NaPi2b expression in a large surgical Non-Small Cell Lung Cancer (NSCLC) cohort.

BACKGROUND: NaPi2b is a multi-transmembrane sodium-dependent phosphate transporter expressed at normal levels in several organs, including lung. High expression levels have been reported in various tumors including breast, thyroid, ovarian and non-small cell lung cancer. To date evaluation of NaPi2b expression has mostly been restricted to smaller lung cancer cohorts. METHODS: Analyses were performed on archival formalin fixed paraffin embedded primary tumor specimens from patients who had undergone curative intent resection at an Australian tertiary hospital. Tissue microarrays were constructed and stained with the chimeric anti-NaPi2b antibody, MERS67. Semi-quantitative H-scores (range 0 - 300) were calculated for each core tissue sample (H-score = % tumor cells staining for NaPi2b multiplied by staining intensity). An overall average H-score was reported for each specimen, with a cut-off score of 50 considered positive. RESULTS: Of 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137 of 208 (65.9%) adenocarcinoma cases, and 5 of 179 (2.8%) squamous cases (P < .0001). High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, and TTF1 positivity (adenocarcinoma cases only). High NaPi2b expression was associated with improved overall survival (median 54 vs. 35 months, P = .029). CONCLUSION: High NaPi2b expression was noted in a significant subset of adenocarcinoma cases, and in particular amongst those who were TTF1+, or exhibited EGFR or KRAS mutations. This agrees with earlier reports and highlights the significance that NaPi2b may have a role as a possible target for delivery of cytotoxic agents via antibody-drug conjugate models for some patients with lung adenocarcinoma.

Elastic wave propagation in smooth and wrinkled stratified polymer films.

Periodic materials with sub-micrometer characteristic length scale can provide means for control of propagation of hypersonic phonons. In addition to propagation stopbands for the acoustic phonons, distinct dispersive modes can reveal specific thermal and mechanical behavior under confinement. Here, we employ both experimental and theoretical methods to characterize the phonon dispersion relation (frequency versus wave vector). We employed Brillouin light scattering (BLS) spectroscopy to record the phonon dispersion in stratified multilayer polymer films. These films consist of 4-128 alternate polycarbonate (PC) and poly (methyl methacrylate) (PMMA) layers along and normal to the periodicity direction. The distinct direction-dependent phonon propagation was theoretically accounted for, by considering the polarization, frequency and intensity of the observed modes in the BLS spectra. Layer-guiding was also supported by the glass transition temperatures of the PC and PMMA layers. The number of phonon dispersion branches increased with the number of layers but only a few branches were observable by BLS. Introduction of an additional in-plane periodicity, through a permanent wrinkling of the smooth PC/PMMA films, had only subtle consequences in the phonon propagation. Using the frequencies of the periodicity induced modes and momentum conservation equation we were able to precisely back calculate the wrinkle periodicity. However, a wrinkling-induced acoustic stopband utilizing flexible layered materials is still a challenge.

Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer.

BACKGROUND: Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects. METHODS: We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population. RESULTS: Patients with low expression of VEGF-D (0, 1þ) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CBþCBM), 0.21; 95% CI, 0.08­0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13­0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2þ PFS HR, 0.67; 95% CI, 0.45­1.00; OS HR, 0.82; 95% CI, 0.52­1.30; VEGF-D 3þ PFS HR, 0.77; 95% CI, 0.50­1.17; OS HR, 1.28; 95% CI, 0.79­2.09) (P interaction o0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression. CONCLUSIONS: The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.