Exploring Oral Function, Protein Intake, and Risk of Sarcopenia: A Scoping Review.

INTRODUCTION: Sarcopenia is loss of both muscle mass and function with age and is associated with inadequate protein intake. However, evidence to suggest an association with oral health is less clear. OBJECTIVE: To scope peer-reviewed published evidence (2000-2022) pertaining to oral function in relation to sarcopenia and/or protein intake in older people. METHODS: CINAHL, Embase, PubMed, and Scopus were searched. Included were peer-reviewed studies measuring oral function (e.g., tooth loss, salivary flow masticatory function, strength of muscles of mastication, and tongue pressure) and a measure of protein intake and/or a measure of sarcopenia (appendicular muscle mass and function). Full article screening was conducted by 1 reviewer with a random 10% screened in duplicate by a second reviewer. Relevant content pertaining to study type, country of origin, measures of exposure, and outcomes and key findings was mapped and the balance of data showing a positive versus null association of oral health with outcomes charted. RESULTS: Of 376 studies identified, 126 were screened in full, yielding 32 included texts, of which 29 were original articles. Seven reported intake of protein and 22 reported measures of sarcopenia. Nine distinct oral health exposures were identified, with ≤4 studies relating to any one of these measures. Most data were cross-sectional in nature (27 studies) and from Japan (20 studies). The balance of data showed associations between tooth loss and measures of sarcopenia and protein intake. However, the balance of data pertaining to any association between chewing function, tongue pressure, or indices of oral hypofunction and sarcopenia was mixed. CONCLUSION: A broad range of oral health measures have been studied in relation to sarcopenia. The balance of data suggests that tooth loss is associated with risk, but data pertaining to the oral musculature and indices of oral hypofunction are mixed. KNOWLEDGE TRANSFER STATEMENT: The findings of this research will increase awareness among clinicians of the amount and nature of evidence pertaining to the relationship between oral health and risk of compromised muscle mass and function, including data showing that loss of teeth is associated with increased risk of sarcopenia in older people. The findings highlight to researchers the gaps in the evidence and where further research and clarification of the relationship between oral health and risk of sarcopenia is warranted.

CBP/catenin antagonist safely eliminates drug-resistant leukemia-initiating cells.

CREB-binding protein (CBP) and p300 are highly homologous transcriptional coactivators with unique, non-redundant roles that bind a wide array of proteins, including catenins-ß and γ. ICG-001 is a small-molecule inhibitor that specifically inhibits the CBP/catenin interaction. Importantly, ICG-001 does not inhibit the p300/catenin interaction. We demonstrate that specifically inhibiting the interaction between CBP and catenin with ICG-001 results in the differentiation of quiescent drug-resistant chronic myelogenous leukemia-initiating cells (CML LICs), thereby sensitizing them to BCR-ABL tyrosine kinase inhibitors, for example, Imatinib. Using ICG-001 in a NOD/SCID/IL2Rγ(-/-) mouse model of engrafted human chronic myelogenous leukemia, we now demonstrate the complete elimination of engrafted leukemia after only one course of combined chemotherapy. Combination-treated animals live as long as their non-engrafted littermates. Results from these studies demonstrate that specifically antagonizing the CBP/catenin interaction with ICG-001 can eliminate drug-resistant CML LICs without deleterious effects to the normal endogenous hematopoietic stem cell population.

Pharmacogenetic profiling of CD133 is associated with response rate (RR) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), treated with bevacizumab-based chemotherapy.

Recent studies suggest CD133, a surface protein widely used for isolation of colon cancer stem cells, to be associated with tumor angiogenesis and recurrence. We hypothesized that gene expression levels and germline variations in CD133 will predict clinical outcome in patients with metastatic colorectal cancer (mCRC), treated in first-line setting with 5-fluorouracil, oxaliplatin and bevacizumab (BV), and we investigated whether there is a correlation with gene expression levels of CD133, vascular endothelial growth factor (VEGF) and its receptors. We evaluated intra-tumoral gene expression levels by quantitative real-time (RT) PCR from 54 patients and three germline variants of the CD133 gene by PCR-restriction-fragment length polymorphism from 91 patients with genomic DNA. High gene expression levels of CD133 (>7.76) conferred a significantly greater tumor response (RR=86%) than patients with low expression levels (7.76, RR=38%, adjusted P=0.003), independent of VEGF or its receptor gene expression levels. Gene expression levels of CD133 were significantly associated with VEGF and its receptors messenger RNA levels (VEGFR-1 (P<0.01), -2 and -3, P<0.05). Combined analyses of two polymorphisms showed a significant association with progression-free survival (PFS) (18.5 months vs 9.8 months, P=0.004) in a multivariate analysis as an independent prognostic factor for PFS (adjusted P=0.002). These results suggest that CD133 is a predictive marker for standard first-line BV-based treatment in mCRC.