Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial.

BACKGROUND: Progression-free survival was significantly longer in patients who received avelumab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma (aRCC) in a randomized phase III trial. We report long-term safety and efficacy of avelumab plus axitinib as first-line treatment for patients with aRCC from the JAVELIN Renal 100 phase Ib trial (NCT02493751). MATERIALS AND METHODS: In this open-label, multicenter, phase Ib study, patients with untreated aRCC received avelumab 10 mg/kg every 2 weeks plus axitinib 5 mg twice daily or with axitinib for 7 days followed by avelumab plus axitinib. Safety and efficacy were assessed in all patients receiving at least one dose of avelumab or axitinib. RESULTS: Overall, 55 patients were enrolled and treated. Median follow-up was 55.7 months (95% CI, 54.5-58.7). Treatment-related adverse events of any grade or grade ≥3 occurred in 54 (98.2%) and 34 (61.8%) patients, respectively. The confirmed objective response rate was 60.0% (95% CI, 45.9-73.0), including complete response in 10.9% of patients. Median duration of response was 35.9 months (95% CI, 12.7-52.9); the probability of response was 65.8% (95% CI, 46.7-79.4) at 2 years. Median progression-free survival was 8.3 months (95% CI, 5.3-32.0). Median overall survival was not reached (95% CI, 40.8-not estimable); the 5-year overall survival rate was 57.3% (95% CI, 41.2-70.5). CONCLUSION: Five-year follow-up for combination treatment with avelumab plus axitinib in previously untreated patients with aRCC showed long-term clinical activity with no new safety signals, supporting use of this regimen within its approved indication in clinical practice (Clinicaltrials.gov NCT02493751)

Correlation of the ratio of metastatic to non-metastatic cancer cases with the degree of socioeconomic deprivation among Texas counties

<p>Abstract</p> <p>Background</p> <p>Previous studies have demonstrated that cancer registrations and hospital discharge rate are closely correlated with census data-based socioeconomic deprivation indices. We hypothesized that communities with higher degrees of socioeconomic deprivation tend to have a higher ratio of metastatic to non-metastatic cancer cases (lung, breast, prostate, female genital system, colorectal cancers or all types of cancers combined). In this study, we investigate the potential link between this ratio and the Wellbeing Index (WI) among Texas counties.</p> <p>Results</p> <p>Cancer data in 2000 were provided by the Texas Cancer Registry, while data on the ten socioeconomic variables among the 254 Texas counties in 2000 for building the WI were obtained from U.S. Census Bureau. The ten socioeconomic status variables were subjected to the principal component analysis, and the first principal component scores were grouped into deciles for the WI (1 to 10) and the 254 Texas counties were classified into 10 corresponding groups. Weighted linear regression analyses and a Cochran-Armitage trend test were performed to determine the relationship between the ratio of age-adjusted metastatic to non-metastatic cancer incidence cases and WI. The ratios of metastatic to non-metastatic cases of female genital system cancer (<it>r</it>²= 0.84, <it>p </it>= 0.0002), all-type cancers (<it>r</it>²= 0.73, <it>p </it>= 0.0017) and lung cancer (<it>r</it>²= 0.54, <it>p </it>= 0.0156) at diagnosis were positively correlated with WI.</p> <p>Conclusions</p> <p>The ratios of metastatic to non-metastatic cases of all-type, female genital system and lung cancers at diagnosis were statistically correlated with socioeconomic deprivation. Potential mediators for the correlation warrant further investigation in order to reduce health disparities associated with socioeconomic inequality.</p

Apical and basolateral localisation of GLUT2 transporters in human lung epithelial cells

