Supplementary Material for: Augmented Pentose Phosphate Pathway Plays Critical Roles in Colorectal Carcinomas

Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 μM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP⁺ ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs

Supplementary Material for: The Ameliorating Effect of Lactobacillus gasseri OLL2716 on Functional Dyspepsia in Helicobacter pylori-Uninfected Individuals: A Randomized Controlled Study

<p><b><i>Background/Aims:</i></b> Probiotics appear to improve <i>Helicobacter pylori</i>-associated dyspepsia via an inhibitory effect on <i>H. pylori;</i> however, uncertainty exists regarding their effects in <i>H. pylori</i>-uninfected individuals. We evaluated the efficacy of <i>Lactobacillus gasseri</i> OLL2716 (<i>L. gasseri</i> OLL2716) on <i>H. pylori</i>-uninfected individuals with functional dyspepsia (FD). <b><i>Methods:</i></b> A double-blind, parallel-group, placebo-controlled, randomized, controlled trial was performed. Participants were randomly assigned to ingest <i>L. gasseri</i> OLL2716-containing yogurt (<i>L. gasseri</i> OLL2716 group) or <i>L. gasseri</i> OLL2716-free yogurt (placebo group) for 12 weeks. Participants completed questionnaires that dealt with a global assessment as well as symptom severity. The per-protocol (PP) population was evaluated for efficacy in accordance with a plan prepared beforehand. <b><i>Results:</i></b> Randomization was performed on 116 individuals; the PP population consisted of 106 individuals (mean age 42.8 ± 9.0). The impressions regarding the overall effect on gastric symptoms were more positive in the <i>L. gasseri</i> OLL2716 group compared to that in the placebo group (statistical trend; <i>p</i> = 0.073). The elimination rate for major FD symptoms was 17.3 and 35.3% in the placebo and <i>L. gasseri</i> OLL2716 groups respectively (<i>p</i> = 0.048). <b><i>Conclusion:</i></b><i>L. gasseri</i> OLL2716 has beneficial effects on FD without <i>H. pylori</i> involvement.</p

Supplementary Material for: Analysis of the characteristics of coexisting lesions in colorectal cancer patients in an international study: A subgroup analysis of the ATLAS trial

Introduction: We investigated coexisting lesion types in patients with invasive colorectal cancer (CRC) in a multinational study for comprehending the adenoma-carcinoma and serrated pathway about the development of CRC. Methods: We retrospectively reviewed 3050 patients enrolled in the international randomized controlled trial (ATLAS study) to evaluate the colorectal polyp detection performance of image-enhanced endoscopy in 11 institutions in four Asian countries/regions. In the current study, as a subgroup analysis of the ATLAS study, 92 CRC patients were extracted and compared to 2958 patients without CRC to examine the effects of age, sex, and coexisting lesion types (high-grade adenoma [HGA], low-grade adenoma with villous component [LGAV], 10 adenomas, adenoma ≥10 mm, sessile serrated lesions [SSL], and SSL with dysplasia [SSLD]). Additional analyses of coexisting lesion types were performed according to sex and location of CRC (right- or left-sided). Results: A multivariate analysis showed that HGA (odds ratio [95%confidence interval] 4.29 [2.16-8.18]; p<0.01), LGAV (3.02 [1.16-7.83], p=0.02) and age (1.04 [1.01-1.06], p=0.01) were independently associated with CRC. According to sex, the coexisting lesion types significantly associated with CRC were LGAV (5.58 [1.94-16.0], p<0.01) and HGA (4.46 [1.95-10.20], p<0.01) in males and HGA (4.82 [1.47-15.80], p<0.01) in females. Regarding the location of CRC, SSLD (21.9 [1.31-365.0], p=0.03) was significant for right-sided CRC, and HGA (5.22 [2.39-11.4], p<0.01) and LGAV (3.46 [1.13-10.6], p=0.02) were significant for left-sided CRC. Conclusions: The significant coexisting lesions in CRC differed according to sex and location. These findings may contribute to comprehending the pathogenesis of CRC