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Biology subjects

Boros, M.

Publications and source records attributed to Boros, M..

2 recordsLinked to original sources

Predicting the evolution of lung squamous cell carcinoma in situ using deep learning

Lung squamous cell carcinoma in situ (SCIS) is the pre-invasive precursor lesion of lung squamous cell carcinoma (SCC). Only half of these lesions progress to invasive cancer, while a third undergo spontaneous regression. The ability to predict the evolution of SCIS lesions can significantly impact the management of lung cancer patients. Here, we present the use of the deep learning (DL) approach in order to predict the progression of SCIS. The dataset consisted of 112 H&E stained whole slide images (WSI) that were obtained from the Image Data Resource public repository. The data set corresponded to tumors of patients who underwent biopsies of SCIS lesions and were subsequently followed up by bronchoscopy and CT to monitor for progression to SCC. We show that a deep convolutional neural network (DCNN) can predict if a SCIS lesion will progress to SCC. The model achieved a per-tile AUC of 0.78 (SD = 0.01) on the test set, an F1 score of 0.84 (SD = 0.05), and a sensitivity of 0.94 (SD = 0.01). Class activation maps were created in order to explore how the DCNN made decisions. To our knowledge, this study is the first to demonstrate that DL has the ability to predict the evolution of SCIS from H&E WSI. DL has the potential to be used as a low-cost method that could provide prognostic information for patients with preinvasive lesions.

pathology↗

Hydrogen Peroxide Production by Epidermal Dual Oxidase 1 Regulates Nociceptive Sensory Signals

Keratinocytes of the mammalian skin provide not only mechanical protection for the tissues, but also transmit mechanical, chemical, and thermal stimuli from the external environment to the sensory nerve terminals. Sensory nerve fibers penetrate the epidermal basement membrane and function in the tight intercellular space among keratinocytes. Here we show that epidermal keratinocytes produce hydrogen peroxide upon the activation of the NADPH oxidase dual oxidase 1 (DUOX1). This enzyme can be activated by increasing cytosolic calcium levels. Using DUOX1 knockout animals as a model system we found an increased sensitivity towards certain noxious stimuli in DUOX1-deficient animals, which is not due to structural changes in the skin as evidenced by detailed immunohistochemical and electron-microscopic analysis of epidermal tissue. We show that DUOX1 is expressed in keratinocytes but not in the neural sensory pathway. The release of hydrogen peroxide by activated DUOX1 alters both the activity of neuronal TRPA1 and redox-sensitive potassium channels expressed in dorsal root ganglia primary sensory neurons. We describe hydrogen peroxide, produced by DUOX1 as a paracrine mediator of nociceptive signal transmission. Our results indicate that a novel, hitherto unknown redox mechanism modulates noxious sensory signals.

physiology↗