99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as potential radiotracers to target tumor hypoxia.

In this study, the commercially available secnidazole was successfully converted to secnidazole xanthate (SNXT), in which the xanthate group can act as a bifunctional chelator to coordinate with 99mTc. 99mTc-nitrido complex of SNXT(99mTcN-SNXT) and 99mTc-oxo complex of SNXT(99mTcO-SNXT) were prepared with high radiochemical purity. Both of the complexes were found to be stable in vitro and to exhibit similar hydrophilicity. In addition, comparative in vitro cell uptake studies under anoxic and normoxic conditions demonstrated that both agents were preferentially taken up by hypoxic cells. Biodistribution studies in mice bearing S180 tumor showed 99mTcO-SNXT exhibited a higher tumor uptake and tumor-to-muscle ratio than 99mTcN-SNXT. Furthermore, in SPECT imaging study, 99mTcO-SNXT exhibited a clear accumulation in tumor at 2 h post-injection, suggesting its potential to be a novel hypoxia imaging agent.

Study on antitumor, antioxidant and immunoregulatory activities of the purified polyphenols from pinecone of Pinus koraiensis on tumor-bearing S180 mice in vivo.

Pinecone polyphenols are bioactive dietary constituents that enhance health and help prevent and treat cancer through improving antioxidant and immunoregulatory activities. This study was designed to investigate the antitumor, antioxidant and immunoregulatory activities of the 40% ethanol eluent of polyphenols from pinecone of pinus koraiensis (PPP-40) in Sarcoma 180 (S180)-bearing mice models in vivo. The results of antitumor activity indicated that PPP-40 significantly inhibited S180 tumor growth and the dose of 150mg/kg exhibited the highest antitumor activity. Moreover, TdT-mediated dUTP nick end labeling (TUNEL) assay results further confirmed the apoptosis of S180 tumor cells. In addition, PPP-40 could obviously promote the expressions of Bax protein and inhibit the Bcl-2 protein, accordingly improve the expressions of activated Caspase-3 as well, which resulted in the activation of mitochondrial apoptotic pathway of tumor cells in S180 mice eventually. The results of antioxidant activity showed that the S180 mice treated with PPP-40 had the higher superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, the more glutathione (GSH) content, and the lower malondialdehyde (MDA) level in plasma comparing with non-treated control group. Moreover, the administration with PPP-40 (150mg/kg) significantly accelerated the proliferation of splenocytes (p<0.01) and increased the monocyte phagocytosis activity in vivo simultaneously. These results revealed that PPP-40 exerts an effective antitumor activity by activating the mitochondrial apoptotic pathway and improving the antioxidant and immunoregulatory activities.

Antitumor and immunomodulatory activities of a water-soluble polysaccharide from Chaenomeles speciosa.

In this study, a water-soluble polysaccharide (CSP) was successfully purified from Chaenomeles speciosa by DEAE-Sepharose and Sephadex G-100 column chromatography. CSP had a weight-average molecular weight of about 6.3 × 10(4)Da and was composed of glucose (Glc), galactose (Gal), rhamnose (Rha) and arabinose (Ara) with a relative molar ratio of 4.6:1.3:0.8:0.5. CSP could not only inhibit the growth of S180 tumor transplanted in mice, but also increase the relative spleen index and body weight of tumor bearing mice. Moreover, concanavalin A (ConA) and lipopolysaccharide (LPS) induced splenocyte proliferation and peritoneal macrophage phagocytosis were also enhanced after CSP administration. Furthermore, CSP treatment could improve delayed type hypersensitivity (DTH) and promote the secretion of IL-2, TNF-α and IFN-γ in serum. The overall findings suggest that the antitumor effect of CSP is might be associated with its potent immunostimulatory activity.

Improved tumor targetability of Tat-conjugated PAMAM dendrimers as a novel nanosized anti-tumor drug carrier.

