Efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma: post hoc analysis of a randomized clinical trial.

BACKGROUND: Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. METHODS: The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this post hoc analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. RESULTS: A total of 108 patients had sarcomatoid histology and were included in this post hoc analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. CONCLUSIONS: In this subgroup analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.

Effect of tissue frozen on quantitative optical properties using optical coherence tomography.

The purpose is to demonstrate the optical charactering concerning nasopharyngeal tissue of pig by fresh sections and frozen correlating sections with optical coherence tomography (OCT). After being imaged on a fresh specimen, samples are then stored in low temperature refrigerators (-80°C) for one year for the second OCT measurement. The OCT structure of the epithelium, lamina propria, and the basement membrane are still resolvable; the median scattering coefficients and anisotropy factors fitting from OCT images based on the multiple scattering effects for epithelium are 27.6 mm-1 [interquartile range (IQR) 23.6 to 29.3 mm-1] versus 22.5 mm-1 (IQR 20.5 to 24.4 mm-1), 0.86 (IQR 0.81 to 0.9) versus 0.88 (IQR 0.87 to 0.9) for fresh and frozen tissue, respectively; and 10.2 mm-1 (IQR 8.1 to 13.6 mm-1) versus 9.6 mm-1 (IQR 8.1 to 13.8 mm-1), 0.96 (IQR 0.93 to 0.98) versus 0.92 (IQR 0.9 to 0.98) for lamina propria, respectively. The results show that the frozen storage method can be used for OCT research.

The structure and roles of sterile flowers in Viburnum macrocephalum f. keteleeri (Adoxaceae).

The formation and ecological roles of sterile flowers in flowering plants are interesting issues in floral biology and evolution. Here, we investigated the morphological and anatomical characteristics of both fertile and sterile flowers of Viburnum macrocephalum f. keteleeri, a self-incompatible and insect-pollinated shrub, during different developmental stages of flowers. In addition, pollinator visitation rates and fruit set were determined in intact inflorescences and those with sterile flowers removed. The results indicate that sterile and fertile flowers were developmentally similar during early developmental stages, and that development of the flower types diverged about 15 days before flowering. In addition, pollinator visitation rates, number of pollen grains on stigmas and fruit set were significantly higher in inflorescences with sterile flowers than those without sterile flowers. The results suggest that sterile flowers of this species evolved from fertile flowers under long-term selective pressure, and play a crucial role in enhancing reproductive success through effectively attracting pollinators to the plant and thus enhancing fruit set.

Screening, cloning and overexpression of Aspergillus niger phytase (phyA) in Pichia pastoris with favourable characteristics.

AIMS: Using gene cloning and overexpression to obtain a potential industrial phytase as a feed additive to upgrade the nutritional quality of phytate-rich seed-based animal feed. METHODS AND RESULTS: A phyA gene from a high extracellular phytase-producing Aspergillus niger sp. was cloned and overexpressed in Pichia pastoris GS115 using the secretive expression vector pPICZalphaA. After cultivation for 4 days in buffered methanol complex medium (BMMY) containing methanol for induction, catalytically active phytase was secreted as a predominantly extracellular protein. The activity of the expressed phytase in fermented broth was 30 000-fold higher than that of native phytase with a specific activity of 503 U mg(-1). The Lineweaver-Burk plot indicated K(m) values of 0.196 mmol l(-1) for sodium phytate and 18.16 mmol l(-1) for p-nitrophenylphosphate (pNPP). Thermostability studies showed that recombinant phytase retained 70% activity after exposure to 90 degrees C for 5 min and 65% activity after 30 min, much higher than for commercial phytase. CONCLUSIONS: The higher activity and high thermostability of recombinant phytase enable it to withstand the temperatures of the feed pelleting process. SIGNIFICANCE AND IMPACT OF THE STUDY: The characteristics of this recombinant phytase, especially the good thermostability, are likely to render it of potential industrial importance.

Plant regeneration from in vitro-cultured seedling leaf protoplasts of Actinidia eriantha Benth.

Newly expanded in vitro leaves of Actinidia eriantha were used for protoplast isolation. Protoplasts were cultured in liquid MS medium (lacking NH4NO3) supplemented with 2,4-D (2,4-dichlorophenoxyacetic acid) and 0.4 M glucose. The plating efficiency after 3 weeks of culture was 19.4%, and calli were recovered without addition of fresh medium. These calli regenerated shoots on transfer to MS medium containing 2.28 µM zeatin and 0.57 µM IAA (indole-3-acetic acid). Regenerated shoots were rooted by immersion in 20 ppm IBA (indole-3-butyric acid) solution before culturing on half-strength MS medium lacking growth regulators. Somaclonal variation, in terms of chromosome number and nuclei per cell of protoplast-derived plants, was estimated.

[Effect of expression of exogenous PDGF-A chain on growth and transformation of CHO cells].

CHO cells were transfected with plasmid pSV2-PDGF-A (containing human PDGF-A cDNA) by calcium phosphate method. Twenty transfected cell lines were obtained after G418 selection. The selected 2 cell lines At1 and Aot7), with prominent changes in morphology and growth behaviour, showed transcription of PDGF-A chain mRNA much higher than CHO cells, strong fluorescent PDGF-specific reaction, appearing that PDGF-like proteins were synthesized in cytoplasm of these cells. At1 and Aot7 cells not only had increased growth rate, but also formed large colonies in soft agar and grew into fibrosarcomas in nude mice. These results suggested that the expression of exogenous PDGF-A gene might cause the uncontrolled growth and malignant transformation of CHO cells.

[Expression of exogenous platelet-derived growth factor B chain gene in CHO cells].

CHO cells were transfected with plasmid pSM-1 (containing human c-sis cDNA) singly or co-transfected with pSV 2 neo DNA by calcium phosphate method. After low serum or G418 selection several cell lines with expression of platelet-derived growth factor (PDGF) were obtained. One among them, FB5, was of the highest PDGF expression and showed the following biological characteristics when compared with CHO cells: (1) a prominent change in morphology from spindle to round in shape: (2) increase of growth rate; (3) growth in low serum (2%) medium as a semisuspension culture; (4) growth on soft agar to larger colonies; (5) synthesis of PDGF in cytoplasm identified by immunofluorescent method; (6) the conditioned medium stimulated DNA synthesis of NRK cells; (7) RNA dot hybridization showing high transcription of PDGF mRNA; (8) southern blot showing integration of human c-sis gene was still stable after 7 months. These results indicated that intergration of exogenous c-sis gene and its high expression might cause CHO cells to high growth rate and even transformation. The establishment of this stable transformed cell line, FB5 is thought to be a good model for further study on the function of PDGF in cell growth control and cell transformation.