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Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function.

Plasma immunoreactive alpha-human atrial natriuretic polypeptide (Ir-alpha-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-alpha-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 +/- 79.6 versus 28.7 +/- 12.2 pg/ml, P less than 0.001). In cirrhotics without ascites, Ir-alpha-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that alpha-hANP was closely related to renal circulation and sodium homeostasis. On the contrary, in cirrhotics with ascites Ir-alpha-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-alpha-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-alpha-hANP levels. On the basis of the Ir-alpha-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-alpha-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-alpha-hANP changes in the 2 groups.

Adult↗

Non-bicarbonate buffering of ascites tumor cells in the rat as titrated by strong acids.

Buffer equations originally derived for blood were applied to the in vitro system "ascites tumor cells and ascitic fluid'. Non-bicarbonate buffer values beta(mmol x pH(-1) x 1(-1)) were determined experimentally by titration of ascites, cell free ascitic fluid and cell homogenates with NaOH in the absence of CO2. beta in ascitic fluid, in native ascites and in cell homogenate were beta (F) = 5.9, beta (A) = 16.4 and beta (H) = 24.9, respectively. Intracellular beta value beta (C) calculated from buffer equations depended on the ratio delta pHi/delta pHe. With delta pHi/delta pHe = 1, beta (C) was 38.8. The difference between beta (C) and beta (H) could be partly accounted for by differences in the cellular protein content. With delta pHi/delta pHe = 0.62 as in the presence of CO2, beta (C) becomes 62.6. In the presence of CO2 (see Albers et al., 1981), the extracellular buffering was higher and the intracellular buffering lower than the values titrated in the absence of CO2. It is concluded that in the presence of CO2 and/or HCO3- the apparent intracellular buffering of intact tumor cells results from non-bicarbonate buffering by cell proteins as well as from active or passive ionic exchanges with the extracellular fluid.

Acid-Base Equilibrium↗

The effect of the mode of administration of nitrogen mustard and cytosine arabinoside on the production of chromosomal aberrations in mouse bone marrow and ascites tumour cells.

The cytogenetic effects of intraperitoneally (i.p.) and subcutaneously (s.c.) administered nitrogen mustard (HN2) and cytosine arabinoside (ara-C) on bone-marrow and ascites tumour cells of mice were studied. Ehrlich ascites tumour-bearing mice were treated with the mutagens, and cytological preparations were made from ascites tumour and bone-marrow cells of the same animal. The following parameters were investigated: frequencies of mitotic and chromosomal aberrations, time of aberration maxima and aberration spectra. HN2 (0.68 mg/kg b.w.), when given i.p., induced in ascites tumour cells a strong inhibition of mitotic frequency and very high aberration rates, whereas in bone marrow no aberrant chromosomes were observed. On the other hand, after s.c. administration, the same dose induced more aberrant metaphases in bone marrow than in tumour cells. Ara-C (315 mg/kg b.w.) resulted, after s.c. administration, in higher aberration frequencies both in ascites and bone-marrow cells compared with i.p. treatment. All ascites tumour cells showed higher aberration requencies than bone-marrow cells. In bone marrow the aberration maximum occurred as soon as 6 h after treatment. Furthermore, clear differences with respect ot the types of aberration found in the two systems were evident. The differences caused by the different modes of administration in two different types of cell are discussed in terms of metabolic inactivation and differences of the two tissues with respect to karyotype, cell cycle time and repair capacity.

Animals↗

Proapoptotic and antitumor activities of the HMG-CoA reductase inhibitor, lovastatin, against Dalton's lymphoma ascites tumor in mice.

