Metastases's spreading is the main cause of mortality for advanced stage cancer patients, including melanoma. The formation of metastases is favored by enhanced migratory and invasive capacities of tumor cells. Tumor suppressor gene
NF1
is a negative regulator of RAS and its deregulation plays an important role in several aspects of melanoma transformation and progression. However, very little is described about the role of NF1 in cellular migration and invasion. In this study, our results show on the one hand, that the loss of NF1 expression delays migration of human melanoblasts
via
a RAC1-dependent mechanism. On the other hand, our data indicate that NF1 loss in melanoma cells is enhancing migration, intravasation and metastases formation
in vivo
. Moreover, not only this phenotype is associated with an upregulation of PREX1 but also patient-derived melanoma samples with low NF1 expression present increased levels of PREX1. In sum, our study brings new elements on the mechanism controlling cellular migration in the context of
NF1
loss. These data are of prime interest to improve treatment strategies against all
NF1
-mutated tumors, including this subtype of melanoma.
Objectives. Type 2 diabetes mellitus (T2DM) is a major global public health issue. Diet and physical exercise are modifiable factors that influence the glycaemic status of patients with T2DM. We aimed to investigate the acute effects of breakfast fruits meal sequence and postprandial exercise on the blood glucose level and dipeptidyl peptidase 4 (DPP4) activity among type 2 diabetes mellitus patients. Methods. A randomized pilot study recruited patients with T2DM who attended two primary health care centres in Tasikmadu District, Karanganyar Regency, and Kartasura District, Sukoharjo Regency, Central Java, Indonesia, from July to October 2016. Eligible patients (4 men and 32 women) were randomly divided into four treatment groups. Venous blood samples were analyzed for fasting and one-hour postprandial blood glucose (FBG and 1 h PPG) levels and DPP4 activity. Blood glucose levels were measured using a routine hexokinase method, and serum DPP4 activity was determined spectrophotometrically after incubation with the Gly-Pro-p-nitroanilide substrate. Results. Fruits last meal decreased FBG level whilst fruits first meal did not significantly decrease 1 h PPG level. Both treatments had no acute effects on DPP4 activity but the addition of postprandial exercise helped lower DPP4 activity. Fruit last and first meals showed significant opposite effects on mean changes of FBG level (
p
<
0.05
). Conclusions. This preliminary report of fruits meal sequence is potentially involved in acute regulation of blood glucose levels and that it might be independent of DPP4 activity in Indonesian patients with T2DM. Moreover, postprandial exercise may be an important intervention for T2DM through the mediation of DPP4 but has no acute effects on the regulation of blood glucose levels. Further studies are required to investigate whether or not different types of fruits and longer treatment intervals can affect blood glucose levels and DPP4 activity differently. This study also gives an insight into the feasibility of conducting food order modification with or without the combination of postprandial exercise in a primary health setting for our next studies.
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