Glucose concentrations of normal human airway surface liquid are ~12.5 times lower than blood glucose concentrations indicating that glucose uptake by epithelial cells may play a role in maintaining lung glucose homeostasis. We have therefore investigated potential glucose uptake mechanisms in non-polarised and polarised H441 human airway epithelial cells and bronchial biopsies. We detected mRNA and protein for glucose transporter type 2 (GLUT2) and glucose transporter type 4 (GLUT4) in non-polarised cells but GLUT4 was not detected in the plasma membrane. In polarised cells, GLUT2 protein was detected in both apical and basolateral membranes. Furthermore, GLUT2 protein was localised to epithelial cells of human bronchial mucosa biopsies. In non-polarised H441 cells, uptake of d-glucose and deoxyglucose was similar. Uptake of both was inhibited by phloretin indicating that glucose uptake was via GLUT-mediated transport. Phloretin-sensitive transport remained the predominant route for glucose uptake across apical and basolateral membranes of polarised cells and was maximal at 5–10 mM glucose. We could not conclusively demonstrate sodium/glucose transporter-mediated transport in non-polarised or polarised cells. Our study provides the first evidence that glucose transport in human airway epithelial cells in vitro and in vivo utilises GLUT2 transporters. We speculate that these transporters could contribute to glucose uptake/homeostasis in the human airway

Dynamic, Large-Scale Profiling of Transcription Factor Activity from Live Cells in 3D Culture

phenotypes. Taken together, our objective was to develop cellular arrays for dynamic, large-scale quantification of TF activity as cells organized into spherical structures within 3D culture.TF-specific and normalization reporter constructs were delivered in parallel to a cellular array containing a well-established breast cancer cell line cultured in Matrigel. Bioluminescence imaging provided a rapid, non-invasive, and sensitive method to quantify luciferase levels, and was applied repeatedly on each sample to monitor dynamic activity. Arrays measuring 28 TFs identified up to 19 active, with 13 factors changing significantly over time. Stimulation of cells with β-estradiol or activin A resulted in differential TF activity profiles evolving from initial stimulation of the ligand. Many TFs changed as expected based on previous reports, yet arrays were able to replicate these results in a single experiment. Additionally, arrays identified TFs that had not previously been linked with activin A.This system provides a method for large-scale, non-invasive, and dynamic quantification of signaling pathway activity as cells organize into structures. The arrays may find utility for investigating mechanisms regulating normal and abnormal tissue growth, biomaterial design, or as a platform for screening therapeutics

Influence of Psychological Factors on Pain and Disability in Anterior Knee Pain Patients

AKP patients express chronic pain but also disability. However, the correlation between pain and disability is not complete and linear. Some patients with a lot of pain show mild disability while others with much less pain also show great disability. The disability is profoundly influenced by other emotional and cognitive factors that are associated with the perception of pain. Therefore, the clinical efforts do not have to be focused only on treating the pain as a feeling but on identifying and modifying these factor

Methodology of calculation of construction and hydrodynamic parameters of a foam layer apparatus for mass-transfer processes

Промислова реалізація методу стабілізації газорідинного шару дозволяє значно розширити галузь застосування пінних апаратів і відкриває нові можливості інтенсифікації технологічних процесів з одночасним створенням маловідходних технологій. У статті встановлені основні параметри, що впливають на гідродинаміку пінних апаратів, розглянуті основні конструкції та режими роботи пінних апаратів. Виявлено зв'язок гідродинамічних параметрів. Розглянуто гідродинамічні закономірності пінного шару. Вказані фактори, що впливають на процес масообміну, як в газовій, так і в рідкій фазах. Проведений аналіз ряду досліджень показав, що перспективним напрямком інтенсифікації процесу масообміну є розробка апаратів з трифазним псевдозрідженим шаром зрошуваної насадки складних форм із сітчастих матеріалів. Отже, необхідне проведення спеціальних досліджень гідродинамічних режимів роботи апарату з сітчастою насадкою і визначенням параметрів, що впливають на швидкість переходу насадки з одного режиму в інший.Industrial implementation of the stabilization method of the gas-liquid layer can significantly expand the field of use of foaming apparatus and opens up new opportunities for intensifying technological processes with the simultaneous creation of low-waste technologies. The article establishes the basic parameters influencing the hydrodynamics of foam apparatus, considers the basic constructions and operating modes of foam apparatus. The connection of hydrodynamic parameters is revealed. The hydrodynamic laws of the foam layer are considered. The indicated factors affecting the process of mass transfer, both in the gas and in the liquid phases. The conducted analysis of a number of studies showed that the perspective direction of intensification of the mass transfer process is the development of apparatuses with a three-phase fluidized bed of an irrigated nozzle of complex forms with mesh materials