Poly(ADP-ribose) polymerase activation is an immediate cellular response to metabolic-, chemical-, or ionizing radiation-induced DNA damage and represents a new target for cancer therapy. In this article, we disclose a novel series of substituted 4-benzyl-2 H-phthalazin-1-ones that possess high inhibitory enzyme and cellular potency for both PARP-1 and PARP-2. Optimized compounds from the series also demonstrate good pharmacokinetic profiles, oral bioavailability, and activity in vivo in an SW620 colorectal cancer xenograft model. 4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2 H-phthalazin-1-one (KU-0059436, AZD2281) 47 is a single digit nanomolar inhibitor of both PARP-1 and PARP-2 that shows standalone activity against BRCA1-deficient breast cancer cell lines. Compound 47 is currently undergoing clinical development for the treatment of BRCA1- and BRCA2-defective cancers.
A parotid gland abscess is uncommon and if not responding to conservative management, requires surgical intervention. However, surgery is invasive with the risk of complicating facial nerve damage and possible poor cosmetic outcome. We present a case of a parotid gland abscess in association with an underlying Warthin's tumour requiring percutaneous drainage, as patient co-morbidity precluded a safe surgical approach. Percutaneous drainage was aided by a contrast-enhanced ultrasound examination, which permitted delineation of the fluid aspects of the collection from the underlying tumour and allowed successful percutaneous ultrasound-guided aspiration without complication.
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