The generation 4-poly-amidoamine-dendrimers (PAMAM G4 dendrimer, P) was conjugated to Tat peptide (Tat, T), a cell-penetrating peptide, in search of an efficient anti-tumor drug delivery vehicle for cancer therapy. In this study, we synthesized BODIPY-labeled Tat-Conjugated PAMAM dendrimers (BPTs) as a novel nanosized anticancer drug carriers and systemically investigated their biodistribution and the tumor accumulation in Sarcoma 180-bearing mice. In addition, the uptake and the cytotoxicity to S180 cells of BPTs thereof were evaluated. The unmodified dendrimer (BP) showed a soon clearance from the blood stream and nonspecific accumulation in tumor. In contrast, the Tat-modified dendrimer, BPT(64) with appropriate particle size showed a better retention in blood and could be accumulated effectively in tumor tissue via the enhanced permeability and retention (EPR) effect. Moreover, BPTs with a high Tat modification rate was accumulated more effectively in tumor tissue. In vitro experiments, these BPTs displayed low cytotoxicity on S180 cells and high uptake to S180 cells. These findings indicate that the nanoparticulate system on the basis of Tat-conjugated PAMAM dendrimers is safer and effective in the concentration range (below 20 µg/ml) to be used as a carrier of anti-tumor drugs for tumor targeting by intravenous administration.

[Experimental study on inhibitory effect of GFW on transplantable tumor cell metastasis in S180 tumor-bearing mices].

OBJECTIVE: To detect the effect of GFW on tumor cell metastasis in S180 tumor-bearing mice. METHOD: S180 tumor-bearing mice model were replicated and divided randomly into 4 groups: the model group, the GFW group, the cyclophosphamide group and the combination administration group. VEGF in serum on each group was detected by ELISA, and the expression of metastasis suppressor gene nm23H1 and cell adhesion molecule CD44 in Sarcoma were detected by SABC immunohistochemical assay. RESULT: Compared with the model group, the GFW group showed a significant decrease in VEGF in serum (P < 0.01). From their statistically significant difference, GFW was proved to promote the expression of metastasis suppressor gene nm23H1 and inhibit the expression of cell adhesion molecule CD44 (P < 0.05). CONCLUSION: GFW has an effect on inhibiting tumor metastasis to some extent.

[Effect of Flammulina velutipes polysaccharides on production of cytokines by murine immunocytes and serum levels of cytokines in tumor-bearing mice].

OBJECTIVE: To study the effect of Flammulina velutipes polysaccharides (FVP) on the production of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (INF-gamma) and interleukin 2 (IL-2) by murine immunocytes. METHODS: The cell's metabolic activity was determined with methylthiazolyl tetrazolium (MTT) colorimetry assay and the amounts of TNF-alpha, INF-gamma and IL-2 were measured by ELISA. RESULTS: FVP (200, 100, 50 microg/mL) could promote the metabolic activity of murine splenocytes and peritoneal exudate cells (PEC) and increase the amounts of TNF-alpha, INF-gamma and IL-2 in the supernatants of splenocyte cultures, and the amount of TNF-alpha in PEC cultures, with the most marked increase on TNF-alpha level. FVP (100, 50, 25 mg/kg) could raise the serum levels of TNF-alpha and INF-gamma in S180 tumor-bearing mice. CONCLUSION: FVP may regulate murine immune function through promoting the production of TNF-alpha, INF-gamma and IL-2.

[Changes of serum interferon-gamma levels in mice bearing S-180 tumor and the interventional effect of immunomodulators].

