Establishment of linear accelerator-based image guided radiotherapy for orthotopic 4T1 mouse mammary tumor model / 한국실험동물학회지

This study was conducted to assess the feasibility of image guided radiotherapy (IGRT) for orthotopic 4T1 mouse mammary tumor using linear accelerator (LINAC). Eighteen Balb/C mice were inoculated with 4T1 cells on left mammary fat pad and nine of them were irradiated using LINAC. Tumors, planning target volumes (PTV), bowels adjacent to tumors, bones and lungs were delineated on planning CT images. IGRT plans were generated to irradiate prescription dose to at least 90% of the PTV and then compared with conventional 2-dimensional plans with anterior-posterior and posterior-anterior beams with 5 mm margins (2D AP/PA plan). Homemade dose-build-up-cradle was designed to encompass mouse bed for homogeneous dose build up. To confirm the irradiated dose, tumor doses were measured using diode detector placed on the surface of tumors. Plan comparison demonstrated equivalent doses to PTV while sparing more doses to normal tissues including bowel (from 90.9% to 40.5%, median value of mean doses) and bone marrow (from 12.9% to 4.7%, median value of mean doses) than 2D AP/PA plan. Quality assurance using diode detector confirmed that IGRT could deliver 95.3-105.3% of the planned doses to PTV. Tumors grew 505.2-1185.8% (mean 873.3%) in the control group and 436.1-771.8% (mean 615.5%) in the irradiated group. These results demonstrate that LINAC-based IGRT provides a reliable approach with accurate dose delivery in the radiobiological study for orthotropic tumor model maintaining tumor microenvironment.

Targeting the Transforming Growth Factor-beta Signaling in Cancer Therapy

TGF-beta pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-beta (TGF-beta) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-beta related functional contexts. This review discusses the molecular mechanism of the TGF-beta pathway and describes the different ways of tumor suppression and promotion by TGF-beta. In the last part of the review, the data on targeting TGF-beta pathway for cancer treatment is assessed. The TGF-beta inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

Inhibitor of DNA-binding 4 contributes to the maintenance and expansion of cancer stem cells in 4T1 mouse mammary cancer cell line / 한국실험동물학회지

The cancer stem cell (CSC) hypothesis proposes that CSCs are the root of cancer. CSC-targeted therapies may prevent cancer relapse and provide more effective treatment. The expression of aldehyde dehydrogenase 1, as assessed by the Aldefluor assay, has been recognized as a marker of CSCs in breast cancer. Inhibitors of DNA-binding proteins (IDs) have an important role in stem cell differentiation. In this study, we examined IDs necessary for the regulation of stem properties in Aldefluorpos 4T1 cells. When the expression profile of IDs in Aldefluorneg and Aldefluorpos 4T1 cells was compared, qRT-PCR analysis showed that ID4 expression was highly upregulated in Aldefluorpos 4T1 cells. In addition, knockdown of ID4 expression suppressed the properties of CSCs, including their sphere-forming ability and side population phenotype. The findings suggest that ID4 may be a therapeutic target for the treatment of advanced breast cancer.

OCT4 Expression Enhances Features of Cancer Stem Cells in a Mouse Model of Breast Cancer / 한국실험동물학회지

The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for metastasis and disease recurrence. Therefore, targeting CSCs has the potential to significantly improve outcomes for cancer patients. The OCT4 transcription factor gene is a master gene that plays a key role in the self-renewal and pluripotency of stem cells. In this study, we introduced an OCT4 reporting vector into 4T1 mouse breast cancer cells and sorted OCT4 high and OCT4 low cell populations. We then determined whether OCT4 expression is associated with maintenance and expansion of CSCs. We found that OCT4high 4T1 cells have an increased ability to form tumorsphere and a high expression of stem cell markers such as Sca-1, CD133, CD34, and ALDH1, when compared with OCT4low 4T1 cells. In addition, OCT4high 4T1 cells have greater tumorigenic potential in vivo. These findings suggest that OCT4 expression may be a useful target for stem cell-specific cancer therapy.

Anti-inflammatory Effect of Quercetin on Picryl Chloride-induced Contact Dermatitis in BALB/c Mice / 한국실험동물학회지

In this study, we investigated that anti-inflammatory effect of quercetin on picryl chloride(PCL)-induced contact dermatitis in BALB/c Mice. Experimental animals were divided into three groups and comprising five animals. All groups of oral administration was begun on the first day of PCL treatment and ceased on day 5. For the induction of contact dermatitis, BALB/c mice were sensitized with 40 microliter of 1.5% picryl choloride (PCL) to the left and right ear, respectively. Ear swelling responses were much weaker in high-dose group (100 mg/kg) than control group (0 mg/kg). Total serum IgE levels and histamine levels were measured by sandwich ELISA method using mouse IgE, histamine measuring Kit. Both total serum IgE and histamine levels were significantly decreased in high-dose group (100 mg/kg) than other groups. Degranulation of mast cells were also confirmed by Toluidine Blue (TB) staining method. In high-dose group (100 mg/kg), the number of mast cells were significantly decreased and there are many mast cells were shown degranulation in control group (0 mg/kg). All of these results demonstrate that the pharmacological actions of quercetin indicate their potential activity for allergic inflammatory diseases through the down-regulation of mast cell activation.