Background: Breast cancer is the most common cancer in women worldwide and is the leading cause of death amongst women with cancer. One novel therapy used for breast cancer treatment constitutes non-contact electric fields and is called electro-capacitive cancer therapy (ECCT) with intermediate frequency and low intensity. The objective of this study was to examine the effect of ECCT on mammary tumors growth in rats and observing the immune responses that play a role in fighting the tumor. Methods: Female SD rats were used and divided into four groups, namely control (NINT), placebo (NIT), non- therapy (INT), and therapy (IT) groups with 6 biological replicates in each group. Rats in INT and IT groups were treated with 7,12-dimethylbenz[a]anthracene for mammary tumor induction. Only rats in NIT and IT groups were exposed to ECCT individually for 10 hours per day for 21 days. The size of all tumors was measured with a digital caliper. The distributions of PCNA, ErbB2, caspase-3, CD68, CD4, and CD8-positive cells were observed with immunohistochemistry and scoring with ImageJ. Results: The growth rate of mammary tumors in IT group was significantly lower (p<0.05) than that in INT group. The number of mitotic figures and the percentage of PCNA, caspase-3, and CD68-positive cells in IT group were significantly lower (p<0.05) than those in INT group. Conversely, the percentage of CD8-positive T cells in IT group was significantly higher (p<0.05) than that in INT group. Moreover, the CD4/CD8 ratio in IT group was found to have decreased. Some tumor tissues were blackened and detached from the surrounding tissue, resulting in an open wound which then healed upon exposure. Conclusions: Non-contact electric fields exposure showed inhibition on mammary tumor growth in rats while inducing CD8+ T cells, leading to tumor cell death and potentially helping wounds heal.
Background: Breast cancer is the most common cancer in women worldwide and is the leading cause of death in women with cancer. One novel therapy used for breast cancer treatment is non-contact electric fields called electro-capacitive cancer therapy (ECCT) with intermediate frequency (100 kHz) and low intensity (18 Vpp). The objective of this study was to examine the effect of ECCT on mammary tumors growth in rats and observing the immune responses that play a role in fighting the tumor. Methods: Female SD rats were used and divided into four groups, namely control (NINT), placebo (NIT), non- therapy (INT), and therapy (IT) groups with 6 biological replicates in each group. Rats in INT and IT groups were treated with 7,12-dimethylbenz[a]anthracene for mammary tumor induction. Only rats in NIT and IT groups were exposed to ECCT individually for 10 hours per day for 21 days. The size of all tumors was measured with a digital caliper. The distributions of PCNA, ErbB2, caspase-3, CD68, CD4 and CD8-positive cells were observed with immunohistochemistry and scoring with ImageJ. Results: The growth rate of mammary tumors in IT group was significantly lower (p<0.05) than that in the INT group. The number of mitotic figures and the percentage of PCNA, caspase-3, and CD68- positive cells in IT group were significantly lower (p<0.05) than those in INT group. Conversely, the percentage of CD8-positive T cells in IT group was significantly higher (p<0.05) than that in INT group. Moreover, the CD4/CD8 ratio in IT group was decreased. Some tumor tissues were blackened and detached from the surrounding tissue, resulting in an open wound which then healed up upon exposure. Conclusions: Non-contact electric fields exposure showed inhibition on mammary tumor growth in rats while inducing CD8+ T cells that lead to tumor cells death and potentially helps wound healing.
Background: There were an estimated 2.1 million breast cancer diagnoses in 2018 worldwide, which is about 11.6% of the total cancer incidence. A novel modality of cancer treatment based on exposure to non-contact electric fields has been developed to reduce cancer incidence. However, the safety of the electric field exposure was not fully investigated. Therefore, the purpose of this study is to observe the safety of the electric field exposure on renal and liver structure. Methods: Female Sprague-Dawley rats were divided into one control group and three treatment groups. Animals were treated with 7,12-dimethylbenz[a]anthracene for mammary tumour induction and exposed to non-contact electric fields individually for 10 hours a day for three weeks. Fresh samples of the kidney and liver were collected for observing structural damage in both organs. The two organs were prepared for histopathological cross-sectioning using the paraffin method and Hematoxylin & Eosin staining followed by histological scoring using the post-examination masking method. Results: The damages found in the kidney were the following: thickening of Bowman capsule, karyolysis, karyorrexhis, pyknosis, cloudy swelling, epithelial sloughing, inflammation, haemorrhage, and congestion. The number of inflammation and haemorrhage in the kidney structure of the placebo group was the lowest and significantly different from the three other groups. All damages in the kidney were also found in the liver, but each showed different levels of damage. The damages in the kidney and liver caused by the exposure were not significant. Conclusions: The non-contact electric fields were not harmful to renal and liver structure in tumour-induced rats. Instead, it may increase the renal function in normal rats.
targeted alpha-particle radiation therapy for LMGC in a preclinical mouse model. Material and methods Astatine-211 (At-211), an alpha-particle emitter radionuclide, was produced by irradiation of alpha-particles to bismuth-209 using an AVF accelerator at our institute. An anti-HER2 antibody trastuzumab was conjugated with At-211 to produce alpha-emitting antibodies targeting HER2 ([At-211]-trastuzumab). To generate a mouse model of LMGC, we injected luciferase-labelled HER2-positive human metastatic NCI-N87 GC cells into splenic vein of severe combined immunodeficiency mouse. Tissue and tumour distribution of [At-211]-trastuzumab was examined in the LMGC mouse model. Therapeutic efficacy and toxicities of [At-211]-trastuzumab were evaluated in the animal model. All animal experiments conducted in this study were approved by the Animal Care and Use Committee of our institute and were undertaken in compliance with the institutional guidelines regarding animal care and handling. Results and discussions Biodistribution studies showed that the maximum uptake of trastuzumab in the liver metastatic tumours was approximately 12% of injected dose per tissue gram at 24 hours after injection.A systemic injection of [At-211]trastuzumab (1 MBq) significantly reduced a tumour burden in the liver and extended the survival of model mouse. Transient leukocytopenia was observed in mice received 1 MBq of [At-211]trastuzumab at 5-7 days after injection. No body weight loss was so far found in the mice treated with [At-211]trastuzumab. Conclusion Our preclinical study provides the evidence that targeted alpha-therapy using [At-211]-trastuzumab is effective for LMGC.
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