In summary, our studies, for the first time, demonstrate transcriptional regulation of DRA expression by CDX2, implying that reduced expression of DRA in inflammatory bowel disease-associated diarrhea may, in part, be due to downregulation of CDX2 in the inflamed mucosa.<b>NEW & NOTEWORTHY</b> SLC26A3 [downregulated in adenoma (DRA)] mediates intestinal luminal NaCl absorption and is downregulated in inflammatory bowel disease-associated diarrhea.
Although EGFR TKIs are commonly associated with skin-related (rash, xerosis and paronychia) and gastrointestinal-related (diarrhea and stomatitis) adverse events (AEs), these effects are usually mild.
The metabolic alkalosis of congenital chloride-losing diarrhea is caused by mutations in the DRA Cl(-)/HCO3(-) exchanger of the ileocolonic apical membrane.
Congenital chloride diarrhea (CLD) is a rare, autosomal recessive disorder of intestinal Cl/HCO3 exchange caused by mutations in the SLC26A3 gene and characterized by persistent Cl rich diarrhea from birth.
A plethora of human diseases are associated with mutations in the genes encoding human SLC26 transporters, including chondrodysplasias with varying severity in SLC26A2 (~50 mutations, 27 point mutations), congenital chloride-losing diarrhea in SLC26A3 (~70 mutations, 31 point mutations) and Pendred Syndrome or deafness autosomal recessive type 4 in SLC26A4 (~500 mutations, 203 point mutations).
A consensus meeting of a UK-based multidisciplinary panel composed of medical and clinical oncologists with a special interest in lung cancer, dermatologists, gastroenterologists, lung cancer nurse specialists and oncology pharmacists was held to develop guidelines on prevention and management of cutaneous (rash, dry skin and paronychia) and GI (diarrhoea, stomatitis and mucositis) AEs associated with the administration of EGFR-TKIs.
After adjusting for performance status, previous platinum-containing chemotherapy and occurrence of skin rash or diarrhea during the first treatment cycle in patients with performance status 0 or 1 (N=139), the absence of EGFR*1 was associated with significantly better survival (hazard ratio: 0.54; 95% confidence interval: 0.32-0.91; P=0.015).
Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients.
Congenital chloride losing diarrhea (CCLD) is a rare type of chronic watery diarrhea due to mutations in SLC26A3 gene leading to defective chloride-bicarbonate exchanges with the resultant loss of chloride and retention of bicarbonate.We aim to define pediatric Saudi CCLD patients' characteristics to achieve prompt diagnosis, management, follow up with good quality of life, and prevention of complications in these patients.We carried retrospective data review of demographic, clinical, laboratory, radiographic, and outcome of all pediatric patients fulfilling the criteria of CCLD over 10 years from 2004 to 2014 from a single center in Taif region, Saudi Arabia.Forty-nine patients fulfilled the criteria of CCLD from 21 families with more than one affected patient in the same family in 90% of them and positive consanguinity in 91% of the cohort.
These findings indicate that EGFR -216G>T genotype is a predictive marker for the development of skin rash and diarrhoea in paediatric patients treated with gefitinib.
Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea.
Intestinal epithelial apical membrane Cl-/HCO3- exchanger DRA (downregulated in adenoma, SLC26A3) has emerged as an important therapeutic target for diarrhea, emphasizing the potential therapeutic role of agents that upregulate DRA.
Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma).
In evaluable HER2<sup>+</sup> MBC (<i>n</i> = 22) treated at doses ≥ MTD, the response rate was 14% [all partial response (PR)] and the clinical benefit rate (PR + stable disease ≥ 24 weeks) was 27%.<b>Conclusions:</b> ONT-380 had a lower incidence and severity of diarrhea and rash than that typically associated with current dual HER2/EGFR inhibitors and showed notable antitumor activity in heavily pretreated HER2<sup>+</sup> MBC patients, supporting its continued development.<i></i>.