Exploration of potential prognostic biomarkers in aflibercept plus FOLFIRI in Japanese patients with metastatic colorectal cancer

Aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (FOLFIRI) is a second‐line treatment for metastatic colorectal cancer. This ancillary exploratory analysis of data in Japanese people was aimed at exploring the relationship between a set of potential prognostic biomarkers and efficacy endpoints following aflibercept plus FOLFIRI therapy. Sixty‐two patients with metastatic colorectal cancer received aflibercept (4 mg/kg) plus FOLFIRI every 2 weeks. Seventy‐eight potential protein biomarkers were chosen for analysis based on their roles in angiogenesis, tumor progression, and tumor‐stroma interaction. Plasma levels of biomarkers at baseline and at pre‐dose 3 (day 1 of treatment cycle 3) were measured in all patients by ELISA. Relationships between these levels and efficacy endpoints were assessed. Ten potential biomarkers had a ±30% change from baseline to pre‐dose 3 (adjusted P < .001), with the greatest changes occurring in placental growth factor (median: +4716%) and vascular endothelial growth factor receptor 1 (+2171%). Baseline levels of eight potential biomarkers correlated with overall survival in a univariate Cox regression analysis: extracellular newly identified receptor for advanced glycation end‐products binding protein, insulin‐like growth factor‐binding protein 1, interleukin‐8, kallikrein 5, pulmonary surfactant‐associated protein D, tissue inhibitor of metalloproteinases 1, tenascin‐C, and tumor necrosis factor receptor 2. None correlated with progression‐free survival or maximum tumor shrinkage. Pre‐dose 3 levels did not correlate with any efficacy endpoints. Preliminary data show that these eight biomarkers could be associated with overall survival. ClinicalTrials.gov identifier: NCT01882868.     

Proteomic analysis of rat retina in a steroid-induced ocular hypertension model: Potential vulnerability to oxidative stress

Purpose To investigate global protein expression profiles in the retinas of normal and glucocorticoid-induced ocular hypertensive rats by proteomic analysis. Methods Ocular hypertension was induced by topical application of dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls. Intraocular pressure (IOP) was monitored by an electronic tonometer. Retinal protein expression profiling was carried out by two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Proteins were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Results In DEX-treated rats, average IOP was elevated significantly compared with controls. With DEX treatment, levels of four proteins were altered, as revealed by 2-D DIGE and MALDI-TOF mass spectrometry: apolipoprotein A1 (apoA1), a lipid-binding protein, upregulated 1.9-fold, P < 0.05; alpha A crystallin (CRYAA), a molecular chaperone, downregulated 2.7-fold, P < 0.01; superoxide dismutase 1 (SOD1), an antioxidant enzyme, downregulated 2.3-fold, P < 0.05; and triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, downregulated 2.3-fold, P < 0.01. Conclusions Downregulation of CRYAA, SOD1, and TPI1, observed here after a short period of DEX-induced ocular hypertension, may be involved in the onset of neural damage in steroid-induced glaucoma.     

Radiosensitive functional dye: clinical application for estimation of patient skin dose

Institutional review board approval and informed patient consent were obtained. The purpose of the study was to prospectively evaluate the use of radiosensitive indicators to estimate patient entrance skin dose (ESD). Forty-six patients wore a jacket with 48 or 52 indicators adhered to the back during percutaneous coronary interventions; they had eight additional indicators on their upper arms. The patients' ESDs were calculated according to the change in color of the indicators. There were good correlations between the ESDs estimated by using color measurements performed with an optical instrument and those estimated at visual observation (P < .001) and between the ESDs estimated by using a thermoluminescent dosimeter and those estimated by using color measurements (P < .001). The radiosensitive indicator method seems to be useful for estimating ESDs and their distribution during percutaneous coronary intervention; however, visual observation is reliable for estimating doses of up to 5 Gy only. (c) RSNA, 2006.     

Hyperleptinemia is associated with hypertension in Japanese males

Leptin is a hormone which is predominantly secreted by adipose tissue. Recent studies have shown that leptin increases arterial blood pressure. Although data from available animal studies clearly indicate an association between leptin and hypertension, results of human studies have been less definitive. We conducted a case-control study to examine the association between serum leptin levels and hypertension in 111 hypertensive subjects and 222 male controls, using conditional logistic regression analyses. Mean serum leptin levels were found to be marginally higher in the case subjects than in the control subjects (3.3 ng/ml versus 3.0 ng/ml), however, conditional logistic regression analysis revealed that subjects in the highest quartile had a significantly increased risk of hypertension compared with those in the lowest quartile, even after adjusting for drinking status and diabetes mellitus (adjusted OR, 2.11;95% CI, 1.01-4.39). Our findings suggest that leptin plays an important role in the development of hypertension.     

Identical rearrangement of NSP3 genes found in three independently isolated virus clones derived from mixed infection and multiple passages of Rotaviruses

Three rotavirus variants with a rearranged RNA segment derived from the NSP3 gene were isolated in three independent experiments of coinfection and multiple passages of simian rotavirus strain SA11 and single-VP7-gene- or NSP1-gene-substitution reassortants having genetic background of SA11. Sequence analysis indicated that the three rearranged NSP3 genes had almost identical sequences and genomic structures organized by partial duplication of the open reading frame in a head-to-tail orientation following the termination codon. The junction site of the original NSP3 gene (first copy) and the duplicated portion (second copy) was identical among the three rearranged genes, while a direct repeat, i.e., a homologous sequence between the first copy and second template for duplication, typically located at the junction site, was not detected. However, short similar sequences were present at the end of the first copy and beginning of the second copy. These findings suggest that rearrangement of the NSP3 gene may occur at a certain preferential site which is related to sequence similarity between 3′-untranslated region and a region near the 5′-end of ORF.