Photodynamic diagnostics of early gastric cancer:Complexity measures of gastric microcirculation and new model of metastatic adenocarcinoma of rat stomach

The detection of early gastric cancer that often develops asymptomatically is crucial for improving patient survival.The photodynamic diagnosis(PDD)of gastric cancer using 5-aminolevulinic acid/protoporphyrin IX(5-ALA/PpIX)has been reported in several studies.However,the selectivity of PDD of gastric tumor is poor with often false-positive results that require the development of new methods to improve PDD for early gastric cancer.Therefore,a measure of the complexity of gastric microcirculation(multi-scale entropy,MSE)and the detrendedfluctuation analysis(DFA)were applied as additional tools to detect early gastric cancer in rats.In this experimental study,we used our original model of metastatic adenocarcinoma in the stomach of a rat.To induce a gastric tumor,we used a long-term combination(for 9 months,which is 1/2 of the life of rats)of two natural factors,such as chronic stress(overpopulation being typical for modern cities)and the daily presence of nitrites in food and drinks,which are common ingredients added to processed meat andfish to help preserve food.Our results clearly show that both methods,namely,PDD using 5-ALA/PpIX and complexity/correlation analysis,can detect early gastric cancer,which was confirmed by histological analysis.Pre-cancerous areas in the stomach were detected as an intermediatefluorescent signal or MSE level between normal and malignant lesions of the stomach.However,in some cases,PDD with 5-ALA/PpIX produced a false-positivefluorescence of exogenousfluorophores due to its accumulation in benign and inflammatory areas of the mucosa.This fact indicates that the PDD itself is not sufficient for the correct diagnosis of gastric cancer,and the use of additional characteristics,e.g.,complexity measures or scaling exponents,can significantly improve the diagnostic accuracy of PDD of gastric cancer that should be confirmed in further clinical studies and applications.

Optical in vivo and ex vivo imaging of glioma cells migration via the cerebral vessels:Prospective clinical application of the beta2-adrenoreceptors blockade for glioma treatment

Malignant gliomas are highly invasive tumors that 1use the cerebral vessels for invasion due to high vascular fragility of the blood--brain barrier(BBB).On one hand,glioma is characterized by the BBB disruption,on the other hand,drug brain delivery via the BBB is a big challenge in glioma therapy.The limited information about vascular changes associated with glioma growth is a reason of slow progress in prevention of glioma development.Here,we present in vrivo and er vrivo study of the BBB disruption and glioma cells(GCs)migration in rats using fuorescence and confocal microscopy.We uncovered a local breach in the BBB in the main tumor mass but not within the border of normal and malignant cells,where the BBB was impermeable for high weight molecules.The migr ation of GCs were observed via the cerebral vessels with the intact BBB that was associated with macrophages infiltration.The mechanisms underlying glioma progression remain umknown but there is an evidence that the sympathetic nervous system(SNS)via activation of vascular beta2-adrenoreceptors(B2-ADRs)can play an important role in tumor metastasis.Our results clearly show an increase in the expression of vascular B2-ADRs and production of the beta arrestin-1-co-factor of B2-ADRs signaling pathway in rats with glioma.Pharmacological blockade of B2-ADRs reduces the BBB disruption,macrophages infiltration,GCs migration and increases survival rate.These data suggest that the blockade of B2-ADRs may be a novel adjuvant therapeutic strategy to reduce glioma progression and prevent metastasis。

Sex differences in cardiovascular control by nitric oxide in normotensive and hypertensive rats

R Nitric oxide probably plays an important role in mechanisms determining sexual dimorphism in the development of cardiovascular diseases, including hypertension. Because stress together with gender are significant cardiovascular risk factors, we studied the role nitric oxide in car-diovascular regulation in male and female nor-motensive and hypertensive rats under normal and stress conditions. Experiments were per-formed in mongrel normotensive and hyperten-sive (two kidney, one clip) rats of both sexes, weighing 200-250g. The study of mean arterial pressure and heart rate was carried out: 1) under control condition;2) during nitric oxide blo- ckade by NG-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, iv) 3) during 60 min immobilization stress and recovery;4) during 60 min immobi-lization stress + L-NAME and recovery. We found that the severity of hypertension in fe-males was lower than in males. We also ob-served that both normotensive and hyperten-sive females demonstrated more favorable pat-tern of cardiovascular responses to stress. At rest, nitric oxide blockade increased the mean arterial pressure and decreased the heart rate more effectively in female normotensive and hypertensive rats than in male groups. During stress, nitric oxide blockade modified the stress- induced cardiovascular responses more sig-nificantly in female normotensive and hyper-tensive rats compared with male groups. Our data show that both normotensive and hyper-tensive females demonstrated the more effec-tive nitric oxide control of cardiovascular activ-ity under normal and especially stress condi-tions than male groups. This male-female dif-ference may be important mechanism respon-sible for greater in females vs. males of cardio-vascular resistance to stress and development of hypertension.