BACKGROUND: Diet rich in fat have a clear effect on the tumor incidence in humans. Increased level of lipid peroxidation were found in colon, liver, breast and kidney carcinogenesis. Although the beneficial effects of statins for cardiovascular diseases are well established, their importance in the area of cancer therapeutics has recently gained recognition. Many studies of lovastatin in in vitro systems and experimental animals have been reported as an effective antitumor agent. However, phase I/II clinical trials in cancer patients demonstrated a minor to non-significant responses. Hence more studies in different tumor models using doses corresponding to that used to reduce lipid in human are required to support the antitumor activity. METHODS: The antitumor activity was evaluated using Daltons' Lymphoma Ascites (DLA) cell line-induced ascites tumor model in mice. Proapoptotic activity was evaluated in DLA cell line induced ascites animals after the treatment of lovastatin. Apoptosis was analyzed morphologically by staining with Giemsa and biochemically by observing the laddering of DNA in agarose gel electrophoresis. In vitro cytotoxic activity of lovastatin was studied by trypan blue dye exclusion method. Lipid peroxidation inhibiting activity was demonstrated in Fe2+-ascorbate induced rat whole liver homogenate. RESULTS: Lovastatin dose dependently inhibited the ascites tumor growth at 4 and 16 mg/kg body wt (p.o). The percentage increase in life span (%ILS) in the 16 mg/kg treated group was 61.8% (P<0.01). Single dose of lovastatin (16 mg/kg body wt, p.o) was also effective to accelerate the apoptosis in the ascites tumor bearing mice that was evident from the multiple fragmentation of DNA in gel electrophoresis. Further the morphological analysis of DLA cells aspirated from the lovastatin treated animals showed a significant (P<0.01) increase of apoptotic cells (15.5+/-3%) than the control animals (6.5+/-1%). Concentration of lovastatin required for the 50% of the cytotoxicity was 37+/-5 microg/ml. Lovastatin at its low concentrations were effective to inhibit lipid peroxidation. CONCLUSIONS: The antitumor activity of lovastatin against the ascites tumor is due to its proapoptotic and cytotoxic activities. Lovastatin at low concentrations inhibited Fe2+ induced lipid peroxidation in in vitro system. The proapoptotic and lipid peroxidation inhibiting activities of the lipid lowering drug lovastatin may further suggest its possible therapeutic use as a cancer chemopreventive agent.

Animals↗

Abdominal tenderness in ascites patients indicates spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP), which has been reported to be present in 10-30% of patients with cirrhotic ascites, may easily be overlooked. An important aim of our study was to determine whether there are any clinical signs which, in clinical practice, may predict or exclude SBP. METHODS: We studied 133 patients with cirrhotic ascites from medical units at nine Swedish university hospitals where there had been at least one diagnostic ascites tap with analysis of polymorphonuclear leukocytes in the ascites fluid. The patients had initially been questioned about background factors and physically examined according to a standardized case record form. Samples of blood, urine, and ascites were then drawn for analysis according to a structured schedule. RESULTS: SBP could be excluded in 80% of all the cases and was confirmed in 8% of the 133 patients in the final analysis. Abdominal pain and abdominal tenderness were more common in patients with SBP (p<0.01), but no other physical sign or laboratory test could separate SBP cases from the others. CONCLUSIONS: SBP was present in about one-tenth of the hospitalized patients with cirrhotic ascites in this cohort. Performing repeated physical examinations and paying particular attention to abdominal tenderness may be the best way to become aware of the possible development of this complication.

Journal Article↗

Ascitic and solid Ehrlich tumor inhibition by Chenopodium ambrosioides L. treatment.

The leaves of Chenopodium ambrosioides L. [Chenopodiaceae] ('mastruz') have been indicated for the treatment of several diseases, among which the cancer. There are no results focusing the effect of C. ambrosioides treatment on tumor development in vivo. The aim of this study was to investigate the effect of treatment with C. ambrosioides on Ehrlich tumor development. Swiss mice were treated by intraperitoneal route (i.p.) with hydroalcoholic extract from leaves of C. ambrosioides (5 mg/kg) or with PBS (control group) 48 h before or 48 h later the Ehrlich tumor implantation. The tumor cells were implanted on the left footpad (solid tumor) or in the peritoneal cavity (ascitic tumor). To determine the solid tumor growth, footpad was measured each 2 days until the fourteenth day, when the feet were weighed. Ascitic tumor development was evaluated after 8 days of tumor implantation by quantification of the ascitic fluid volume and tumor cell number. The i.p. administration of C. ambrosioides extract before or after the tumor implantation significantly inhibited the solid and ascitic Ehrlich tumor forms. This inhibition was observed in ascitic tumor cell number, in the ascitic volume, in the tumor-bearing foot size and foot weight when compared to control mice. The treatments also increased the survival of tumor-bearing mice. In conclusion, C. ambrosioides has a potent anti-tumoral effect which was evident with a small dose and even when the treatment was given two days after the tumor implantation. This effect is probably related with anti-oxidant properties of C. ambrosioides.

Animals↗

Saphenoperitoneal anastomosis for resistant ascites in patients with cirrhosis.

