Several studies have suggested ERBB3/HER3 may be a useful prognostic marker for colorectal cancer. Tumours with an intestinal stem cell signature have also been shown to be more aggressive. Here, we investigate whether ERBB3 is associated with intestinal stem cell markers in colorectal cancer and if cancer stem cells within tumours are marked by expression of ERBB3. Expression of ERBB3 and intestinal stem cell markers (LGR5, EPHB2, CD44s and CD44v6) was assessed by qRT-PCR in primary colorectal tumours (stages 0 to IV) and matched normal tissues from 53 patients. The localisation of ERBB3, EPHB2 and KI-67 within tumours was investigated using co-immunofluorescence. Expression of ERBB3 and intestinal stem cell markers were significantly elevated in adenomas and colorectal tumours compared to normal tissue. Positive correlations were found between ERBB3 and intestinal stem cell markers. However, co-immunofluorescence analysis showed that ERBB3 and EPHB2 marked specific cell populations that were mutually exclusive within tumours with distinct proliferative potentials, the majority of ERBB3+ve cells being non-proliferative. This pattern resembles cellular organisation within normal colonic epithelium where EPHB2 labelled proliferative cells reside at the crypt base and ERBB3+ve cells mark differentiated cells at the top of crypts. Our results show that ERBB3 and intestinal stem cell markers correlate in colorectal cancers. ERBB3 localises to differentiated cell populations within tumours that are non-proliferative and distinct from cancer stem cells. These data support the concept that tumours contain discrete stem, proliferative and differentiation compartments similar to that present in normal crypts.
Dietary intake is an important modifiable risk factor for the metabolic syndrome, prediabetes, and overweight. Dried plums are nutrient‐dense and promote modest acute glycemic and insulinemic responses, which are considered favorable for these populations. Twenty‐one adults meeting the criteria for the metabolic syndrome, prediabetes, or clinical overweight consumed a whole food (dried plums;n=11) or refined (low‐fat muffins;n=10) snack, twice daily for eight weeks. Snacks provided 100 kcal/feeding and were similar in macronutrients but differed in fiber and other constituents. Intake was assessed via multiple 24‐hour food recalls obtained prior to and during the test food intervention. Dried plum consumers ingested greater (p<0.05) daily amounts of potassium, copper, and magnesium during the intervention period than pre‐intervention, whereas muffin eaters exhibited no significant differences in those nutrients but increased thiamin, riboflavin and iron intake. The muffin group consumed more energy during the intervention period than pre‐intervention (p<0.05, 95% CI∆ 61 to 762). Results suggest that proper snack selection is a viable avenue for improving dietary intake in the populations studied. Grant Funding Source: Supported by the California Dried Plum Board
The effects of a whole food (dried plums; DP) or refined (low‐fat muffins; LFM) snack on satiety and insulin responses following consumption were assessed before and after a snack intervention trial. Forty overweight men and women (age: 36.5 + 11.4, BMI: 32.8 + 7.1 kg/m2) were randomly assigned to consume isocaloric, macronutrient‐matched 100 kcal snacks twice per day of DP or LFM for 8‐weeks. At baseline and 8 weeks, fasted subjects consumed 238 kcal of their randomly assigned food, and blood samples were collected at baseline, 15, 30, 45, 60, 90, and 120 min following intake. Insulin was lower (p蠄0.05) and an earlier peak was observed in DP versus LFM at baseline and 8 weeks. Both groups exhibited lower plasma glucose during the acute response testing after 8 weeks, but glucose peaked earlier in DP than LFM. There were no significant differences in ghrelin concentration over time in either group. These results support the concept that consuming a whole food snack such as dried plums enhances insulin sensitivity as compared to an isocaloric refined snack food, as evidenced by lower insulin concentrations and an earlier peak in insulin and glucose in DP compared to LFM. Grant Funding Source: Supported by the California Dried Plum Board
Adipose tissue is a major energy reserve of the human body. It is also a source of the primary adpidocytokines leptin and adiponectin. The expression of adiponectin, specifically high‐molecular weight adiponectin (HMW‐A), and leptin have been demonstrated to decrease and increase, respectively, in relation to an increase in subcutaneous fat. Furthermore, HMW‐A and high sensitivity C‐reactive protein (hs‐CRP) have been demonstrated to have a reciprocal relationship. Effects of eight weeks of twice daily snacking (100 kcals each) of either a whole food (dried plums) or refined food (low‐fat muffins) on adipokines, body composition and hs‐CRP were assessed. HMW‐A decreased from baseline to eight weeks (p<.05) during the muffin intervention, demonstrating a non‐significant, two‐fold greater decrease than during the dried plum trial. No difference was seen in body weight, body composition, leptin or hs‐CRP. This suggests that the addition of energy through snacking to usual dietary intake, regardless of nutrient composition, may not be advantageous in promoting anthropometric or metabolic alterations in overweight individuals. Grant Funding Source: Supported by the California Dried Plum Board
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