Localization of active, dually phosphorylated extracellular signal-regulated kinase 1 and 2 in colorectal cancer with or without activating BRAF and KRAS mutations

SummaryColorectal cancers (CRC) often show activating mutations of the KRAS or BRAF genes, which stimulate the extracellular signal-regulated kinase (ERK) pathway, thus increasing cell proliferation and inhibiting apoptosis. However, immunohistochemical results on ERK activation in such tumors differ greatly. Recently, using a highly optimized immunohistochemical method, we obtained evidence that high levels of ERK activation in rectal adenocarcinomas were associated with resistance to radiochemotherapy. In order to determine whether KRAS and/or BRAF mutations correlate to immunohistochemically detectable increases in phosphorylation of ERK (pERK), we stained biopsies from 36 CRC patients with activating mutations in the BRAF gene (BRAFV600E: BRAFm), the KRAS gene (KRASm) or in neither (BRAF/KRASn) with this optimized method. Staining was scored in blind-coded specimens by two observers. Staining of stromal cells was used as a positive control. BRAFm or KRASm tumors did not show higher staining scores than BRAF/KRASn tumors. Although BRAFV600E staining occurred in over 90% of cancer cells in all 9 BRAFm tumors, 3 only showed staining for pERK in less than 10% of cancer cell nuclei. The same applied to 4 of the 14 KRASm tumors. A phophorylation-insensitive antibody demonstrated that lack of pERK staining did not reflect defect expression of ERK1/2 protein. Thus, increased staining for pERK does not correlate to BRAF or KRAS mutations even with a highly optimized procedure. Further studies are required to determine whether this reflects differences in expression of counterregulatory molecules, including ERK phosphatases

Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

Objective To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation

A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults

\ua9 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres

Endoscopic ultrasonography guided fine needle aspiration biopsy for staging malignant melanoma of the esophagus: A case report

BACKGROUND: Malignant melanoma (MM) rarely involves the esophagus. The outlook is dismal unless lesional tissue is limited to the esophageal wall. Hence, staging prior to extensive surgical intervention is desirable. CASE: A 54-year-old male presented with fatigue and melena. A diagnosis of MM primary in the esophagus was rendered on a biopsy of an esophageal polyp. The stage, determined by endoscopic ultrasonography-guided fine needle aspiration biopsy, was advanced. On the basis of this information, it was decided to spare the patient mutilating surgery. CONCLUSION: This report confirms the utility of endoscopic ultrasonography-guided fine needle aspiration biopsy in documenting the extent of lesions at sites difficult to access. Thus, management can be improved