BACKGROUND: Restriction of salt intake and diuretics combined with repeated paracentesis has been the mainstay of managing longstanding ascites. Peritoneal-venous shunts have been employed in refractory ascites but are not without complication. We evaluated an autologous reversed segment of proximal long saphenous vein anastomosed to the peritoneum in management of patients with resistant ascites. METHODS: Eleven patients (8 male, median age 48 years, range 37 to 68) with tense refractory ascites associated with cirrhosis of the liver and portal hypertension underwent saphenous vein-peritoneal anastomosis by rotating the proximal vein cephalad which was anastomosed to peritoneum in the posterior wall of the inguinal canal. Ten of 11 procedures were performed under general anesthetic. RESULTS: Thirty-day mortality was 1 patient. Morbidity included transient hepatic encephalopathy in 4 (36%), minor wound hemorrhage in 3 (27%), fluid leakage in 7 (64%), and wound infection in 7 (64%). Hospital stay (median) was 16 days (range 11 to 23). In the short term (median of 9 months) significant reduction in body weight and abdominal girth was seen in 9 (90%), 6 (60%) were not on diuretics while 3 (30%) continued to remain on reduced doses of diuretic. Furthermore, 7 (70%) did not require paracentesis. At 2-year follow-up, 5 (45%) patients had died and 3 were lost to follow-up. The remaining 3 were all in active employment, 1 was off diuretics, and 2 were on reduced doses. All 3 patients maintained reduced body weights and abdominal girths compared with preoperative values. CONCLUSIONS: Saphenous-peritoneal anastomosis appears a simple, safe, and effective method of achieving long-term control of refractory ascites. The use of a biological shunt is an added advantage over prosthetic shunts for drainage of ascitic fluid.

Anesthesia, General↗

Biological and structural differences between tRNAVal species isolated from rat ascites hepatoma cells and normal rat liver.

On RPC-5 column chromatography, the main valine acceptor activity of tRNA (tRNA2Val) from rat ascites hepatoma cells was eluted later than that of normal rat liver tRNA (tRNA1Val). The tRNA2Val was aminoacylated by E. coli amino-acyl-tRNA synthetase, while tRNA1Val from normal rat liver was not. Rat fetal liver tRNAVal was also aminoacylated by E. coli aminoacyl-tRNA synthetase. tRNA1Val (rat liver) and tRNA2Val (ascites hepatoma) were each purified to a homogeneous state by RPC-5 column chromatography and two-dimensional polyacrylamide gel electrophoresis, and their sequences were determined by post-labeling techniques. Ascites hepatoma tRNA2Val differed from rat liver tRNA1Val in that Gm18, C32 and an unknown modified nucleoside, N34, in the latter tRNA were mostly replaced by G, Cm, and inosine, respectively. In addition, 3'-terminal adenosine was not present in tRNA1Val (normal rat liver), but was in tRNA2Val (ascites hepatoma). Other modifications and the primary structures of the two tRNAValS were found to be the same. Thus it was concluded that the new iso-acceptor species of tRNA Val in ascites hepatoma cells is due to a change of post-transcriptional modification, not to a change of tRNA transcription. The unique feature of the change of post-transcriptional modification in tRNA2Val (ascites hepatoma) is that both hypo- and hyper-modification take place simultaneously in the tRNA molecule depending the locations of nucleotide residues.

Amino Acids↗

Advantages of treatment of ascites without sodium restriction and without complete removal of excess fluid.

Two modifications of the standard method of treatment of ascites in chronic liver disease were investigated in three separate randomised trials involving a total of 201 patients. These modifications were (1) an unrestricted sodium intake and (2) limitation of diuresis to partial removal of ascites, to the point of relief of abdominal tension. Mean serum sodium fell significantly in all patient groups receiving the low sodium diet and did not fall in the groups given an unrestricted diet. Mean serum urea nitrogen rose significantly in the patient groups undergoing complete diuresis and did not change in the groups undergoing partial diuresis. Mean serum uric acid rose only in the groups undergoing complete diuresis. We concluded that the advantages of these two modifications of therapy of ascites were increased dietary palatability and decreased likelihood of hyponatraemia and of rise in serum urea nitrogen and uric acid. Disadvantages included dissatisfaction of patients over incomplete clearing of ascites, occasional difficulty in performing diagnostic studies because of prolonged ascites, and unsuitability of a high sodium intake in patients whose ascites is highly refractory to treatment.