OBJECTIVE: To investigate the changes of serum inteferon-gamma (IFN-gamma) in mice bearing S-180 tumor and explore the role of the endogenous IFN-gamma in confining the transplanted tumor by intervention with immunomodulators. METHODS: Mouse models bearing S-180 solid tumor were established and subjected to intragastric administration of Ganoderma lucidum polysaccharides (GLP) or cyclosporine A (CsA) at different daily doses for 9 consecutive days. Serum IFN-gamma levels were measured in untreated tumor-bearing mice and in those after completion of GLP or CsA treatments by enzyme-linked immunosorbent assay (ELISA), and the changes of the tumor weight in the treated mice were evaluated. RESULTS: It was found for the first time that serum IFN-gamma levels in the tumor-bearing mice increased progressively within the initial 20 days after tumor implantation. The serum IFN-gamma levels in the 3 GLP-treated groups (at daily doses of 400, 200, and 100 mg/kg) all increased, which was the most obvious in 400 mg/kg GLP-treated group, and the tumor weight decreased significantly in response to GLP treatment, but the most conspicuous effect occurred with the daily dose of 200 mg/kg, and no significant statistical correlation was found between the two parameters. CsA treatment (at 20, 10, and 5 mg/kg, respectively) resulted in reduced serum IFN-gamma levels but produced virtually no effect on the tumor weight, and no obvious correlation was found between serum IFN-gamma level and the tumor weight. CONCLUSION: Increased serum IFN-gamma levels following GLP treatment are not significantly correlated to tumor growth inhibition in mice, and CsA reduces serum IFN-gamma levels without affecting the tumor weight, suggesting that endogenous IFN-gamma is not a major immunomodulating factor in growth inhibition of transplanted S-180 tumor.

[Effect of Patrinia scabra extracts on the level of serum cytokine in sarcoma 180 ascitic tumor burdened mice].

OBJECTIVE: To explore the effect of Potrinia scabro extracts (PSE) on the level of serum cytokine in Sarcoma 180 ascitic tumor burdened mice and its mechanism of anti-tumor. METHODS: The mice model of Sarcoma 180 ascitic tumor were established and divided into five groups randomly, including the model group with normal saline solution, the positive group with 10 mg/kg cytoxan and PSE treated groups at doses of 2.0 g/kg, 1.0 g/kg, 0.5 g/kg intraperitoneally for 10 days. The level of serum cytokine Th1 (IL-2, IL-12, IFN-gamma, IFN-alpha) and Th2 (IL-6, IL-10) were measured by double antibody sandwich ELISA assay. RESULTS: Compared with model group of Sarcoma 180 ascitic tumor burdened mice,the level of IL-2 and IFN-gamma increased in PSE 2.0 g/kg group, but the IL-6 and IL-10 decreased in PSE 2.0 g/kg and 1.0 mg/kg groups. CONCLUSION: PSE has anti-tumor effect in vivo that could be related to the level variation of IL-2, IFN-gamma, IL-6 and IL-10 in tumor burdened mice.

[Anti-cancer activity of Zuojinwan in vivo and influence to tumor markers in mice transplanted with sarcoma 180].

OBJECTIVE: To study the anticancer action of Zuojinwan in mice transplanted with sarcoma 180 in vivo, and detect the activities of five kinds of tumor markers (TM) including acid phosphotase (ACP), alkaline phosphotase (AKP), creatine kinase (CK), aldolase (ALD) and lactate dehydrogenase (LDH) in serum compared with Coptis chinensis and Evodia rutaecarpa. METHOD: The transplanted S180 tumor mice model was established, and the mice were divided randomly five groups. The extract of Zuojinwan (850.8 mg kg(-1)), C. chinensis (729.2 mg kg(-1)) and E. rutaecarpa (121.6 mg kg(-1)) were administrated, respectively for 10 d. Then, the changes of body weight, spleen index of mice, the inhibition rates of tumor, and the increase of life span (ILS) were all tested. In addition, the activities of ACP, AKP, CK, ALD and LDH on different test groups were also determined. RESULT: Zuojinwan could inhibit the S180 tumor growth significantly with the inhibition rate of 50.54% and the ILS of mice reached to 64.91%. Meanwhile, the activities of ACP (126.72 +/- 11.16) U 100 mL(-1) and AKP (67.27 +/- 13.49) U 100 mL(-1) were increased, and the activities of CK (20.65 +/- 4.28) U mL(-1), ALD (319.13 +/- 53.87) U L(-1) and LDH (1,029.04 +/- 468.56) U L(-1) were decreased significantly by Zuojinwan treated group compared with C. chinensis and E. rutaecarpa treated groups (P<0.01). CONCLUSION: In the prescription of Zuojinwan, the enhancement of compatibility of anticancer activity was observed by the interaction of C. chinensis and E. rutaecarpa. The mechanism might be in according with to influence the activities of the five kinds of tumor markers (TM) in mice serum.

