ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells.

PURPOSE: ZD1839 is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that has shown clinical activity against EGFR-expressing tumors. Our aim was to explore the effects of ZD1839 in breast cancer cell lines expressing different levels of EGFR and the closely related HER2 receptor. EXPERIMENTAL DESIGN: We studied the growth-inhibitory effects of ZD1839 in a series of breast carcinoma cell lines. In HER2-overexpressing BT-474 breast cancer cells, we studied the effects of ZD1839 on cell growth and heterodimerization of receptors under basal and ligand-stimulated conditions. RESULTS: ZD1839 was an equally potent inhibitor of growth in breast cancer cells expressing high levels of EGFR and HER2. In BT-474 breast cancer cells, ZD1839 abolished EGF- and heregulin-induced activation of ErbB receptors and downstream signaling molecules. Because ZD1839 does not inhibit the HER2 tyrosine kinase in vitro, and because heregulin is a ligand that activates HER2 by binding to HER3 and HER4 but does not bind to the EGFR, our findings suggested that ZD1839 interfered with HER2 function in intact cells. Searching for mechanisms, we report that ZD1839 induces the formation of inactive unphosphorylated EGFR/HER2 and EGFR/HER3 heterodimers. Furthermore, ZD1839 completely abolishes basal and heregulin-induced formation of active phosphorylated HER2/HER3 heterodimers. CONCLUSIONS: ZD1839 inhibits the growth of HER2-overexpressing breast cancer cells, possibly by sequestration of HER2 and HER3 receptors in an inactive heterodimer configuration with the EGFR. Our findings suggest that there is a strong rationale to conduct clinical trials of ZD1839 in patients with HER2-overexpressing breast tumors.     

Prevention of central venous catheter-related bloodstream infections using non-technologic strategies.

OBJECTIVE: To evaluate the incidence of nosocomial bacteremias related to the use of non-impregnated central venous catheters (CVCs) when only non-technologic strategies were used to prevent them. DESIGN: This was a prospective study of infectious complications of CVCs placed in intensive care unit (ICU) patients from April 1997 to December 2001. SETTING: The medical-surgical ICU of a tertiary-care, university-affiliated hospital in Argentina. METHODS: We studied all patients admitted to the ICU using non-impregnated CVCs. Maximal sterile barrier precautions (ie, use of cap, mask, sterile gown, sterile gloves, and large sterile drape), strict handwashing, preparation of the patients' skin with antiseptic solutions, insertion and management of catheters by trained personnel, and continuing quality improvement programs aimed at appropriate insertion and maintenance of catheters were employed. RESULTS: During the study period, 2,525 patients were admitted to the ICU. Eight hundred sixty-eight patients had 1,037 CVCs inserted. The number of CVC-related bloodstream infections (BSIs), acquired in the ICU, was 2.7 per 1,000 CVC-days (13 nosocomial CVC-related BSIs during 4,770 days of CVC use). Microorganisms isolated included methicillin-susceptible Staphylococcus aureus (n = 6), methicillin-resistant S. aureus (n = 2), coagulase-negative methicillin-resistant Staphylococcus (n = 2), Escherichia coli (n = 1), Klebsiella pneumoniae (n = 1), and Enterobacter cloacae (n = 1). CONCLUSIONS: A low rate of catheter-related BSI was achieved without antimicrobial-impregnated catheters. The incidence of CVC-associated bacteremias corresponded to the 10th to 20th percentile range of the National Nosocomial Infections Surveillance System hospitals for the same type of ICU.     

Artificial intelligence for the early detection of colorectal cancer: A comprehensive review of its advantages and misconceptions

Colorectal cancer (CRC) was the second-ranked worldwide type of cancer during 2020 due to the crude mortality rate of 12.0 per 100000 inhabitants. It can be prevented if glandular tissue (adenomatous polyps) is detected early. Colonoscopy has been strongly recommended as a screening test for both early cancer and adenomatous polyps. However, it has some limitations that include the high polyp miss rate for smaller (< 10 mm) or flat polyps, which are easily missed during visual inspection. Due to the rapid advancement of technology, artificial intelligence (AI) has been a thriving area in different fields, including medicine. Particularly, in gastroenterology AI software has been included in computer-aided systems for diagnosis and to improve the assertiveness of automatic polyp detection and its classification as a preventive method for CRC. This article provides an overview of recent research focusing on AI tools and their applications in the early detection of CRC and adenomatous polyps, as well as an insightful analysis of the main advantages and misconceptions in the field.     

Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter,Randomized, Double-Blind,Placebo-Controlled Trial

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