Blood Urea Nitrogen↗

Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study.

BACKGROUND: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.

Albumins↗

Pseudo-meigs syndrome: uterine leiomyoma with bladder attachment associated with ascites and hydrothorax - a rare case of a rare syndrome.

INTRODUCTION: Pseudo-Meigs syndrome is a rare syndrome with pelvic tumors (not ovarian fibromas), which is combined with ascites and hydrothorax. Up to now 23 cases of pseudo-Meigs syndrome associated with uterine leiomyomas are described. We present a further case of a young woman with pseudo-Meigs syndrome combined with bladder attachment and elevated CA-125. CASE REPORT: A 27- year-old woman complained about increasing abdominal volume for about 2 months. Clinical results showed a normal sized uterus with a pedunculated leiomyoma, ascites, and a small pleural effusion. CA-125 levels were approximately more than 50 times higher than normal range. An explorative laparotomy revealed a leiomyoma and ascites. The myoma was attached to the posterior wall of the bladder; the rest of the uterus and both adnexae were normal. An organ-preserving operation was performed. Three months afterwards the patient presented normal clinical and sonographical findings and normal CA-125 serum levels. DISCUSSION: Uterine leiomyoma is only rarely associated with ascites and hydrothorax. Our case is the 24th in literature. Like other authors we could show elevated CA-125 serum levels. Cases of pseudo-Meigs syndrome with penduculated myomas and tight adhesions of neighbouring structures have been described frequently. In our case the bladder was tightly attached, and the vascularisation seemed to come from the uterus and the bladder. This atypical double supply might be in etiological context with the ascites. Pseudo- Meigs syndrome should be considered as a rare differential diagnosis for ascites and pleural effusions.

Adult↗

Effect of several d-morphinans on ascites tumors in mice.

Dextromethorphan and its analogues (DM 16, DM 34, DM 72, DM 75 and DM 96) were examined for their effect on Ehrlich ascites carcinoma or ascites sarcoma-180 in female mice of the ddY strain. The suspension of Ehrlich carcinoma cells or sarcoma-180 cells was prepared from mice at 10 days after i.p. inoculation of the cells, using Hanks' balanced salt solution, and the cell suspension was inoculated i.p. into mice (2 X 10(6) viable cells/mouse). The chemicals dissolved in physiological saline containing 5% HCO-60 were then injected i.p. into the mice once daily for 5 successive days (5-40 mg/kg/day). In addition, mice given the tumor cells were treated with the saline containing 5% HCO-60 alone for 5 days (untreated mice). In groups of mice bearing Ehrlich ascites carcinoma or ascites sarcoma-180, the mean survival time of mice treated with 20-40 mg/kg/day of DM 96 was more than twice that of the corresponding untreated mice. The mean survival time of mice treated with 20 mg/kg/day of DM 96 was also longer than that of mice treated with 40 mg/kg/day of the other chemicals, irrespective of the ascites tumors. Concerning these survival times, the LD50 (i.p.) of DM 96 in mice differed slightly from that of other chemicals (88 mg/kg and 77-106 mg/kg). These results indicate that DM 96 is more active than the other chemicals against the ascites tumors in mice.

Animals↗

The combination of the tyrosine kinase receptor inhibitor SU6668 with paclitaxel affects ascites formation and tumor spread in ovarian carcinoma xenografts growing orthotopically.