[Inhibitory effect of combined bacterin on growth of sarcoma 180 in mice].

BACKGROUND & OBJECTIVE: It was reported that the symptoms of tumor patients may be alleviated markedly and even the tumor may be regressed completely after acute infection. Bacterin OK-432 has notable inhibitory effect on the growth of various tumors in animals. At present, OK-432 has been used in clinical immunotherapy for tumors with no other adverse events besides fever and leucocytosis. This study was to investigate the effects of combined bacterin on the serum level of interleukin 12(p70)[IL-12(p70)] and the growth of sarcoma 180 (S180) in mice. METHODS: After transplantation of S180, the mice were randomized into 5 groups, and received injection of Staphylococcus aureus, Salmonella typhimurium, Mycobacteria phlei, and combined bacterin containing the 3 bacteria strains, respectively, or received no treatment (blank control). The weight of S180 xenografts, the thymus, and the spleen in mice was measured. The serum level of IL-12(p70) was detected by ELISA. RESULTS: The mean weight of S180 tumors was 1.39 g in Staphylococcus aureus group, 1.50 g in Salmonella typhimurium group, 1.36 g in Mycobacteria phlei group, 0.62 g in combined bacterin group, and 2.40 g in blank control group; the differences among the 5 groups were significant (F=66.73, P<0.001). The mean weight of S180 tumors was significantly lower in the 4 bacterin groups than in control group, and significantly lower in combined bacterin group than in the 3 single bacterin groups (q test, P<0.001). The weights of the thymus and the spleen among the 5 groups had no significant difference (F=2.36, P>0.05; F=1.89, P>0.05). The inhibition rate of tumor growth was significantly higher in combined bacterin group than in Staphylococcus aureus, Salmonella typhimurium, and Mycobacteria phlei groups (74.17% vs. 42.08%, 37.50%, and 43.33%, P<0.01). The mean serum level of IL-12(p70) was 19.44 pg/ml in combined bacterin group, 12.41 pg/ml in Staphylococcus aureus group, 10.35 pg/ml in Salmonella typhimurium group, 11.68 pg/ml in Mycobacteria phlei group, and 4.45 pg/ml in control group; the difference among the 5 groups was significant (F=15.76, P<0.0001), but the difference among the 3 single bacterin groups was not significant (q test, P>0.05), while the differences between other groups were significant (q test, P<0.01). CONCLUSIONS: The chosen bacterins in this study can induce the mice to produce IL-12(p70) and suppress the growth of S180. The effect of the combined bacterin is much better than the single bacterins.

Analysis in vivo of antitumor activity, cytotoxicity and Interaction between plasmid DNA and the cis-dichloro-tetra-amine-ruthenium(III) chloride.

Several metallic compounds recognized as potent antitumor agents, have been developed and tested in vivo and in vitro. In this work, we evaluated the toxic, therapeutic, and cytotoxic properties of the cis-dichloro-tetra-amine-ruthenium(III) chloride. Transplanted animals with Sarcoma 180 cells were treated with ruthenium(III) complex and injected i.p., at different time intervals. After the 15th day, tumoral postimplant, the animals were sacrificed and their lungs, kidneys, liver, and tumors were removed and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses. Interaction between the ruthenium complex and the DNA was also investigated. Besides being cytotoxic for the S180 cells, the metallic compound induced tumoral volume reduction and increased survival time of the animals treated. Serum levels of LDH, creatinine, and bilirubin increased, but no serious irreversible histopathological alterations were observed in the analyzed tissues. The compound did not cause anemia, but reduced the number of leukocytes in the treated animals. The absence of viable S180 cells, necrotic cells, and the presence of granulation tissue were observed in tumor tissue of treated animals. The Ru(III) complex, in the presence of the reduction agent, caused plasmid DNA to fragment. These results suggest that cis-RuCl(2)(NH(3))(4)Cl compound is a potent antitumoral drug in vitro and in vivo, which seems to involve binding to DNA molecule.

Direct comparison of two pegylated liposomal doxorubicin formulations: is AUC predictive for toxicity and efficacy?

