Gamma-radiated immunosuppressed tumor xenograft mice can be a new ideal model in cancer research.

Tumor xenograft models can create a high capacity to study human tumors and discover efficient therapeutic approaches. Here, we aimed to develop the gamma-radiated immunosuppressed (GIS) mice as a new kind of tumor xenograft model for biomedical studies. First, 144 mice were divided into the control and treated groups exposed by a medical Cobalt-60 apparatus in 3, 4, and 5 Gy based on the system outputs. Then, 144 BALB/c mice were divided into four groups; healthy, xenograft, radiation, and radiation + xenograft groups. The animals in the xenograft and radiation + xenograft groups have subcutaneously received 3 × 106 MCF-7 cells 24 h post-radiation. On 3, 7, 14, and 21 days after cell injection, the animals were sacrificed. Then, the blood samples and the spleen and tumor tissues were removed for the cellular and molecular analyses. The whole-body gamma radiation had a high immunosuppressive effect on the BALB/c mice from 1 to 21 days post-radiation. The macroscopic and histopathological observations have proved that the created clusters' tumor structure resulted in the xenograft breast tumor. There was a significant increase in tumor size after cell injection until the end of the study. Except for Treg, the spleen level of CD4, CD8, CD19, and Ly6G was significantly decreased in Xen + Rad compared to the Xen alone group on 3 and 7 days. Unlike IL-4 and IL-10, the spleen level of TGF-ß, INF-γ, IL-12, and IL-17 was considerably decreased in the Xen + Rad than the Xen alone group on 3 and 7 days. The spleen expressions of the VEGF, Ki67, and Bax/Bcl-2 ratio were dramatically increased in the Xen + Rad group compared to the Xen alone on 3, 7, 14, and 21 days. Our results could confirm a new tumor xenograft model via an efficient immune-suppressive potential of the whole-body gamma radiation in mice.

Evaluation of the treatment strategies on patient-derived xenograft mice of human breast tumor.

Since only a minority of patients may respond to single-agent therapies, methods to test the potential antitumor activity of rational combination therapies are still needed. This study aimed to characterize the efficacy of antitumor combination therapies in vivo within the primary tumor using patient-derived xenograft (PDX) models by gamma-irradiation-induced immune suppression. We employed four Luminal A PDX models obtained from human mammary tumors grown in mice. PDX models were implanted into the right flank of mice, and treatments have ensued once tumor volume reached ~150 mm3. Four of the active drugs- Adriamycin, Cyclophosphamide, Taxotere, and Tamoxifen-were tested in vivo to treat mammary tumors. The tumor volume was measured during the study. The mice's immune system was inherently suppressed by gamma irradiation, thus allowing human tumors to grow. The results showed that the tumorigenesis rate of the PDX model was from 65 to 80%. PDX models were successfully established with a high frequency of tumor engraftment. Humanized mice treated with a two-drug regimen, that is, adriamycin + cyclophosphamide exhibited an increased antitumor response than a three-drug regimen, that is, adriamycin + cyclophosphamide + taxotere that correlated with tumor growth inhibition. Combination therapies with adriamycin + cyclophosphamide in PDX mice reduced tumor growth in four Luminal A PDX models. These preclinical results suggest that a two-drug regimen than a three-drug regimen can be useful for breast cancer patients. This study provides insights for future studies combining chemotherapeutics with targeted therapies using PDX models by gamma-irradiation-induced immune suppression.

Expression Analysis of Previously Verified Fecal and Plasma Dow-regulated MicroRNAs (miR-4478, 1295-3p, 142-3p and 26a-5p), in FFPE Tissue Samples of CRC Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality worldwide. Early diagnosis of this neoplasm is critical and may reduce patients' mortality. MicroRNAs are small non-coding RNA molecules whose expression pattern can be altered in various diseases such as CRC. METHODS: In this study, we evaluated the expression levels of miR-142-3p, miR-26a-5p (their reduced expression in plasma samples of CRC patients was previously confirmed), miR-4478 and miR-1295-3p (their reduced expression in stool samples of CRC patients was previously confirmed) in tissue samples of CRC patients in comparison to healthy subjects. To achieve this purpose, total RNA including small RNA was extracted from 53 CRC and 35 normal subjects' Formalin-fixed, Paraffin-embedded (FFPE) tissue samples using the miRNeasy FFPE Mini Kit. The expression levels of these four selected miRNAs were measured using quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). RESULTS: We found that the expression levels of miR-4478 and miR-1295b-3p (two previously down-regulated fecal miRNAs) were significantly decreased in FFPE samples of CRC patients compared to healthy controls. On the other hand, no significant differences were seen in expression levels of miR-142-3p and miR-26a-5p (two previously down-regulated circulating miRNAs) in FFPE samples between these two groups. CONCLUSION: Regarding current findings, it may be concluded that to diagnose CRC patients based on the miRNAs approach, stool samples are more likely preferable to plasma samples; nevertheless, additional studies with more samples are needed to confirm the results.