ABSTRACT
Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2 foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2 cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.
ABSTRACT
The purpose of this study was to elucidate the circumstances of patients with amyotrophic lateral sclerosis who were emergently admitted to hospital and to examine problems associated with discharge and transfer. We reviewed medical records for 3 years and identified 4 home discharged patients and 8 hospital transfer patients who had been urgently admitted to the neurology ward of Hospital A. Mean hospital stay was 77 days. All patients received 24-h noninvasive positive pressure ventilation immediately after hospitalization. After a mean 31 days of hospitalization, patients chose medical treatments and/or treatment facilities. Three patients changed to tracheostomy positive pressure ventilation and 2 patients opted for tracheostomy. Four patients had disagreements with their families and needed time to resolve their differences. Between 1 to 6 hospitals were asked to accept each patient for transfer. Decisionmaking about initiation of medical treatment for respiratory failure needs to done in the early stages of illness. Healthcare providers need cooperation between in-hospital and community services and must demonstrate excellent assessment skills to recognize the progression of illness and the patient’s acceptance of illness. In addition, it is essential that healthcare providers possess special support skills when patients are transferred from intermediate institutions to home care.
ABSTRACT
The following four possible pathways for itching sensation have been suggested by recent reports. 1) Histaminergic TRPV1-positive pathway: Although histamine-positive nerve fibers cannot strictly be classified as “itch specific” due to their excitation also by pure algogens (making them itch-selective), the existence of a subpopulation of nociceptors responsible for itching is strongly suggested. Moreover, the TRPV1-expressing neurons have been suggested to be the main sensors and mediators of itching. 2) Histaminergic TRPV1-negative pathway: The scratching behavior caused by itching was not different between capsaicin-pre-treated and vehicle-treated (control) mast cell-rich NC mice. This result suggests the existence of a capsaicin-insensitive (TRPV1-negative) histaminergic pathway. 3) Non-histaminergic PAR-2 pathway: Protease-activated receptor 2 (PAR-2) has been shown to play a role in the itching of atopic dermatitis (AD). The itch evoked by cowhage (a non-histaminergic pruritogen that activates PAR-2) is very similar in characteristics to the itch evoked by conditions such as AD. 4) Non-histaminergic serotonin (5-HT) pathway: 5-HT alone applied to the human skin evokes an itching sensation and has been suggested to be involved in the itching associated with pruritic diseases, such as polycythemia vera and cholestasis.