Single-Arm Study of Etanercept in Adult Patients with Moderate to Severe Rheumatoid Arthritis Who Failed Adalimumab Treatment.

Introduction: To evaluate the efficacy and safety of etanercept treatment in adult patients with moderate to severe rheumatoid arthritis (RA) who failed to respond (primary failure) or lost a satisfactory response (secondary failure) to adalimumab.

Methods: All patients discontinued prior adalimumab treatment and continued methotrexate with etanercept 50 mg once weekly for 24 weeks. The primary study endpoint was American College of Rheumatology 20% improvement criteria (ACR20) at week 12.

Penetration of anticancer drugs through tumour tissue as a function of cellular packing density and interstitial fluid pressure and its modification by bortezomib.

Background: Limited penetration of anticancer drugs in solid tumours is a probable cause of drug resistance. Our previous results indicate that drug penetration depends on cellular packing density and adhesion between cancer cells.

Methods: We used epithelioid and round cell variants of the HCT-8 human colon carcinoma cell lines to generate tightly and loosely packed xenografts in nude mice.

[Can tumor hypoxia be turned into a chemotherapeutic advantage?].

The heterogeneous vascular distribution and blood flow in solid tumors create areas of low oxygen partial pressure or hypoxic areas. Hypoxia acts as a stressor that perpetuates the malignant phenotype by increasing genomic instability, altering gene expression, and the tumor's metabolic microenvironment. The heterodimeric transcription factor, hypoxia inducible factor, HIF-1 (Hypoxia-Inducible Factor-1), allows tumor cells to adapt to their microenvironment by stimulating the expression of a large number of hypoxia-related genes.

The penetration of anticancer drugs through tumor tissue as a function of cellular adhesion and packing density of tumor cells.

To reach cancer cells in optimal quantities, therapeutic agents must be delivered to tumors through their imperfect blood vascular system, cross vessel walls into the interstitium, and penetrate multiple layers of tissue. Strategies to enhance drug penetration have potential to improve therapeutic outcome. The development of multicellular layers (MCLs), in which tumor cells are grown on a semipermeable Teflon support membrane, has facilitated quantification of drug penetration through solid tissue.