The effect of antioxidants in Ehrlich Ascites Cancer.

A fundamental goal in molecular oncology is to unravel the underlying mechanisms which cause the cell transformation. In line with this approach, genome-wide functional screening approaches have revealed exciting insights into heterogeneous nature of cancer. Rapidly expanding horizons of research have unraveled myriad of pathways which play instrumental role in carcinogenesis and metastasis. Oxidative stress has also been reported to be significantly involved in cancer onset and progression. In line with this approach, oxidative stress modulating chemicals have always been sharply divided into antioxidants and oxidative stress-inducing agents. Conceptual and experimental advancements have enabled us to critically analyze full potential of these two different groups of chemicals in cancer chemoprevention. Different antioxidants are currently being analyzed in different phases of clinical trials. Although it has been reported in the literature that antioxidant supplements reduce tumor cells in some tumors or cause volume reduction in solid tumor sizes, there is no definite consensus. Therefore, an antioxidant supplement guideline based on more detailed clinical research and as a result of these is needed to achieve the best care for cancer patients and to avoid risky treatments for cancer patients.

Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts.

CONTEXT: Abnormal angiogenesis and evasion of apoptosis are hallmarks of cancer. Accordingly, anti-angiogenic and pro-apoptotic therapies are effective strategies for cancer treatment. Medicinal plants, namely, Eugenia jambolana Lam. (Myrtaceae), Musa paradisiaca L. (Musaceae), and Coccinia indica Wight & Arn. (Cucurbitaceae), have not been greatly investigated for their anticancer potential. OBJECTIVE: We investigated the anti-angiogenic and pro-apoptotic efficacy of ethyl acetate (EA) and n-butanol (NB) extracts of E. jambolana (seeds), EA extracts of M. paradisiaca (roots) and C. indica (leaves) with respect to mammary neoplasia. MATERIALS AND METHODS: Effect of extracts (2-200 µg/mL) on cytotoxicity and MCF-7, MDA-MB-231 and endothelial cell (EC) proliferation and in vitro angiogenesis were evaluated by MTT, 3[H]thymidine uptake and EC tube formation assays, respectively. In vivo tumour proliferation, VEGF secretion and angiogenesis were assessed using the Ehrlich ascites tumour (EAT) model followed by rat corneal micro-pocket and chicken chorioallantoic membrane (CAM) assays. Apoptosis induction was assessed by morphological and cell cycle analysis. RESULTS: EA extracts of E. jambolana and M. paradisiaca exhibited the highest cytotoxicity (IC50 25 and 60 µg/mL), inhibited cell proliferation (up to 81%), and tube formation (83% and 76%). In vivo treatment reduced body weight (50%); cell number (16.5- and 14.7-fold), secreted VEGF (∼90%), neoangiogenesis in rat cornea (2.5- and 1.5-fold) and CAM (3- and 1.6-fold) besides EAT cells accumulation in sub-G1 phase (20% and 18.38%), respectively. DISCUSSION AND CONCLUSION: Considering the potent anti-angiogenic and pro-apoptotic properties, lead molecules from EA extracts of E. jambolana and M. paradisiaca can be developed into anticancer drugs.

Effect of double-stranded DNA on maturation of dendritic cells in vitro.

A preparation of human genomic fragmented double-stranded DNA (dsDNA) was used as maturation stimulus in cultures of human dendritic cells (DCs) generated in compliance with the interferon protocol. Culturing of the DCs in medium with 5µg/ml of the DNA preparation was associated with a decrease in the relative proportion of CD14 + cells and an increase in that of CD83 + cells. These changes are markers of DC maturation. The efficiency with which the DNA preparation was able to elicit DC maturation was commensurate with that of lypopolysaccharide from bacterial cell, the standard inducer of DC maturation. Generated ex vivo, matured in the presence of the human DNA preparation, pulsed with tumor antigens mouse DCs were used as a vaccine in biological tests for its antitumor activity. The experimental results demonstrate that reinfusion of mature pulsed with tumor antigens DCs cause a statistically significant suppression of tumor graft growth.