PURPOSE: The purpose of this study was to investigate the antitumor activity of SU6668, tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), fibroblast growth factor receptor 1 (FGFR1), and platelet-derived growth factor receptor beta (PDGFRbeta), as single-agent therapy and in combination with paclitaxel on ovarian carcinoma xenograft models transplanted in the peritoneal cavity of nude mice. EXPERIMENTAL DESIGN: HOC22 and HOC79 ascites-producing human ovarian carcinoma xenografts were transplanted i.p. into nude mice. SU6668 was given p.o. (200 mg/kg, daily) as a single agent or in combination with paclitaxel i.v. (6 mg/kg/dose every other day or 20 mg/kg/dose weekly). Tumor burden was evaluated at the end of the treatment period as ascites volume and tumor cells, VEGF, FGF-2, and PDGF levels in ascites, and involvement of the organ of the peritoneal cavity. Response was evaluated as percentage increment of life span (%ILS). RESULTS: SU6668 affected ascites formation and tumor burden in the peritoneal cavity of nude mice bearing HOC22 and HOC79 xenografts. Decreased levels of VEGF and PDGF in ascites paralleled this effect. The overall survival of the mice bearing HOC xenograft (HOC79 less response than HOC22) was significantly increased by the treatment with SU6668. The magnitude of the effects depended on the length of treatment and tumor burden at the beginning of treatment. The combination of SU6668 with paclitaxel significantly prolonged the survival of mice bearing HOC79, compared with single therapies. SU6668-based combination therapy was more effective with paclitaxel given at the optimal dose and schedule (20 mg/kg every 7 days for 3 doses) than at the same total dose but split (6 mg/kg every 2 days for 10 doses). However, a similar outcome was observed when giving high-dose paclitaxel (20 mg/kg every 7 days for 3 doses) in monotherapy or split low-dose paclitaxel (6 mg/kg every 2 days for 10 doses) but in combination with SU6668. The addition of paclitaxel, by either schedule, to SU6668 treatment inhibited tumor spread in the peritoneal organs (omentum, pancreas, and diaphragm) even at low doses of paclitaxel. A greater effect was observed with prolonged treatments. CONCLUSIONS: This study shows that SU6668 in combination with paclitaxel inhibits ovarian carcinoma progression in the peritoneal cavity, by blocking ascites formation and tumor spread. Because an adequate schedule and dose of the combination might be as effective as conventional chemotherapy, this should be considered as a therapeutic alternative. These findings provide a rationale for the clinical evaluation of combination therapies affecting multiple biological targets in this tumor type.

Animals↗

Effects of dietary fat composition on the Ehrlich ascites tumor fluid lipoproteins.

Mice bearing the Ehrlich ascites tumor were fed diets rich in either coconut oil or sunflower oil. From 20 to 40% less lipid was present in the ascites tumor fluid when the mice were fed the sunflower oil diet. This was associated with a reduction in the amount of very low density lipoproteins (VLDL) and high density lipoproteins (HDL), the main lipoprotein fractions present in the ascites tumor fluid. The VLDL from the mice fed sunflower oil contained more cholesteryl esters and a lower free to esterified cholesterol ratio than those from the mice fed coconut oil. Very little change occurred in the composition of the HDL. All of the lipids contained in both lipoprotein fractions exhibited appreciable differences in fatty acid composition. Much more monoenoic and less polyenoic fatty acid were present in the lipids from the mice fed the coconut oil diet, but no appreciable change in saturated fatty acid content occurred. Similar changes in fatty acid composition were observed in the blood plasma of the tumor-bearing mice. There was no qualitative difference in the apolipoprotein patterns of either the ascites fluid VLDL or HDL. Pyrene fluorescence studies indicated that the fluidity of the VLDL was increased when the mice were fed the sunflower oil diets. No difference in HDL fluidity, however, was observed by this technique. These results indicate that the amount, composition, and physical properties of certain of the lipoproteins contained in the ascites tumor fluid can be modified by changing the composition of the dietary fat fed to mice bearing the Ehrlich ascites tumor.

Animals↗

[Prognostic value of the renin-angiotensin system in response to salt restriction and prognosis of alcoholic ascitic cirrhosis].

Prognostic factors in alcoholic cirrhosis with ascites were analyzed in a prospective study of 37 patients (25 men, 12 women), 26 of whom presented with clinically diagnosed ascites. A good therapeutic response following salt restriction was obtained in 50%; this response correlated well with an initially small ascites volume, male sex, daily urinary sodium excretion of greater than 10 mmol, plasma renin activity of less than 5 ng/ml/hr and a normal plasma aldosterone level. On the other hand, age, number of episodes and duration of ascites, hepatic functional parameters, plasma creatinine concentration and portal venous pressure had no predictive value as to therapeutic response. Patients' survival was inversely related to plasma renin activity and positively to sodium excretion. The one-year mortality rate reached 88% in patients with renin of greater than 5 ng/ml/hr or daily urinary sodium excretion of less than 10 mmol, while 70% of patients with renin of less than 5 ng/ml/hr or daily sodium excretion of greater than 10 mmol survived more than two years. No prognostic index of survival could be derived from age, sex, number of episodes, duration and volume of ascites, portal venous pressure or hepatic biochemical parameters. Thus, in cirrhotic alcoholic patients with ascites the determination of daily urinary sodium excretion, which is inversely related to the activity of the renin-angiotensin system, provides a useful prognostic index for the response to salt restriction and longterm survival.

