Page 172 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

projections of dendritic cells in immunity). Upon activation of the Src-Rho-Rac cascade by Hedgehog, actin cytoskeleton reorganization takes place independent of the activity of any transcription factor and necessary for the functionality of Sonic Hedgehog in physiology. This provoking idea suggests that Hedgehog signaling might regulate a cohort of physiological processes involving fluctuations of Ca2+, acutely affecting membrane potential and Ca2+-dependent signaling pathways, as my promotor showed during his PhD research on the link between actin reorganization and calcium fluxes. But obviously further research is necessary to substantiate this notion. My findings on the new role of Hedgehog in actin cytoskeleton reorganization has thus prompted me to suggest further studies on the interactive parts of Sonic Hedgehog with other morphogenetic cascades during development and formation of dendritic projections.
In chapter 5 gastric atrophy has been described as a precancerous condition and can be evaluated through routine endoscopy. Several studies assessed the agreement level in a variety of methods between endoscopy and histologic atrophy but differ in sensitivity, specificity, precision, and accuracy due to the lack of a gold standard to compare if the grouping is suitable or not. Information from our study on endoscopic grading evaluation has shown a reproducible kappa value, and such grading can be used to predict the precancerous condition of histologic atrophy during routine H. pylori screening practice in Africa and Middle-east.
In chapter 6 we looked at the diversity of Helicobacter pylori genotypes and development of gastric cancer. Our results showed the relationship of babA2, babB negative and iceA1 positive genotype and the development of cases of gastric cancer was statistically significant. Further studies are required to determine the functions of babA2 and babB and their relationship with disease outcome, and whether the presence of these alleles indicates the presence of bacteria unlikely to confer progression towards gastric carcinoma.
As evident from the above, it may prove necessary to stimulate immunity during full-blown gastric cancer. Immunocheckpoint-directed therapy may prove a way forward here, but may not be sufficient to reach the desired level of anticancer immunity. Knowledge of pathways that constrain immunity might help in this respect as the inhibition of those pathways may further stimulate anti-cancer immunity. In chapter 7 I explore this aspect by evaluating the effect of microgravity as an approach. Space travel is associated with diminished immunity
Chapter 8
Chapter 8
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