Prominent chemopreventive and chemoenhancing effects for resveratrol: unraveling molecular targets and the role of C-reactive protein.

BACKGROUND: Resveratrol (RSVL) claims health benefits that pertain to the consumption of red wine/grapes. We currently evaluated the chemopreventive effects of RSVL, as well as its possible chemoenhancing effects when given with cisplatin (CP), in the Ehrlich ascites carcinoma (EAC) solid tumor model. Further, we monitored concomitant changes in serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), leukocytic count (LC) and lipid peroxidation (measured as malondialdehyde, MDA). RESULTS: EAC-bearing mice exhibited a markedly elevated LC (2 fold), CRP (11 fold) and MDA levels (2.7 fold). RSVL (20 or 40 mg/kg) elicited significant, dose-dependent reductions in tumor size (58 and 78%, respectively), as well as in LC (normalized), CRP (down to 2 fold), TNF-alpha (down to near control levels) and MDA levels (normalized). The chemopreventive effects for CP (55% reduction in cell growth) was significantly lower than that of RSVL (40 mg/kg, 79% inhibition). Interestingly, coadministration of RSVL (20 mg/kg) markedly enhanced the chemoprevention of CP. Correlation studies revealed a high degree of positive association between tumor growth and CRP (r = 0.89) and leukocytosis (r = 0.86), thus attesting to a diagnostic/prognostic role for CRP in this solid tumor. CONCLUSION: RSVL elicited remarkable cytotoxicity on its own and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels. RSVL acts prominently by reducing inflammatory cytokines, leukocytosis and oxidative stress.

Vaccination with gamma radiation-attenuated Toxoplasma gondii protects against ovarian infiltration in mice-bearing Ehrlich ascites carcinoma.

Purpose: Cancer is one of the most common causes of mortality and morbidity worldwide. Vaccines have been emerged as an attractive approach for their capacity of eliciting long-term immune response targeting cancer cells. Attenuated avirulent Toxoplasma gondii stimulate immunity and activate antitumor cells thereby eliciting rejection of some established cancer. The purpose of this study was to evaluate the antitumor-protective capacity of vaccination with gamma radiation-attenuated T. gondii against ovarian penetration in Ehrlich ascites carcinoma (EAC)-bearing mice.Materials and methods: Forty-five mice were randomly divided into three groups as follows: nontumor-bearing (normal control); EAC-bearing group (EAC); and mice vaccinated orally with gamma radiation-attenuated T. gondii then inoculated 2 weeks later with EAC (TG + EAC). Survival rate, serum interleukin-12 (IL-12), and levels of IFN-γ mRNA, CD4, and CD8 in ovarian tissues homogenate were assessed. Also, ovarian histopathology and immunohistochemical expressions of metalloproteinase-2, CD34, and vimentin were determined.Results: The group vaccinated with attenuated T. gondii showed significantly increased survival rates, serum IL-12, and levels of IFN-γ, CD4, and CD8 in ovarian tissue homogenates as well as an enhancement of histopathological and immunohistochemical changes compared to EAC-bearing group.Conclusion: Vaccination with gamma radiation-attenuated T. gondii has the capacity to supply immunoprotective impact against ovarian invasion in EAC-bearing mice.

Gamma Radiation-Attenuated Toxoplasma gondii Provokes Apoptosis in Ehrlich Ascites Carcinoma-Bearing Mice Generating Long-Lasting Immunity.

