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The genetic alteration of colorectal cancer cell lines

The activity of cell surface EGFR and total EGFR.

The relationship between EGFR downregulation and early tumor shrinkage

The colorectal cancer cell lines and their culture conditions

The relative amount of EGFR labeled with cetuximab.

Chronological changes in the number of EGFRs on the cell surface.

Supplementary Table 3 from Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

Supplementary Table 1 from Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

Supplementary Table 2 from Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

CCR Translation for This Article from Randomized Double-Blind Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and to Prevent Sporadic Colorectal Polyps

Purpose: On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer.Experimental design: Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted.Results: ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed.Conclusions: ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer. Clin Cancer Res; 17(11); 3803–11. ©2011 AACR.

Purpose: On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer. Experimental design: Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted. Results: ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed. Conclusions: ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer. Clin Cancer Res; 17(11); 3803–11. ©2011 AACR.

The number of overweight and obese individuals continues to increase in both the U.S. and worldwide. This increase has led to a significant increase in obesity-related medical problems including diabetes mellitus, cardiovascular disease and cancer. In obesity, the differentiation of adipocytes is suppressed. Although adipocyte differentiation is associated with changes in glucose metabolism, little is known about the potential of enzymes involved in glucose metabolism to modulate this process. Pyruvate kinase (PK) mediates the rate-limiting step of glycolysis. The M2 isoform of PK (PKM2) is expressed in adipocytes but its role in adipogenesis is unknown. Here we demonstrate that PKM2 regulates the differentiation of both human and mouse adipocytes. Silencing of PKM2 in preadipocytes led to increased lipid accumulation, enhanced expression of markers (FABP4, PPARgamma, C/EBPBeta) of adipocyte differentiation and caused a shift in the pattern of enzymes involved in glucose metabolism favoring the TCA cycle. Overexpression of PKM2 suppressed adipocyte differentiation. In obesity, increased numbers of macrophages are found in adipose tissue and are believed to contribute to insulin resistance. Interestingly, we found that activated macrophages produce factors that inhibit adipocyte differentiation leading to increased levels of enzymes involved in aerobic glycolysis including PKM2. Given its importance in regulating adipocyte differentiation, we investigated the mechanism by which PKM2 expression was regulated. The HIF-1alpha - c-Myc - HnRNPA1 pathway induced PKM2 in preadipocytes. The redox sensor CtBP1 was found to be a negative regulator of this pathway. Taken together, these results provide evidence that PKM2 is not only expressed in adipose tissue but is also a determinant of adipocyte differentiation. Whether pharmacologically targeting PKM2 will impact on obesity or its consequences warrants further investigation. Citation Format: Tetsuo Kimura, Priya Bhardwaj, Domenick J. Falcone, Andrew J. Dannenberg, Kotha Subbaramaiah. Pyruvate kinase M2 regulates adipocyte differentiation and the expression of enzymes involved in glucose metabolism. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B36.