Non‐clinical safety evaluation of single and repeated intramuscular administrations of MAGE‐A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys

The MAGE‐A3 recombinant protein combined with AS15 immunostimulant (MAGE‐A3 Cancer Immunotherapeutic) is under development by GlaxoSmithKline for the treatment of lung cancer and melanoma. We performed non‐clinical safety studies evaluating potential local and systemic toxic effects induced by MAGE‐A3 Cancer Immunotherapeutic in rabbits (study 1) and cynomolgus monkeys (study 2). Animals were allocated to two groups to receive a single (rabbits) or 25 repeated (every 2 weeks) injections (monkeys) of MAGE‐A3 Cancer Immunotherapeutic (treatment groups) or saline (control groups). All rabbits were sacrificed 3 days post‐injection and monkeys 3 days following last injection (3/5 per gender per group) or after a 3‐month treatment‐free period (2/5 per gender per group). Local and systemic reactions and MAGE‐A3‐specific immune responses (monkeys) were assessed. Macroscopic and microscopic (for rabbits, injection site only) post‐mortem examinations were performed on all animals. No systemic toxicity or unscheduled mortalities were recorded. Single (rabbits) and repeated (monkeys; up to four times at the same site) injections were well tolerated. Following five to seven repeated injections, limb circumferences increased up to 26% (5 h post‐injection), but returned to normal after 1–8 days. Three days after the last injection, enlargements of iliac, popliteal, axillary and inguinal lymph nodes, and increased incidence or severity of mononuclear inflammatory cell infiltrates was observed in injected muscles of treated monkeys. No treatment‐related macroscopic findings were recorded after the treatment‐free period. MAGE‐A3‐specific antibody and T‐cell responses were raised in all treated monkeys, confirming test item exposure. Single or repeated intramuscular injections of MAGE‐A3 Cancer Immunotherapeutic were well tolerated in rabbits and monkeys. Copyright © 2014 GlaxoSmithKline Vaccines. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.     

Ventilation/perfusion (V/Q) scanning in contemporary patients with pulmonary embolism: utilization rates and predictors of use in a multinational study

Journal of Thrombosis and Thrombolysis - Ventilation/perfusion (V/Q) imaging and computed tomography pulmonary angiography (CTPA) are common tools for acute pulmonary embolism (PE) diagnosis....     

Lymphocytic hypophysitis with lachrymal, salivary and thyroid gland involvement

We report on hypophysitis associated with a prominent lymphoid infiltration of salivary and lachrymal glands in a 35-year-old woman with a dramatic response to steroids. Four years later, overt Graves' disease developed. To our knowledge, pseudotumoral lymphocytic infiltration of both lachrymal and salivary glands has never been described in association with hypophysitis. Benign lymphocytic hypophysitis may belong to a spectrum that extends from low-grade lymphoid proliferation to autoimmune disease. Such a process may follow a regional tissue distribution including pituitary, thyroid, lachrymal and salivary glands.     

Evaluation of Epstein-Barr Virus,Human Herpesvirus 6 (HHV-6), and HHV-8 Antiviral Drug Susceptibilities by Use of Real-Time-PCR-Based Assays

Evaluation of candidate antiviral drugs against Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and HHV-8 is hampered by the lack of convenient laboratory assays. We developed real-time quantitative PCR assays performed on supernatants of lymphoma cell lines and determined the 50% inhibitory concentrations (IC₅₀s) of nucleoside, nucleotide, and pyrophosphate analogues against these herpesviruses.     

Candida guilliermondii: biotechnological applications, perspectives for biological control, emerging clinical importance and recent advances in genetics

Candida guilliermondii (teleomorph Meyerozyma guilliermondii) is an ascomycetous species belonging to the Saccharomycotina CTG clade which has been studied over the last 40 years due to its biotechnological interest, biological control potential and clinical importance. Such a wide range of applications in various areas of fundamental and applied scientific research has progressively made C. guilliermondii an attractive model for exploring the potential of yeast metabolic engineering as well as for elucidating new molecular events supporting pathogenicity and antifungal resistance. All these research fields now take advantage of the establishment of a useful molecular toolbox specifically dedicated to C. guilliermondii genetics including the construction of recipient strains, the development of selectable markers and reporter genes and optimization of transformation protocols. This area of study is further supported by the availability of the complete genome sequence of the reference strain ATCC 6260 and the creation of numerous databases dedicated to gene ontology annotation (metabolic pathways, virulence, and morphogenesis). These genetic tools and genomic resources represent essential prerequisites for further successful development of C. guilliermondii research in medical mycology and in biological control by facilitating the identification of the multiple factors that contribute to its pathogenic potential. These genetic and genomic advances should also expedite future practical uses of C. guilliermondii strains of biotechnological interest by opening a window into a better understanding of the biosynthetic pathways of valuable metabolites.