PURPOSE: Pathological angiogenesis and apoptosis evasions are common hallmarks of cancer. A different approach to the antitumor effect of parasitic diseases caused by certain protozoans and helminthes had been adopted in recent years as they can affect many cancer characteristics. The present work is an attempt to assess the effect of gamma radiation-attenuated Toxoplasma gondii ME49 as an antiapoptotic and angiogenic regulator modifier on tumor growth aimed at improving cancer protective protocols. METHODS: Attenuated Toxoplasma gondii ME49 was administered orally to mice 2 weeks before inoculation with Ehrlich ascites carcinoma to allow stimulation of the immune response. Hepatic histopathology and immune responses were determined for each group. RESULTS: Marked suppression of the tumor proliferation with induction of long-lasting immunity by stimulating interferon γ and downregulating transforming growth factor ß. The level of tumor promoting inflammatory markers (STAT-3 and tumor necrosis factor α), the angiogenic factors (vascular endothelial growth factor A, integrin, and matrix metallopeptidase 2 and matrix metallopeptidase 9), as well as nitric oxide concentration were significantly decreased. This was collimated with an improvement in apoptotic regulators (cytochrome-c, Bax, Bak, and caspase 3) in liver tissues of vaccinated mice group compared to Ehrlich ascites carcinoma-bearing one. Moreover, the histopathological investigations confirmed this improvement. CONCLUSION: Hence, there is an evidence of potency of radiation attenuated Toxoplasma vaccine in immune activation and targeting tumor cell that can be used as a prophylactic or an adjuvant in combination with chemotherapeutic drugs.

Phycobiliprotein-mediated synthesis of biogenic silver nanoparticles, characterization, in vitro and in vivo assessment of anticancer activities.

Phycoerythrin is the main phycobiliprotein that responsible for harvesting light for photosynthesis in cyanobacteria. In this research, phycoerythrin extracted from the cyanobacterium Nostoc carneum has been used to reduce silver nitrate for silver nanoparticles (AgNPs) biosynthesis. UV-visible spectrophotometry for measuring surface plasmon resonance showed a single absorption peak at 430 nm, which confirmed the presence of AgNPs. The face-centered central composite design was chosen to evaluate the interaction effects between four process variables and also to determine their optimal levels which influence the AgNPs biosynthesis using phycoerythrin. The maximum silver nanoparticles biosynthesis (1733.260 ± 21 µg/mL) was achieved in the central runs under the conditions of initial pH 10, incubation period of the 24 h, phycoerythrin concentration of the 0.8 mg/mL and 20 mM of AgNO3. The biosynthesized AgNPs were characterized using TEM which revealed the formation of spherical shape nanoparticles with size ranged between 7.1‒26.68 nm. EDX analysis confirmed silver as the major constituent element. FTIR spectrum indicates the presence of proteinaceous capping agent that prevents silver nanoparticles agglomeration. The IC50 of cell inhibition by AgNPs was observed at 13.07 ± 1.1 µg/mL. Treatment of mice bearing Ehrlich ascites carcinoma with 5 mg AgNPs/kg of mice body weight significantly decreased tumor volume, tumor cells count, white blood cells count and body weight. It was concluded that the phycoerythrin protein has the ability to synthesize AgNPs, which have antibacterial, antihemolytic, in vitro and in vivo cytotoxic activities.

Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT signaling pathway: protection by black tea.

Down-regulation of cell-mediated immune functions occurring at late stages of cancer may be related to the thymic involution since thymus is the major site of T cell maturation, proliferation, and differentiation. We found that in Ehrlich's ascites carcinoma (EAC)-bearing mice there was profound depletion of CD4+ and CD8+ cells in peripheral blood with severely damaged thymus on 21st day of tumor inoculation. However, treatment with black tea at an antitumor dose of 2.5% significantly reduced such depletion and protected the thymus considerably from tumor onslaught. A search for the underlying mechanism revealed EAC-induced IL-7Ralpha down-regulation, inhibition of JAK3 and STAT5 phosphorylation, and decrease in Bcl-2/Bax ratio in thymocytes that finally led to thymocyte apoptosis in one hand and T cell maturation block on the other. Interestingly, black tea treatment prevented IL-7Ralpha down-regulation and protected the signaling cascade through JAK-STAT thereby inhibiting tumor-induced thymic apoptosis and ensuring proper functioning of this organ in tumor-bearing host.

