CFTR potentiator VRT-532 increased ARSB expression and activity in cystic fibrosis cells to the level in the normal bronchial epithelial cells. Role in malignancy
ARSB has been studied in a variety of cancers. Cultured normal mammary epithelial and myoepithelial cells had significantly higher ARSB activity than cultured malignant mammary cells. Immunohistochemistry  in the colon showed decreased membrane ARSB staining in colon cancer compared to normal colon, as well as in higher grade malignancies. ARSB activity was lower in malignant than normal prostate tissue, and immunostaining of prostate tissue microarrays showed not only decreasing ARSB staining in prostate cancer tissue of a higher Gleason score, but also lower staining in patients with recurrent compared to non-recurrent cancer. ARSB staining was a greater predictor of recurrence than Prostate-specific antigen (PSA) test, indicating possible future role of ARSB as a prognostic biomarker of prostate cancer. Further evidence of ARSB as a tumor suppressor was determined by molecular studies in cell cultures where ARSB was silenced by siRNA. The studies showed that decrease of ARSB leads to increase in free galectin-3, which attaches more strongly to less sulfated chondroitin 4-sulfate. Galectin-3 then acts on transcription factors AP-1 to increase expression of chondroitin sulfate proteoglycan versican and SP-1 to increase expression of WNT9A. Another mechanism by which reduced ARSB is associated with carcinogenesis is through increased binding of SHP2 to more sulfated chondroitin 4-sulfate, which leads to increased phosphorylation of p38 and MITF with subsequently increased expression of GPNMB.
This is useful because chronic pneumonias tend to be either non-infectious, or mycobacterial, fungal, or mixed bacterial infections caused by airway obstruction. Acute pneumonias are further divided into the classic bacterial bronchopneumonias (such as Streptococcus pneumoniae), the atypical pneumonias (such as the interstitial pneumonitis of Mycoplasma pneumoniae or Chlamydia pneumoniae), and the aspiration pneumonia syndromes.Chronic pneumonias, on the other hand, mainly include those of Nocardia, Actinomyces and Blastomyces dermatitidis, as well as the granulomatous pneumonias (Mycobacterium tuberculosis and atypical mycobacteria, Histoplasma capsulatum and Coccidioides immitis).The combined clinical classification, now the most commonly used classification scheme, attempts to identify a persons risk factors when he or she first comes to medical attention. The advantage of this classification scheme over previous systems is that it can help guide the selection of appropriate initial treatments even before the microbiologic cause of the pneumonia is known. There are two broad categories of pneumonia in this scheme: community-acquired pneumonia and hospital-acquired pneumonia. A recently introduced type of healthcare-associated pneumonia (in patients living outside the hospital who have recently been in close contact with the health care system) lies between these two categories. References


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