Rationally designed liposomes could improve the therapeutic indexes of chemotherapeutic drugs, which is due to alterations in the pharmacokinetics and biodistribution of encapsulated drugs. For traditional drug delivery systems, the accumulation of drugs in healthy and malignant tissues could be correlated with toxicity and efficacy. Some previous studies also indicate that the higher tumor AUC, the better therapeutic efficacy, suggestive of the possible existence of positive correlation. Are AUC values of liposomal drugs really predictive? For the purpose to address this question, we designed two pegylated liposomal doxorubicin formulations (PLD-75 and PLD-100), which had the same lipid/drug ratio and bilayer composition, but different size and internal ammonium sulfate concentration. In vitro drug retention experiments revealed that drug was released at a faster rate from PLD-75, a small size formulation. The plasma pharmacokinetics of PLD-75 was similar to that of PLD-100, regardless of whether the mice were tumor-free or not. It should be noted, though, that in tumor-bearing mice the plasma doxorubicin level in PLD-75 group was only about 59% of that in PLD-100 group at 48 h post injection. Furthermore, their biodistribution behavior in S-180 tumor-bearing KM mice was significantly different. Compared with animals receiving PLD-100, those receiving PLD-75 showed a 19.2%, 27.8%, and 23.5% decrease in liver (p<0.01), spleen (p<0.001) and lung (p<0.05) AUC, respectively. In other healthy tissues except kidney, the drug deposition also reduced by 10-15%, but the difference was not significant. The tumor AUC after administration of PLD-100 and PLD-75 were 1285.3 ugh/g and 762.0 ugh/g, respectively (p<0.001). Maximum drug levels achieved in the tumors were 33.80 microg/g (for PLD-100) and 20.85 microg/g (for PLD-75), and peak tumor concentration was achieved faster in PLD-75 group. However, enhanced drug accumulation does not mean increased antineoplastic effect, and at the same doxorubicin dose level, PLD-75 was more efficacious. As for toxicity studies, PLD-75 caused more rapid and severe body weight loss despite the fact that drug accumulation in healthy tissues was reduced. Our data indicate that liposomal systems are more complicated than conventional drug delivery systems, and it is hard to predict the toxicity and efficacy of liposomal drugs through the measure of liposomal drug accumulation.

[Erythrocyte immunologic function effects of Patrinia scabra extracts by macroporous adsorptive resins on mice burdened transplanted tumor].

OBJECTIVE: To research the erythrocyte immunoregulation effects of Patrinia scabra extracts by macroporous adsorptive resins on mice burdened transplanted tumor. METHODS: Extracts of Patrinia scabra Bunge were separated by macroporous adsorptive resins, ingredients were analysised. Mice burdened transplanted tumor were given extracted drugs. Life prolongation rate was observed, erythrocyte immunologic function and the CD35, CD44s contents of red blood cell were evaluated. RESULTS: Polysaccharide and saponin accounted for 8.4% and 48.4%. Extracts could porolong life expectancy of mice, improve erythrocyte immunolgic function and increase the CD35 and CD44s contents of red blood cell. CONCLUSION: Extracts of Patrinia scabra Bunge by macroporous adsorptive resins have erythrocyte immunoregulation effects on mice burdened transplanted tumor.

[Experimental study on anti-tumor effect of extractive from Celastrus orbiculatus in vivo].

OBJECTIVE: To study the anti-tumor activity of extractive from Celastrus orbiculatus in vivo. METHOD: Mice bearing transplanted tumor S180 and Heps were used to study the effects of acetoacetate and n-butanol extractive from C. orbiculatus. The changes in serum contents of SOD and malondialdehyde (MDA) content were assayed. RESULT: Acetoacetate and n-butanol extractive from C. orbiculatus significantly inhibited the growth of S180 and Heps tumor in mice. SOD content was obviously increased, MDA content obviously decreased in the serum after extractive treatment. CONCLUSION: Acetoacetate and n-butanol extractive from C. orbiculatus have anti-tumor effects and anti-oxidative capacity.

The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo.