Suppression of Ehrlich ascites tumors in mice by minute virus of mice.

As a model system to study parvoviral oncosuppression, Ehrlich ascites (EA) cells were injected into the peritoneal cavities of ICR mice, and the effect of im injection of minute virus of mice (MVM) on EA tumor growth was examined. Coinjection with MVM resulted in a dramatic inhibition of EA tumor formation. Tumor suppression required viable, infectious virus. Mice that had survived one EA-MVM coinjection acquired long-term resistance to additional injections of EA cells.

Use of raw Euphorbia tirucalli extract for inhibition of ascitic Ehrlich tumor.

OBJECTIVE: to evaluate the effect of the Euphorbia tirucalli hydroalcoholic extract (ETHE) on the development of Ehrlich Tumor, in its ascitic form. METHODS: we intraperitoneally inoculated 15 Swiss mice with 10.44 x 107 cells of Ehrlich Tumor and divided them in two groups one day after: ETHE Group (eight mice), treated with a dosage of 125 mg/kg/day of EHTE for five days; and Control Group (seven mice), treated only with 0.9% isotonic saline solution over the same period. The treatment was done by gavage. Ten days after inoculation, four mice from each group were sacrificed for quantification of tumor cell number, ascitic fluid volume and bone marrow cell number. The remaining animals were maintained to evaluate survival. RESULTS: The ascitic fluid volume and the tumor cell number were decreased in the ETHE group when compared with the control group, but with no statistical significance. On the other hand, survival was higher in the ETHE group, as well as the number of bone marrow cells. CONCLUSION: Treatment with ETHE after inoculation of Ehrlich Tumor decreases its development and increases survival and the bone marrow cellularity, thus reducing the myelosuppression present in the Ehrlich Tumor bearing mice.

Enhanced immune response to gastric cancer specific antigen Peptide by coencapsulation with CpG oligodeoxynucleotides in nanoemulsion.

CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant activity for a wide range of antigens. Of particular interest is their improved activity when closely associated with the antigen. The purpose of this study is to construct a nanovaccine coencapsulated with a gastric cancer specific antigen MG7 mimotope peptide and adjuvant CpG ODN 1645 using new nanotechnology as nanoemulsion and evaluate its immunocompetence. Nanoemulsion vaccine was prepared using magnetic ultrasound methods. BALB/c mice were immunized and the in vivo effectiveness was evaluated using tumor challenge assay. It was shown that the tumor masses formed in the mice immunized with coencapsulated nanovaccine (0.0825 g) markedly smaller (P < 0.01) than those formed in the mice immunized with nanovaccine encapsulated with antigen peptide alone (0.4465 g). A tumor inhibiting rate as high as 82.5% of the coencapsulated nanovaccine was obtained, while nanovaccine encapsulated with peptide only could not achieve the same effect (28.5%) (P < 0.01). Enzyme-linked immunospot assay (ELISPOT) showed that immunization using MG7 mimotope peptide coencapsulated with CpG ODN within the same nanoemulsion enhanced the frequency of splenocytes secreting IFN-gamma significantly (P < 0.01) when compared with immunization using MG7 peptide encapsulated in nanoemulsion alone (197spots/1 x 10(6) vs. 73 spots/1 x 10(6)). Cellular ELISA indicated that serum titer of antibody against MG7-Ag was significantly higher (P < 0.01) in mice immunized with coencapsulation form nanovaccine (0.7884) than that in the group immunized with nanovaccine encapsulated with MG7 peptide alone (0.3616). Using intracellular flow cytometric analysis, it was found that the IFN-gamma response was contributed by CD4+ T-cells. Our experiments suggest that a vaccinal approach using nano-delivery system carrying in tumoral epitope and CpG ODN as adjuvant may have important implications for cancer therapy.

