Low-grade slightly elevated and polypoid colorectal adenomas display differential β-catenin-TCF/LEF activity, c-Myc, and cyclin D1 expression

AIM To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas.METHODS Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. five commonly mutated genes(APC, BRAf, KRAS, NRAS, and PIK3CA) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index(AI) and Ki-67 labeling index(KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. western blots, luciferase assays for β-catenin-T-cell factor protein/β-cateninlymphoid enhancer factor(β-catenin-TCf/LEf)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines.RESULTS Slightly elevated lesions showed a significantly lower APC mutational frequency and a significantly higher KRAS mutational frequency(both P < 0.05). Slightly elevated lesions showed a significantly lower AI(P < 0.05). β-catenin and β-catenin-TCf/LEf-driven transcriptional activity was significantly upregulated in slightly elevated lesions(both P < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated(both P < 0.05). β-catenin-TCf/LEf-driven transcriptional activity was negatively correlated with c-Myc(ρ =-0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-x L upregulation(both P < 0.05) along with significant decreases in caspase-9 and caspase-3 activity(both P < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-x L(ρ =-0.74 and-0.78, respectively).CONCLUSION The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.

Restricting carbohydrates to fight head and neck cancer——is this realistic?

Head and neck cancers(HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates(CHOs) and their replacement with fat, mostly in form of a ketogenic diet(KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are(1) targeting the origin and specific aspects of tumor glycolysis;(2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill;(3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.