The anticancer effects of wogonin on murine sarcoma S180 both in vitro and in vivo were investigated, and its pro-apoptotic molecular mechanism was further studied. Wogonin treatment resulted in significant inhibition of S180 cells in a concentration-dependent manner detected by MTT assay. The IC50 value for 48 h was (7.37+/-1.53) x 10(-5) M. Typical morphological changes and apoptosis bleb phenomenon in S180 cells exposed to wogonin were distinctly observed by the inverted light microscope and the fluorescence microscope, respectively. According to protocols of transplanted tumor research, mice were transplanted with tumor cells S180. The weight of tumor and the peripheral leucocyte count were observed after the treatment of wogonin. The significant suppression of tumor growth was observed, and the peripheral leucocyte count of S180-bearing mice remained no significant changes compared with control group. After the treatment of 40 mg/kg wogonin, the inhibitory rate of tumor weight was 53.01%. Additional DNA fragmentation assay showed that wogonin induced apoptosis on murine sarcoma S180 tissue. RT-PCR results indicated that the increasing mRNA levels of bax and p53 and the decreasing mRNA level of bcl-2 were induced by wogonin. Western-blot assay showed that the increasing protein level of bax and the decreasing protein level of bcl-2 were induced by wogonin. Collectively, wogonin could induce apoptosis in murine sarcoma S180 thereby inhibiting the tumor growth both in vitro and in vivo. The pro-apoptotic effects might be related to the improvement of mRNA level of p53, the improvement of mRNA and protein levels of bax, and the reduction of mRNA and protein levels of bcl-2.

In vivo tumor targeting of tumor necrosis factor-alpha-loaded stealth nanoparticles: effect of MePEG molecular weight and particle size.

The aim of this study is to reveal the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size of stealth nanoparticles on their in vivo tumor targeting properties. Three sizes (80, 170 and 240nm) of poly methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA) nanoparticles loading recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) were prepared at different MePEG molecular weights (MW=2000, 5000 and 10,000) using double emulsion method. The opsonization in mouse serum was evaluated by Coomassie brilliant blue staining of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Phagocytosis was evaluated by incubating (125)I-rHuTNF-alpha-loaded nanoparticles with mouse macrophages (RAW264.7). The pharmacokinetics, biodistribution and tumor targeting studies were performed in S-180 tumor-bearing mice. Higher MePEG molecular weight provided thicker fixed aqueous layer thickness (FALT) and smaller particle size offered higher surface MePEG density. The serum protein adsorption and phagocytic uptake were markedly decreased for the nanoparticles with higher MePEG molecular weight or smaller size. The particles (80nm) made of PEG(5000)-PHDCA, possessing a thicker FALT (5.16nm) and a shortest distance (0.87nm) between two neighboring MePEG chains, showed the strongest capacity of decreasing protein adsorption and phagocytic uptake. These particles extended the half-life of rHuTNF-alpha in S-180 tumor-bearing mice by 24-fold (from 28.2 min to 11.33 h), elevated the rHuTNF-alpha peak concentration in S-180 tumors by 2.85-fold and increased the area under the intratumoral rHuTNF-alpha concentration curve by 7.44-fold. The results of the present study showed PEG-PHDCA nanoparticles with higher MePEG molecular weight and smaller particle size could achieve higher in vivo tumor targeting efficiency.

Effects of low-dose radiation on tumor growth, erythrocyte immune function and SOD activity in tumor-bearing mice.