Oral attenuated Salmonella typhimurium vaccine against MG7-Ag mimotope of gastric cancer.

AIM: To develop an oral attenuated Salmonella typhimurium vaccine against gastric cancer and to evaluate its efficacy in mice. METHODS: A complementary sequence of Nco I site and a sequence coding for MG7-Ag mimotope were designed at the 5' terminus of forward primer. Using p1.2 II-HBCAg plasmid as template, PCR was performed to get a fusion gene of the mimotope and a HBcAg gene. The fusion gene was then subcloned into the plasmid pYA3341 complementary to Salmonella typhimurium X4550, and the recombinant plasmid was then transformed into attenuated Salmonella typhimurium X4550. Balb/c mice were orally immunized with the recombinant Salmonella typhimurium X4550. The mice were immunized every 2 wk to reinforce the immunity. At the 6th wk, serum titer of antibody was detected by ELISA, and at the 8th wk, cellular immunity was detected by (51)Cr release test. Ehrlich ascites carcinoma cells expressing MG7-Ag were used in tumor challenge assay as a model to evaluate the protective effect of the vaccine. RESULTS: Serum titer of antibody against MG7-Ag was significantly higher in mice immunized with the vaccine than in control groups (0.9538+/-0.043 vs 0.6531+/-0.018, P<0.01; 0.9538+/-0.043 vs 0.6915+/-0.012, P<0.01), while in vitro (51)Cr release assay of the splenocytes showed no statistical difference in the three groups. Two weeks after tumor challenge, 1 in 5 immunized mice was tumor free, while all the mice in the control group presented tumor. CONCLUSION: Oral attenuated Salmonella typhimurium vaccine against the MG7-Ag mimotope of gastric cancer is immunogenic. It can induce significant humoral immunity against tumors in mice, and has some protective effects.

Chemopreventive effect of leflunomide against Ehrlich's solid tumor grown in mice: Effect on EGF and EGFR expression and tumor proliferation.

UNLABELLED: i) AIMS: The current study aimed to examine the effect of leflunomide on tumoral expression of epidermal growth factor and its receptor (EGFR) in Ehrlich's ascites carcinoma (EAC) grown in mice. ii) MATERIALS AND METHODS: Mice were injected subcutaneously with EAC cells and allocated into four groups; Group i: EAC control group. Groups ii-iv: mice treated with leflunomide (3, 10 or 30mg/kg/day, p.o.), respectively. Pharmacologic treatments were initiated at day 8 and continued for 14days. iii) KEY FINDINGS: Treatment with leflunomide evoked antitumor properties as indicated by reduction in tumor mass, histopathological score, number of intratumoral PCNA immunopositive nuclei. Leflunomide (3, 10 or 30mg/kg) exerted an anti-inflammatory effect as indicated by the reduction in serum tumor necrosis factor-α. Furthermore, leflunomide demonstrated anti-angiogenic activity which was expressed as a decline in serum vascular endothelial growth factor and down-regulation of intratumoral EGF protein and mRNA expression as well as EGFR expression in addition to suppression of immunostaining for the endothelial marker, CD31. iv) SIGNIFICANCE: Taken together, the present results demonstrated that leflunomide possessed anti-angiogenic and anti-proliferative activity against EAC solid tumors that might be correlated to down regulation of EGF and EGFR. Further, the current data indicated that leflunomide may have utility in the management of human cancer.

Effect of Sobatum on tumour development and chemically induced carcinogenesis.