Adult↗

Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells.

Much of the lipid present in the ascites plasma in which Ehrlich cells grow is contained in very low density lipoproteins (VLDL). Chemical measurements indicated that triglycerides were taken up by the cells during in vitro incubation with ascites VLDL. When tracer amounts of radioactive triolein were incorporated into the ascites VLDL, the percentage uptakes of glyceryl tri[1-(14)C]oleate and triglycerides measured chemically were similar. The cells also took up [2-(3)H]glyceryl trioleate that was added to VLDL, but the percentage of available (3)H recovered in the cell lipids was 30-40% less than that of (1 4)C from glyceryl tri[1-(1 4)C]oleate. This difference was accounted for by water-soluble (3)H that accumulated in the incubation medium, suggesting that extensive hydrolysis accompanied the uptake of VLDL triglycerides. Radioactive fatty acids derived from the VLDL triglycerides were incorporated into cell phospholipids, glycerides, and free fatty acids, and they also were oxidized to CO(2). Triglyceride utilization increased as the VLDL concentration was raised. These results suggest that one function of the ascites plasma VLDL may be to supply fatty acid to the Ehrlich cells and that the availability of fatty acid to this tumor is determined in part by the ascites plasma VLDL concentration. Although Ehrlich cells incorporate almost no free glycerol into triglycerides, considerable amounts of [2-(3)H]glyceryl trioleate radioactivity were recovered in cell triglycerides. This indicates that at least some VLDL triglycerides were taken up intact. The net uptake of VLDL protein and cholesterol was very small relative to the triglyceride uptake, suggesting that intact triglycerides are transferred from the ascites VLDL to the Ehrlich cells and that hydrolysis occurs after the triglyceride is associated with the cells.

Animals↗

Resistance to Ehrlich ascites tumor in a strain of dystrophic mice.

Ehrlich ascites tumor grows in almost any mouse host. We have found a strain of dystrophic mice to be strongly resistant to Ehrlich ascites tumor. Mice of the dystrophic strain survived injection of Ehrlich Ascites tumor cells that had just been passaged through either dystrophic mice or C57BL X DBA/2 F1, (hereafter known as BD2F1) mice. However, most of the dystrophic mice died when they were given injections of Ehrlich ascites tumor cells that had just been passaged through Swiss white mice. All Swiss white and BD2F1 mice died when they were inoculated with Ehrlich ascites tumor cells, regardless of the type of mouse through which the Ehrlich ascites tumor cells had just been passaged. In some dystrophic mice, the tumor grew to a palpabale size and then disappeared. This provided the opportunity to passage the tumor from one dystrophic mouse to another and thereby to demonstrate resistance in the dystrophic mice to tumor that had grown previously in dystrophic mice. There was no detectable difference in the rate of tumor growth in either Swiss white or BD2F1 mice.

Animals↗

Doxorubicin (Adriamycin) transport in Ehrlich ascites tumour cells: comparison with transport in human red blood cells.

The doxorubicin (Adriamycin) transport was investigated in murine Ehrlich ascites tumour cells by measuring the initial rate of cellular net uptake in vitro at 37 degrees C (pH 7.3). Transport characteristics were compared with previously published data on doxorubicin transport in human red blood cells. The apparent permeability coefficient in ascites cells (2.4 X 10(-5) cm sec-1) and in red cells was of the same order of magnitude when calculated from the initial influx into cells suspended in a salt solution (37 degrees C, pH 7.3). Doxorubicin was strongly adsorbed to the cell surface of ascites cells in contrast to the doxorubicin adsorption to red cells when the cells were suspended in a salt solution. The adsorbed doxorubicin could be removed by washing the ascites cells either with DNA or with human albumin salt solutions indicating that the adsorption to cell surface components was reversible. Cell membrane modifiers, 1-alcohols, local anaesthetics, phloretin, HgCl2, para-chloromercuribenzoate, affected doxorubicin transport in ascites tumour cells and red cells in the same manner as these modifiers affected the transport of other lipophilic compounds. Ehrlich ascites tumour cells and human red blood cells appeared to represent two extremes with regard to doxorubicin adsorption to cell surfaces but doxorubicin seems to pass through the rate limiting barrier of the cell membrane by simple diffusion of the uncharged doxorubicin molecule in both cell types.

1-Octanol↗