in spontaneous animal tumors. II. Distribution of gallium in canine lymphosarcoma.

The physiologic disposition of pharmacologic doses of gallium was studied in control dogs and dogs with spontaneous lymphosarcoma. Gallium 67 (67Ga) was administered iv with carrier gallium added at a dose of 8 mg/kg. About 50% of the injected dose was excreted in the urine by 48 hours (mostly in the first 12 hr), whereas negligible amounts were excreted in bile.

The kinetics of methotrexate distribution in spontaneous canine lymphosarcoma.

A mathematical model is presented to simulate the time-dependent uptake of methotrexate in spontaneous canine lymphosarcomas in vivo. Blood flow ratew in these tumors are high so that transport to the tumor is limited by cell membrane resistance. A significant amount of rapidly exchangeable methotrexate appears to exist in extracellular space loosely bound to proteins or cell membranes.