Effect of complex amino acid imbalance on growth of tumor in tumor-bearing rats.

AIM: To investigate the effect of complex amino acid imbalance on the growth of tumor in tumor-bearing (TB) rats. METHODS: Sprague-Dawley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker-256 carcinosarcoma cells was subcutaneously inoculated. TB rats were randomly divided into groups A, B, C and D according to the formula of amino acids in enteral nutritional solutions, respectively. TB rats received jejunal feedings supplemented with balanced amino acids (group A), methionine-depleted amino acids (group B), valine-depleted amino acids (group C) and methionine- and valine-depleted complex amino acid imbalance (group D) for 10 days. Tumor volume, inhibitory rates of tumor, cell cycle and life span of TB rats were investigated. RESULTS: The G0/G1 ratio of tumor cells in group D (80.5 +/- 9.0)% was higher than that in groups A, B and C which was 67.0 +/- 5.1%, 78.9 +/- 8.5%, 69.2 +/- 6.2%, respectively (P<0.05). The ratio of S/G2M and PI in group D were lower than those in groups A, B and C. The inhibitory rate of tumor in groups B, C and D was 37.2%, 33.3% and 43.9%, respectively (P<0.05). The life span of TB rats in group D was significantly longer than that in groups B, C, and A. CONCLUSION: Methionine/valine-depleted amino acid imbalance can inhibit tumor growth. Complex amino acids of methionine and valine depleted imbalance have stronger inhibitory effects on tumor growth.

Toxicities and therapeutic effect of 5-fluorouracil controlled release implant on tumor-bearing rats.

AIM: To investigate the toxicities, biodistribution and anticancer effect of 5-fluorouracil controlled release implant (5-FUCI) on Walker 256 carcinosarcoma cells in Wistar rats. METHODS: Experiment 1: Wistar rats were randomly divided into three groups (27 rats per group). Blank implant was implanted in left lobe of the liver, and rats were treated with saline solution (in group A) or 5-fluorouracil (subcutaneous injection, group B). 5-FUCI was inserted in left lobe of the liver (group C). The gastrointestinal and hematological toxicities were observed and contents of element F in group C were assayed. Experiment 2: on day 6 after Walker-256 carcinosarcoma transplantation in left lobe of the liver, 5-FUCI was implanted in right lobe of the liver (group E) or left lobe (group F), and rats in control group (group D) were inserted blank implant. Tumor inhibition rate and survival time were investigated. RESULTS: 5-FUCI showed no obvious toxic effect, extraction of Evan's blue from gastrointestinal tissue was normal, the peripheral white blood cells and bone marrow nucleated cells were not reduced, compared with control group (P>0.05). Histological examination revealed that there were no visible changes in small intestinal mucosa, The concentration of 5-fluorouracil in left lobe of the liver was 9.84, 28, 34 times as much as those of right lobe of the liver, heart and kidney respectively after the implantation in group C. They kept a high level of fluorouracil in left lobe of the liver, ranging from (4.414+/-0.482) % to (7.800+/-0.804) %, for eight weeks. Survival days were 28.0+/-2.2, 30.0+/-3.2 and 38.7+/-6.7 d in group D, E and F, respectively. CONCLUSION: 5-FUCI shows no obvious toxicities to gastrointestinal tract and myelotoxicity. After implantation, it kept a high level of 5- fluorouracil in surrounding tissues of the implant for eight weeks. Its antitumor effect on Walker-256 carcinosarcoma is demonstrated.

Relationship between nuclear morphometry, DNA content and resectability of pancreatic cancer.

AIM: To investigate the association of nuclear morphometry and DNA content with resectability of pancreatic cancer. METHODS: A total of 36 patients with pancreatic adenocarcinoma were divided into resectable group and unresectable group. The nuclear morphometry and DNA contents of tumor cells were analyzed by IBAS autoimagine analyzer from paraffin-embedded materials. Localization size, histological type and grade, and clinical stage of the tumor were evaluated. Factors influencing resectability of pancreatic cancer were investigated using stepwise regression analysis. RESULTS: Statistical significance was found in nuclear DNA content (integrated optical density, IOD) of tumor cells (1.64+/-0.41 vs 2.96+/-0.55), DNA ploidy, ages (46.5+/-5.3 years vs 58.6+/-0.7 years) and tumor volumes (298.1+/-101.5 cm(3) vs 634.7+/-512.5 cm(3)) in both groups (P<0.05), and no difference was found in the nuclear morphometry (P>0.05). The rates of diploid/tetraploid and aneuploid were 66.7 % and 33.3 % in resectable group respectively, and 38.9 % and 62.1 % in unresectable group, respectively (P<0.05). IOD (X(12)), ploidy status (X(12)) and clinical stage (X(3)) were radical resectable indicators with statistical significance. The regression equation for resectability was Y=-9.2053+3.5428X(12)+2.5390X(13)-2.3001X(3) (RR=0.8780, P<0.01). CONCLUSION: There is a high correlation between resectability of pancreatic cancers and their DNA contents, DNA ploidy status and clinical stage.

Influence of methionine/valine-depleted enteral nutrition on nucleic acid and protein metabolism in tumor-bearing rats.

AIM: To investigate the effects of methionine/valine-depleted enteral nutrition (EN) on RNA, DNA and protein metabolism in tumor-bearing (TB) rats. METHODS: Sprague-Dawlley (SD) rats underwent jejunostomy for nutritional support. A suspension of Walker-256 carcinosarcoma cells was subcutaneously inoculated. 48 TB rats were randomly divided in 4 groups: A, B, C and D. The TB rats had respectively received jejunal feedings supplemented with balanced amino acids, methionine-depleted, balanced amino acids and valine-depleted for 6 days before injection of 740 KBq (3)H- methionine/valine via jejunum. The (3)H incorporation rate of the radioactivity into RNA, DNA and proteins in tumor tissues at 0.5, 1, 2, 4 h postinjection of tracers was assessed with liquid scintillation counter. RESULTS: Incorporation of (3)H into proteins in groups B and D was (0.500+/-0.020) % to (3.670+/-0.110) % and (0.708+/-0.019) % to (3.813+/-0.076) % respectively, lower than in groups A ((0.659+/-0.055) % to (4.492+/-0.108) %) and C ((0.805+/-0.098) % to (4.180+/-0.018) %). Incorporation of (3)H into RNA, DNA in group B was (0.237+/-0.075) % and (0.231+/-0.052) % respectively, lower than in group A (P<0.01). There was no significant difference in uptake of (3)H by RNA and DNA between group C and D (P>0.05). CONCLUSION: Protein synthesis was inhibited by methionine/valine starvation in TB rats and nucleic acid synthesis was reduced after methionine depletion, thus resulting in suppression of tumor growth.