Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

ABSTRACT: BACKGROUND: Skeletal uptake of 99mTc labelled methylene diphosphonate (99mTc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99mTc-MDP. METHODS: 22 postmenopausal women (52-80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99mTc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). RESULTS: The median TSU of 99mTc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. CONCLUSION: In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99mTc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption

Biomarkers and signaling pathways of colorectal cancer stem cells

The progression of colorectal cancer is commonly characterized by accumulation of genetic or epigenetic abnormalities, altering regulation of gene expression as well as normal protein structures and functions. Nonetheless, there are some questions that remain to be elucidated, such as the origin of cancer cells and populations of cells initiating and propagating tumor development. Currently, there are two rival theories describing the process of carcinogenesis. One is the stochastic model, arguing that any cell is capable of initiating and triggering the development of cancer. Meanwhile, the cancer stem cell model hypothesizes that only a small fraction of stem cells possesses cancer-promoting properties. Typically, colorectal cancer stem cells (CSCs) share the same molecular signaling profiles with normal stem cells or embryonic stem cells, such as Wnt, Notch, TGF-β, and Hedgehog. Nevertheless, CSCs differ from normal stem cells and the bulk of tumor cells in their tumorigenic potential and susceptibility to chemotherapeutic drugs. This may be a possible explanation of the high percentage of cancer recurrence in patients who underwent chemotherapeutic treatment and surgery. This review article focuses on the colorectal cancer stem cell biomarkers and the role of upregulated signaling pathways implicated in the initiation and progression of colorectal cancer