BACKGROUND: Activating on mammalian and human body LDR is thought to induce adaptive response, enhance immune function and increase anti-tumor ability. This study was designed to assess the effect of low-dose radiation on tumor growth and on erythrocyte immune function and superoxide dismutase (SOD) activity in tumor-bearing mice. METHODS: Male Kunming mice were subcutaneously implanted with S180 sarcoma cells in the right inguen to create an experimental in situ animal model. Six hours before implantation, the mice were given 75 mGy X-ray radiation, over the body. Tumor size was observed 5 days later while tumor volume was calculated every other day, allowing for the creation of a graph depicting tumor growth. Fifteen days after implantation, the mice were killed to measure tumor weight and observe the necrotic areas and the location of tumor-infiltrating lymphocytes (TILs). Erythrocyte immune function and SOD activity were also determined. RESULTS: Mice pre-exposed to low-dose radiation had a lower tumor formation rate than did those receiving no radiation (P < 0.05). Tumor growth was significantly lower in the mice pre-exposed to low-dose radiation; after 15 days, the average tumor weight in the mice pre-exposed to low-dose radiation was also lower (P < 0.05). Areas of tumor necrosis and infiltration of TILs were larger in the low-dose radiation group than in the non-radiation group. Erythrocyte immune function and SOD activity were higher in the low-dose radiation group than in the non-radiation group (P < 0.05). CONCLUSION: Low-dose radiation can markedly increase the anti-tumor ability of an organism and improve erythrocyte immune function and red blood cell SOD activity as well, suggesting that low-dose radiation might be useful in the clinical treatment of cancer.

A general survey of glutamine level in different tissues of murine solid tumor bearing mice before and after therapy with purified glutaminase.

Distribution of glutamine level in different tissues of tumor bearing mice such as brain, liver, kidney, spleen, large and small intestine and the tumor itself were studied in three solid tumor models, viz, Ehrlich ascites carcinoma, Sarcoma-180 and methylcholanthrene induced carcinoma. Tumor bearing mice were subjected to therapy for 7 days with the glutaminase purified from malignant S-180 cell. The results exhibit a significant decrease in tumor burden after enzyme therapy. Host tissue glutamine levels were significantly elevated in tumor bearing untreated mice in comparison to the normal ones, while significant lower values were obtained after enzyme therapy. It therefore appears that elevated levels of glutamine in host tissue are associated with the tumor burden.

[Study on inhibition and prevention of tumor and antioxidative effects of lithium carbonate in tumor bearing mice].

Two Kinds of tumor-bearing mice (hepatoma H22 and sarcoma S180) were administered with lithium carbonate (Li2CO3) for 17 or 10 days (advanced and simultaneous administration), in order to observe the effects of prevention and treatment of Li2CO3 on malignant tumor, as well as the relationship between Li2CO3 and lipid peroxidation in tumor-bearing mice. Meanwhile, we compared the toxic and side effects of cyclophosphamide (CP) with that of Li2CO3. The results showed that Li2CO3 had no significant toxic or side effects with the suggested doses. In the tests of inhibition and prevention of tumor, Li2CO3 could significantly inhibit the grouth of the two kinds of tumor, and increase the activity of superoxide dismutage (SOD) and decrease the contents of Malonyldialdehyde (MDA). In addition, Li2CO3 had no effect on the white blood cells (WBC) and decreased the micronucleus frequency (MNF) in bone marrow polychromatic erythrocytes (PCE), while CP had definite effect of decreasing the WBC and increasing the MNF in the tumor-bearing mice.

Antitumor activity of hydroxythiamine and methotrexate immobilized on monocarboxycellulose.

The aim of the present study was to examine the antitumor and antivitamin activities of some new combinations of methotrexate (MT) and hydroxythiamine (HT), antagonists of folic acid and thiamine, respectively, immobilized on monocarboxycellulose (MCC). Ehrlich ascites carcinoma and sarcoma 180 were used as test malignant tumors in mice. It has been shown, that the compounds studied decreased significantly the amount of mitotically dividing tumor cells and increased the percentage of dead cells, inhibited the tumor growth (up to 10-30 fold at the early stage of neoplasm development) and elongated the life-span of tumor-bearing animals (by 1.6-3.3-fold) as compared to the control. All MCC-immobilized HT and MT complexes studied demonstrated higher antitumor efficacy compared to the mixture of these drugs or each of the agents applied individually. The specific feature of the newly synthesized substances was strong and prolonged antitumor effect following single administration. The severity of thiamine and folic acid deficiencies essentially depended on the amount of HT and MT in the preparations. A close correlation was found between the inhibition of transketolase in the tumors and the antiblastoma properties of the preparations. It enables us to suggest, that the antithiamine action of these preparations is one of the important factors in the mechanism of their antitumor effect.