45 research outputs found

    Combined changes in Wnt signalling response and contact inhibition induce altered proliferation in radiation treated intestinal crypts

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    Curative intervention is possible if colorectal cancer is identified early, underscoring the need to detect the earliest stages of malignant transformation. A candidate biomarker is the expanded proliferative zone observed in crypts before adenoma formation, also found in irradiated crypts. However, the underlying driving mechanism for this is not known. Wnt signaling is a key regulator of proliferation, and elevated Wnt signaling is implicated in cancer. Nonetheless, how cells differentiate Wnt signals of varying strengths is not understood. We use computational modeling to compare alternative hypotheses about how Wnt signaling and contact inhibition affect proliferation. Direct comparison of simulations with published experimental data revealed that the model that best reproduces proliferation patterns in normal crypts stipulates that proliferative fate and cell cycle duration are set by the Wnt stimulus experienced at birth. The model also showed that the broadened proliferation zone induced by tumorigenic radiation can be attributed to cells responding to lower Wnt concentrations and dividing at smaller volumes. Application of the model to data from irradiated crypts after an extended recovery period permitted deductions about the extent of the initial insult. Application of computational modeling to experimental data revealed how mechanisms that control cell dynamics are altered at the earliest stages of carcinogenesis

    Improvement of endoscopic laser therapy in gastrointestinal ulcer bleeding by tissue infiltration basic experiments on the dog stomach<em> in vivo.</em>

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    The therapeutic effect of Nd-YAG laser coagulation in arterial ulcer bleeding seems to be improved by local epinephrine infiltration. The purpose of this animal study was to evaluate the safety of this new therapeutic modality. The effect of Nd-YAG laser on normal and on infiltrated gastric mucosa was compared in acute and chronic experiments on 14 beagle dogs. On exposed normal gastric wall, perforation time and power output were inversely correlated. The required energies are nearly constant at different power levels. After infiltration of sodium chloride as well as of epinephrine into the mucosa, however, perforation time increased four- to live-fold. Volumes of mucosa defects and of the coagulation zones were also lower after pretreatment by infiltration. The results encourage further clinical use of this new therapeutic approach
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