Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.

No abstract

No abstract

Hepatocellular carcinoma (HCC) arises in the context of cirrhosis and chronic hepatitis B virus (HBV) infections, and the diagnosis is often made at advanced stages. Because early-stage diagnosis improves survival, guidelines recommend screening patients at risk for HCC, such as patients with cirrhosis. However, adherence to screening programs is suboptimal. In this review, we discuss the value of HCC screening and provide practical guidance on patient selection and screening methods. International guidelines concordantly recommend HCC screening in patients with cirrhosis, including patients with HBV infections, hepatitis C virus infections with or without sustained virologic response, and nonalcoholic fatty liver disease. There is no consensus on screening patients without cirrhosis, although patients with advanced fibrosis, HBV infections, or nonalcoholic fatty liver disease without cirrhosis have an increased risk for development of HCC. Screening for HCC improves early tumor detection, receipt of curative treatment, and overall survival in at-risk patients. However, potential harms of HCC screening have not been well quantified. Semiannual abdominal ultrasonography is the screening modality of choice. Using ultrasonography in combination with biomarkers, such as a-fetoprotein, may increase accuracy for early HCC detection. The use of magnetic resonance imaging and computed tomography is limited by costeffectiveness and practical considerations. Increased awareness of HCC screening will allow for earlier diagnosis and potentially curative treatment. We propose a comprehensive screening algorithm for patients at risk for development of HCC, recommending lifelong, semiannual ultrasonography combined with a-fetoprotein testing in patients with cirrhosis and selected patients without cirrhosis.

BPH ¼ benign prostatic hyperplasia, IIEF ¼ International Index of Erectile Function, IPSS ¼ International Prostate Symptom Score, LUTS ¼ lower urinary tract symptoms, MIST ¼ minimally invasive surgical therapies, OP ¼ open prostatectomy, PAE ¼ prostatic artery embolization, PVR ¼ postvoid residual, QOL ¼ quality of life, RCT ¼ randomized controlled trial, TURP ¼ transurethral resection of the prostate, UK-ROPE ¼ United Kingdom Register of Prostate Embolization BACKGROUND Benign prostatic hyperplasia (BPH) describes the proliferation of the glandular and stromal tissue in the transition zone of the prostate, which may result in bladder outlet obstruction and consequent lower urinary tract symptoms (LUTS). The prevalence of BPH increases with age, affecting more than 70% of men older than 70 years (1), and one fourth of men older than 70 years have moderate to severe LUTS that impair their quality of life (QOL) (2,3). Thus, BPH and ensuing LUTS represent a significant health issue affecting millions of men. The International Prostate Symptom Score (IPSS; also known as the American Urologic Association Symptom Index) is a validated instrument that quantifies a patient's subjective urinary symptoms on a 35-point scale (4). The IPSS also incorporates a urinary QOL score, which assesses how the patient feels overall about his urinary symptoms. Nearly all studies assessing BPH treatments for LUTS use the IPSS and QOL scores to assess patients before and after treatment. A 3-point change in IPSS is noticeable by a man with LUTS (5), and a 30% reduction in IPSS is considered clinically acceptable for a treatment to be considered effective (6,7). Medical therapies, including a-1 blockers and 5-a reductase inhibitors, are the mainstay of treatment for mild to moderate LUTS. The symptomatic relief is relatively modest, with IPSS improvement in the range of 3-7 points (8). Although generally considered safe, medical