The partially purified component of Solanum trilobatum named Sobatum was obtained from the petroleum ether/ethyl acetate (75:25) extractable portion. It was found to be cytotoxic in Dalton's Lymphoma ascites (DLA), Ehrlich ascites (EA) cell lines and tissue culture cells (L929 and Vero). Sobatum significantly inhibited peritoneal tumours induced by DLA and EA tumour cells. Sobatum was also found to reduce solid tumour growth in mice, when given either simultaneously or prophylactically, and is more active in simultaneous administration (EA). It was found that Sobatum was more active against EA cells-induced solid tumour than DLA-induced solid tumours. On exposure to 7,12-dimethylbenz(a)anthracene (DMBA), about 85.67% animals had induced skin carcinogenesis, which was significantly inhibited to 44.4% by the application of Sobatum. It can be concluded that the Sobatum has the ability to retard the development of solid tumours and DMBA-induced carcinogenesis.

Black tea protects immunocytes from tumor-induced apoptosis by changing Bcl-2/Bax ratio.

It is known that cancer is associated with altered immune function. We demonstrated earlier that black tea inhibits tumor growth in a dose-dependent manner. Here, we report that apoptosis was the cause of immunocyte death in Ehrlich's ascites carcinoma (EAC)-bearing mice and anti-tumor dose of black tea restored EAC-induced immunosuppression by inhibiting apoptosis. A search for the molecular mechanism revealed that EAC burden increased the expression of the pro-apoptotic proteins p53 and Bax in splenic lymphocytes although did not change the level of pro-proliferative protein Bcl-2. Interestingly, anti-tumor dose of black tea down-regulated p53, decreased Bax while augmenting Bcl-2 in these cells. As a result, Bcl-2/Bax ratio was increased and the immunocytes were protected from tumor-induced apoptosis. Thus, unlike many other anti-cancer agents, black tea is not only devoid of immunosuppressive effect but also acts as immuno-restorer in tumor-bearing host. These results, thus, raise the possibility of inclusion of black tea in successful therapeutic regimen against cancer.

Effect of dihydrokainate on the antitumor activity of doxorubicin.

For biochemical modulation, components of green tea have been shown to be useful modulators in combination with doxorubicin (DOX). We have confirmed that theanine enhances the antitumor activity of DOX due to inhibition of DOX efflux from tumor cells. Because theanine is a glutamate analogue, we found that it is associated with a change in the drug transport system on the tumor cell membrane, in particular glutamate transporters. We examined the effect of dihydrokainate (DHK), one of the useful glutamate transporter inhibitors. DHK also inhibits DOX efflux significantly and reduces the glutamate uptake by Ehrlich ascites carcinoma cells. The potential contribution of glutamate transporters not only to glutamate uptake but also to cell membrane export of DOX has been shown. In addition, the combination of DHK with DOX significantly enhances the antitumor activity of DOX, by 1.8-fold (P<0.001). The DOX concentration in tumors significantly increases on combination with DHK and is correlated with the reduced tumor weight. On the other hand, DHK tends to reduce the DOX concentration in normal tissues. We expect that DHK has different actions in tumor and normal tissues because different isoforms of glutamate transporters are expressed in the two tissues. Thus, the results suggest that DHK is a novel and useful modulator for inducing enhancement of antitumor activity.

Protective role of Egyptian propolis against tumor in mice.

BACKGROUND: Propolis has numerous biologic activities including antibiotic, antifungal, antiviral and anti-inflammatory properties. The present work is aimed to study the effect of crude Egyptian propolis on tumor in mice induced by Ehrlich ascitis carcinoma (EAC) cell line. RESULTS: The administration of propolis (160 mg/kg body weight), by gastric intubation 2 h before the intraperitoneal injection of EAC, effectively inhibited tumor growth and the proliferation of EAC. The tumor volume was markedly reduced from 7+/-0.9 ml in EAC-infected mice to 1.6+/-0.95 ml in propolis-treated mice. Also, the lipid peroxide level which was 13.3+/-1.24 nmol malodialdehyde (MDA)/mg protein in EAC infected mice was significantly decreased to 3.3+/-2.1 nmol MDA/mg protein. Reduced glutathione (GSH) and glutathione S-transferase (GST) concentrations were markedly increased in propolis-treated mice. This effect was associated with inhibition of cell cycle progression and induction of apoptosis. Administration of propolis 2 h before injection of EAC arrested cells in G0/G1 phase and resulted in a decrease in the viability, DNA, total RNA and protein level of tumor cells. CONCLUSIONS: Crude Egyptian propolis has a strong inhibitory activity against tumors. The anti-tumor mechanism may be mediated by preventing oxidative damage and induction of apoptosis.

