RESUMEN
Pectin constitutes an essential component of dietary fiber. Modified pectins from various sources possess potent anticancer and immunomodulatory activities. In this study, two pectins isolated from apple pomace by Trichoderma enzyme treatment, PX (with endo-xylanase) and PCX (with both endo-cellulase and endo-xylanase), were studied in colon cancer cell lines (HCT 116, Caco-2, and HT-29). Both pectins reduced colon cancer cell viability, induced apoptosis, and increased intracellular amounts of reactive oxygen species. Additionally, synergy between pectin and an active form of irinotecan, SN-38, in all aspects mentioned above, was discovered. This drug is a common component of cytotoxic combinations recommended as treatment for colon cancer patients. PX and PCX demonstrated significant anti-inflammatory activity in lipopolysaccharide-stimulated cells. Interaction of apple pectins with galectin-3 and Toll-like Receptor 4 (TLR4) was suggested to be responsible for their anticancer and anti-inflammatory effect. Since PCX was more active than PX in almost all experiments, the role of the enzyme used to obtain the pectin for its biological activity was discussed. It was concluded that co-operation between both enzymes was needed to obtain the molecule of the most beneficial properties. The low molecular mass of PCX together with a high proportion of rhamnogalacturonan I (RG I) regions seemed to be crucial for its superior activity.
RESUMEN
Colorectal cancer (CRC) is the second cause of cancer death worldwide. The composition and enzymatic activity of colonic microbiota can significantly affect the effectiveness of CRC chemotherapy. Irinotecan is a drug widely used to treat colon cancer. However, the transformation of a drug-glucuronide (SN-38G) back to its active form (SN-38) by bacterial ß-glucuronidase (GUS) constitutes the primary reason for the observed intestinal toxicity of irinotecan. It was demonstrated that novel enzymatically extracted apple pectin (PC) might be a promising candidate for an adjunct to irinotecan therapy. PC itself reduced the viability of HCT 116 and Caco-2 colorectal cancer cells, induced apoptosis, and increased intracellular reactive oxygen species production. Moreover, PC enhanced the cytotoxic and proapoptotic effect of irinotecan (at concentrations below its IC50), i.e., synergistic effect was recorded. Additionally, PC exhibited potent anti-inflammatory properties and prevented adhesion of prototype adherent-invasive E. coli (AIEC) LF82 strain and laboratory K-12C600 strain to colon cancer cells. PC was also identified to be an effective inhibitor of bacterial GUS activity. Altogether, novel apple pectin was identified as a promising candidate for a supplement to irinotecan therapy that might alleviate its side-effects via inhibition of bacterial GUS and thus increasing its therapeutic efficacy.
RESUMEN
BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) is increasing; however, it is not clear whether this reflects an increase in the incidence of incidental or in that of non-incidentally (presurgically) discovered PTMC (IPTMC vs. NIPTMC). We assessed the incidence of IPTMC and NIPTMC over the past 9 years, to discern whether the increase in PTMC incidence is due to improved diagnostics or to a real increase in the incidence. METHODS: We performed a retrospective chart review of 4327 patients who were consecutively admitted to and surgically treated for thyroid pathology at a single institution. As a main presurgical diagnostic test, all patients underwent ultrasound-guided fine-needle aspiration biopsy (UG-FNAB). The analyzed time frame was divided into three equal periods (I: 2008-2010, II: 2011-2013, III: 2014-2016), and IPTMCs and NIPTMCs were assessed and compared in each period. RESULTS: We evaluated 393 (9.08%) patients with thyroid malignancy, of which 156 (3.60% of all thyroid tumors [TTs]; 39.69% of all thyroid cancers [TCs]) were diagnosed as PTMC. The prevalence of NIPTMC among all TCs increased from 16.66% in 2008 to 33.75% in 2016, while that of IPTMC decreased from 20.83% in 2008 to 13.75% in 2016. The incidence rates of NIPTMC and IPTMC in period III differed statistically significantly (p < 0.0001). The prevalence rate of NIPTMC in period III was higher than that in period II, yet comparable to that in period I (p = 0.0014; p = 0.2804, respectively). CONCLUSIONS: The prevalence of NIPTMC, rather than that of IPTMC, is escalating; this may be due to better presurgical diagnosis.
