ABSTRACT
PURPOSE: Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. BNCT has been proposed for the treatment of multiple, non-resectable, diffuse tumors in lung. The aim of the present study was to evaluate the therapeutic efficacy and toxicity of BNCT in an experimental model of lung metastases of colon carcinoma in BDIX rats and perform complementary survival studies. MATERIALS AND METHODS: We evaluated tumor control and toxicity in lung 2 weeks post-BNCT at 2 dose levels, including 5 experimental groups per dose level: T0 (euthanized pre-treatment), Boronophenylalanine-BNCT (BPA-BNCT), BPA + Sodium decahydrodecaborate-BNCT ((BPA + GB-10)-BNCT), Beam only (BO) and Sham (no treatment, same manipulation). Tumor response was assessed employing macroscopic and microscopic end-points. An additional experiment was performed to evaluate survival and oxygen saturation in blood. RESULTS AND CONCLUSIONS: No dose-limiting signs of short/medium-term toxicity were observed in lung. All end-points revealed statistically significant BNCT-induced tumor control vs Sham at both dose levels. The survival experiment showed a statistically significant 45% increase in post-treatment survival time in the BNCT group (48 days) versus Sham (33 days). These data consistently revealed growth suppression of lung metastases by BNCT with no manifest lung toxicity. Highlights Boron Neutron Capture Therapy suppresses growth of experimental lung metastases No BNCT-induced short/medium-term toxicity in lung is associated with tumor control Boron Neutron Capture Therapy increased post-treatment survival time by 45.
Subject(s)
Boron Neutron Capture Therapy , Lung Neoplasms/radiotherapy , Translational Research, Biomedical , Animals , Boron Neutron Capture Therapy/adverse effects , Cell Line, Tumor , Colonic Neoplasms/secondary , Dose-Response Relationship, Radiation , Lung Neoplasms/pathology , Radiometry , Rats , Survival AnalysisABSTRACT
PURPOSE: Soy and its fermented products are considered functional foods. The study objective was to assess three functional food - a non-fermented soy product (NFP), fermented soy product (FSP), fermented soy product enriched with isoflavones (FI) - in terms of their ability to reduce the development of adenocarcinoma in mice, as well their ability on modulating immune system. METHODS: It was observed tumor volume and to verify correlations with the immune system it was measured levels of the cytokines IL-1ß and TNF-α produced by macrophages as well as IFN-γ produced by lymphocytes using ELISA test, and nitric oxide production by macrophages using Griess reagent. RESULTS: All products showed immunological activity, but FSP showed the most effective tumor containment, resulting in smallest tumor volumes. FI animals expressed larger amounts of nitric oxide and IL-1ß and exhibited larger tumor sizes than FSP and NFP animals. CONCLUSIONS: The results suggested that the ingestion of FSP was most efficient in tumor containment, possibly due to a positive modulation of the immune system by when Enterococcus faecium and Lactobacillus helveticus are added to the soy product.
Subject(s)
Adenocarcinoma/diet therapy , Antineoplastic Agents/pharmacology , Breast Neoplasms/diet therapy , Enterococcus faecium , Glycine max/microbiology , Lactobacillus helveticus , Adenocarcinoma/immunology , Adenocarcinoma/metabolism , Animals , Breast Neoplasms/immunology , Breast Neoplasms/metabolism , Female , Fermentation , Interferon-gamma/metabolism , Interleukin-1beta/metabolism , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: Ribosome-inactivating proteins (RIP) have been studied in the search for toxins that could be used as immunotoxins for cancer treatment. Pulchellin, a type 2 RIP, is suggested to induce immune responses that have a role in controlling cancer. METHODS: The percentage of dendritic cells and CD4(+) and CD8(+) T cells in the spleen (flow cytometry), cytokines' release by PECs and splenocytes (ELISA) and nitric oxide production by PECs (Griess assay) were determined from tumor-bearing mice injected intratumorally with 0.1 ml of pulchellin at 0.75 µg/kg of body weight. Statistical analysis was performed by one-way ANOVA with Tukey's post hoc test. RESULTS: Pulchellin-treated mice showed significant immune system activation, characterized by increased release of IFN-γ and Th2 cytokines (IL-4 and IL-10), while IL-6 and TGF-ß levels were decreased. There was also an increase in macrophage's activation, as denoted by the higher percentage of macrophages expressing adhesion and costimulatory molecules (CD54 and CD80, respectively). CONCLUSIONS: Our results suggest that pulchellin is promising as an adjuvant in breast cancer treatment.
