ABSTRACT
OBJECTIVE: The aim of this study was to show whether local application of cadmium-impregnated bone cement can induce apoptosis and decrease the viability of residual osteosarcoma (OS) cells in nude mice. METHODS: K7M2 tumorigenic OS cell line was cultivated in vitro. The xenograft tumor model was formed by subcutaneously adding the tumor cells to athymic nude mice. Tumor was formed within 1 month. Then, mice were randomly assigned to five groups, each containing seven nude mice: control (group 1), wide resection (group 2), intralesional resection (group 3), intralesional resection + bone cement (group 4), and intralesional resection + cadmium embedded in bone cement (group 5). Tumor resection with 1 cm surgical margins was performed in the wide resection group. In intralesional resection groups, tumor tissue was resected with positive margins aiming to leave 15 mm3 of macroscopic tumor tissue. In group 3, the defect was left empty; groups 4 and 5 received bone cements prepared with saline and cadmium solutions, respectively. After the resection, mice were observed for 15 days and sacrificed. Next, surgical resection sites were evaluated histopathologically in each group. RESULTS: Recurrent tumor was formed in all mice in the wide resection group, and apparent progression of residual tumor was observed in groups 3 and 4. On the contrary, only a thin layer of residual tumor was observed around the bone cement in group 5. Histological evaluation revealed remarkable necrosis in group 5 and lowest viability compared to other groups. No systemic toxic effect related to cadmium was observed. CONCLUSION: Our data suggest that local application of cadmium in bone cement has a significant potential to increase tumor necrosis and decrease the viability of residual OS cells.
Subject(s)
Apoptosis/drug effects , Bone Cements , Bone Neoplasms , Cadmium/pharmacology , Necrosis/chemically induced , Osteosarcoma , Animals , Bone Cements/chemistry , Bone Cements/pharmacology , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Survival/drug effects , Cells, Cultured , Disease Models, Animal , Humans , Mice , Neoplasm Recurrence, Local/pathology , Osteosarcoma/metabolism , Osteosarcoma/pathology , Xenograft Model Antitumor AssaysABSTRACT
Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages. However, colorectal cancer is not a single type of tumor; its pathogenesis depends on the anatomical location of the tumor and differs between right side and left side of the colon. Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. Therapy responses are totally different between these tumor entities. Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC) patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapies because these tumors have high antigenic load. For the development of effective therapy regimes and better treatment options, it is essential to evaluate right-sided and left-sided tumors as separate entities, and design the therapy regime considering the differences between these tumors.