Neem (Azadirachta indica) leaf mediated immune activation causes prophylactic growth inhibition of murine Ehrlich carcinoma and B16 melanoma.

Conditional growth inhibition of murine Ehrlich carcinoma (EC) and B16 melanoma (B16Mel) was observed, following treatment of mice (Swiss and C57BL/6) with aqueous extract of neem (Azadirachta indica) (1 unit/mice/week for 4 weeks) either before or after inoculation of 1 x 10(6) tumor cells. Tumor inoculation after weekly injections for 4 weeks with neem leaf preparation (NLP) induced significant reduction of tumor growth (both EC and B16Mel) and increased survivability of mice. On the other hand, NLP treatment after tumor inoculation demonstrated no tumor growth inhibition in the NLP treated group in comparison to the PBS treated control. No direct cytotoxic effect of NLP towards EC and B16Mel tumor cells was observed in vitro. The spleen cells of NLP treated mice when mixed with inoculum of B16Mel tumor cells and injected into a group of mice, tumor growth was found to be significantly reduced and survivability of the tumor hosts increased remarkably in comparison to mice inoculated with tumor along with normal spleen cells. Concanavalin A (ConA) induced proliferation of lymphocytes from NLP treated mice was significantly higher than the lymphocytes of untreated mice. In in vitro, NLP by itself had no proliferative effects on lymphocytes but it co-stimulated ConA induced mitogenesis. NLP induced lymphocytosis as evidenced by increased lymphocyte count in blood as well as spleen. Flow cytometric evidence suggested that increase in CD4+ and CD8+ T cells accounted for lymphocytosis. The conditional tumor growth retardation, observed in mice treated with NLP before tumor inoculation, may be regulated by NLP mediated immune activation, having prominent role in the cellular immune function of the tumor host.

Effect of haloperidol on the development of the solid Ehrlich tumor in mice.

We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol (s.c) on the development of the Ehrlich solid carcinoma, after inoculation of 1.5 x 10(6) Ehrlich ascites tumor cells into the left footpad of mice. The footpad thickness of haloperidol treated animals was significantly smaller than control from day two after tumor inoculation, to the end of the experiment. Histopathological examination showed that haloperidol treated mice apparently presented less necrotic areas within the tumor mass as well as less invasion of subepithelial connective tissue and other adjacent structures. In particular, in comparison with the control group, no nerve bundles were invaded by neoplastic cells in experimental mice. The possible mechanism underlying these results is discussed in light of the specific pharmacological properties of this neuroleptics drug.

Studies on the endotoxin induced tumor resistance.

In summary, this report has discussed the immunologic mechanisms involved in the enhancement of nonspecific resistance to tumor by endotoxin. The optimal conditions for tumor protection involved pretreatment with approximately 25 mug LPS administered at the siteof subsequent tumor challenge. In an attempt to relate endotoxin structural components to the ability to enhance TUR, a variety of whole LPS's, endotoxic glycolipids and PS preparations were compared. While all of the intact LPS's and several of the glycolipids were effective in enhancing TUR, some endotoxic glycolipids were totally inactive although they were equally toxic. Some lipid-free PS preparations were also active although less than whole LPS. Evidence was presented to suggest that mechanism for enhancement of TUR involves B cells and macrophages but not T cells. The mechanism also involves the production of soluble factors which are released into the serum of mice in response to LPS or PS. These factors can transfer and mediate the antitumor effects of LPS. The preinfection of mice with BCG enhanced the activity of LPS and PS in the production of antitumor activity.