Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w

The Evidence for a Pentaquark Signal and Kinematic Reflections

Several recent experiments have reported evidence for a narrow baryon resonance with positive strangeness ($\Theta^+$) at a mass of 1.54 GeV/$c^2$. Baryons with $S=+1$ cannot be conventional $qqq$ states and the reports have thus generated much theoretical speculation about the nature of possible $S=+1$ baryons, including a 5-quark, or pentaquark, interpretation. We show that narrow enhancements in the $K^+n$ effective mass spectrum can be generated as kinematic reflections resulting from the decay of mesons, such as the $f_2(1275)$, the $a_2(1320)$ and the $\rho_3(1690)$.Comment: 4 pages, 4 figure

Інноваційна конкурентоспроможність в умовах глобалізації

BACKGROUND Associations between acute respiratory inflammatory responses, changes in bronchial hyperresponsiveness, serum pneumoprotein levels, and exposure to fire smoke were studied. METHODS The study comprised 51 firefighters. Blood samples were taken within 24 hr following exposure to fire smoke, and after a week and 3 months. Sputum was induced within 5 days post-exposure and subjects underwent spirometry and methacholine provocation one week post-exposure. Exposure was registered by a questionnaire. RESULTS No changes were observed following smoke exposure in bronchial hyperresponsiveness and serum pneumoprotein levels. Nevertheless, in a sizable proportion of the firefighters (44%) elevated sputum neutrophil levels (≥60%) were found. Serum IL-8 concentrations were higher 24 hr post-exposure compared to pre-exposure. Elevated neutrophil levels in sputum were associated with elevated serum IL-8 (β = 0.010, P = 0.004) and TNFα (β = 0.005, P = 0.034) levels within 24 hr post-exposure and IL-8 elevation lasted up to 3 months. CONCLUSIONS Acute exposure to fire smoke induces acute neutrophilic airway and long-lasting systemic inflammation in healthy firefighters in the absence of bronchial hyperresponsiveness. Am. J. Ind. Med. 55:54-62, 2012. © 2011 Wiley Periodicals, Inc

Oral Lubrication Matters: Effects on Satiety

As overeating, overweight and obesity remain public health concerns, it is crucial to design satiety-enhancing foods that suppress appetite and lower snack intake. Existing research identifies oro-sensory targets to promote satiation and satiety within the “satiety cascade” yet it remains unclear as to whether it is ‘chewing’ or ‘oral lubrication’ that might amplify satiation signals.Here we have combined techniques from experimental psychology, food material science and mechanical engineering to measure the role of chewing and lubrication using novel, model foods as preloads on subjective appetite and intake of a salty snack. Three mint flavoured hydrogels were engineered to vary in their texture (fracture stress) and lubrication (inverse of friction coefficient) properties, and a control group received a mint tea. Results showed that snack intake was suppressed by 32% after eating the low chewing/high lubricating preload as compared to the high chewing/low lubricating preload (p<0.05). No other significant effects were found for snack intake. Hunger ratings decreased from t1 to t3 (p<0.05), however differences between conditions were subtle and not significant. Thus, this proof-of-concept study demonstrates that manipulating oral lubrication is a promising new construct to reduce snack intake that merits future research in the oro-sensory satiety domain

Development of a Sandwich ELISA to Measure Exposure to Occupational Cow Hair Allergens

Background: Cow hair and dander are important inducers of occupational allergies in cattle-exposed farmers. To estimate allergen exposure in farming environments, a sensitive enzyme immunoassay was developed to measure cow hair allergens. Methods: A sandwich ELISA was developed using polyclonal rabbit antibodies against a mixture of hair extracts from different cattle breeds. To assess the specificity of the assay, extracts from other mammalian epithelia, mites, molds and grains were tested. To validate the new assay, cow hair allergens were measured in passive airborne dust samples from the stables and homes of farmers. Dust was collected with electrostatic dust fall collectors (EDCs). Results: The sandwich ELISA was found to be very sensitive (detection limit: 0.1 ng/ml) and highly reproducible, demonstrating intra-and interassay coefficients of variation of 4 and 10%, respectively. The assay showed no reactivity with mites, molds and grains, but some cross-reactivity with other mammalian epithelia, with the strongest reaction with goat. Using EDCs for dust sampling, high concentrations of bovine allergens were measured in cow stables (4,760-559,400 mu g/m(2)). In addition, bovine allergens were detected in all areas of cattle farmer dwellings. A large variation was found between individual samples (0.3-900 mu g/m(2)) and significantly higher values were discovered in changing rooms. Conclusion: The ELISA developed for the detection of cow hair proteins is a useful tool for allergen quantification in occupational and home environments. Based on its low detection limit, this test is sensitive enough to detect allergens in passive airborne dust. Copyright (C) 2011 S. Karger AG, Base

On relating rheology and oral tribology to sensory properties in hydrogels

The aim of this study was to understand the relationship between rheological, tribological and sensory properties (n = 11 panellists) of hydrogels differing in hydrocolloid type, concentration and degree of inhomogeneity. Fracture properties of hydrogels containing different ratios of κ-carrageenan (κC) and/or locust bean gum (LBG), sodium alginate (NaA), 300/1000 μm calcium alginate beads (CaA) at 1–4 wt% concentration were determined. Viscosity and friction coefficients (μ) of the hydrogel-boli after simulated oral processing were characterized. Tribology measurements were conducted in a polydimethylsiloxane ball/disc set-up with pre-adsorbed artificial salivary film at 37 °C. ’Scaling’ with boli viscosity showed good agreement of observed data with the Stribeck master curve, however only in the mixed regime i.e. at intermediate values of the product of velocity and lubricant viscosity (Uη). Low μ values of gel boli in the boundary regime were largely driven by the formation of a viscous layer of bolus fragments between opposing surfaces. Fracture properties of hydrogels and boli viscosity were correlated with all chewing-related texture attributes i.e. ‘firm’, ‘elastic’, ‘chewy’ and ‘cohesive’ and inversely correlated with lubrication-related attributes ‘melting’ and ‘pasty’ (p<0.05). On the other hand, μ of the bolus filtrate at orally relevant speeds (50 mm/s) was inversely correlated with lubrication-related attributes ‘pasty’ and positively with ‘slippery’ (p<0.05). The lack of correlations with ‘smooth’ could be explained due to sample inhomogeneity and the absence of ‘ball-bearing’-ability of the gel beads. A combination of initial fracture properties, boli viscosity and tribology of bolus filtrates (mixed regime) impacted the lubrication-related attribute ‘salivating’ (p<0.05)