Association of Diffusion and Anatomic Imaging Parameters with Survival for Patients with Newly Diagnosed Glioblastoma Participating in Two Different Clinical Trials

PURPOSE: To evaluate the time course and association with survival of anatomic lesion volumes and diffusion imaging parameters for patients with newly diagnosed glioblastoma who were treated with radiation and concurrently with either temozolomide and enzastaurin (TMZ+enza cohort) or temozolomide, erlotonib, and bevaciumab (TMZ+erl+bev cohort). MATERIALS AND METHODS: Regions of interest corresponding to the contrast-enhancing and hyperintense lesions on T2-weighted images were generated. Diffusion-weighted images were processed to provide maps of apparent diffusion coefficient, fractional anisotropy, and longitudinal and radial eigenvalues. Histograms of diffusion values were generated and summary statistics calculated. Cox proportional hazards models were employed to assess the association of representative imaging parameters with survival with adjustments for age, Karnofsky performance status, and extent of resection. RESULTS: Although progression-free survival was significantly longer for the TMZ+erl+bev cohort (12.8 vs 7.3 months), there was no significant difference in overall survival between the two populations (17.0 vs 17.8 months). The median contrast-enhancing lesion volumes decreased from 6.3 to 1.9 cm³ from baseline to the postradiotherapy scan for patients in the TMZ+enza cohort and from 2.8 to 0.9cm³ for the TMZ+erl+bev cohort. Changes in the T2 lesion volumes were only significant for the latter cohort (26.5 to 11.9 cm³). The median apparent diffusion coefficient and related diffusion parameters were significantly increased for the TMZ+enza cohort (1054 to 1225 μm²/s). More of the anatomic parameters were associated with survival for the TMZ+enza cohort, whereas more diffusion parameters were associated with survival for the TMZ+erl+bev cohort. CONCLUSION: The early changes in anatomic and diffusion imaging parameters and their association with survival reflected differences in the mechanisms of action of the treatments that were being given. This suggests that integrating diffusion metrics and anatomic lesion volumes into the Response Assessment in Neuro-Oncology criteria would assist in interpreting treatment-induced changes and predicting outcome in patients with newly diagnosed glioblastoma who are receiving such combination treatments.     

Quercetin plays protective role in oxidative induced apoptotic events during chronic chlorpyrifos exposure to rats

Chlorpyrifos (CPF), an organophosphate insecticide has a wider application throughout the world to protect agricultural crops and vegetables from insects. Polyphenolic compounds are considered as beneficial against toxicities induced by organophosphates. The present study was conducted to understand the neuroprotective role of quercetin in chlorpyrifos‐induced apoptotic events in rats. Twenty‐four male Sprague Dawley rats weighing 170 to 200 g were divided into four groups viz: Control, chlorpyrifos treated (13.5 mg/kg body wt. alternate day), quercetin treated (50 mg/kg body wt. every day) and combined chlorpyrifos + quercetin treated. All the treatments were carried out for a total duration of 60 days. Protein carbonyl content and acetylcholinesterase activity were estimated in serum along with cerebrum and cerebellum to ascertain neurotoxicity. Further, for appraisal of neurodegeneration as a consequence of apoptosis, protein expressions of Bcl‐2, Bax, cytochrome c, caspase‐8, and caspase‐9 were assessed. The results showed that protein carbonyl contents were markedly increased in both serum and brain tissues (cerebrum and cerebellum) of chlorpyrifos‐treated rats when compared with control group and were appreciably improved upon simultaneous supplementation with quercetin. Further, chlorpyrifos treatment revealed a significant decrease in the enzyme activity of acetylcholinesterase in serum as well as in cerebrum and cerebellum, which however was increased upon concomitant treatment with quercetin. In chlorpyrifos‐treated animals, we have observed a significant decrease in the protein expression level of Bcl‐2, but a remarkable increase in the expression levels of Bax, cytochrome c, caspase‐8, and caspase‐9 in both cerebrum and cerebellum. Interestingly, when chlorpyrifos‐treated animals were supplemented with quercetin, a significant increase in the expression of Bcl‐2 and an appreciable decline in the expression levels of Bax, cytochrome c, caspase‐8, and caspase‐9 was observed. In conclusion, the present study advocates that quercetin may prove to be a useful candidate in containing the oxidative‐induced apoptotic events during chlorpyrifos exposure.     

Combined action of lead and lithium on essential and nonessential elements in rat blood

The effects of lead and lithium ingestion, separately and in combination, on the levels of K, Fe, Cu, Zn, Br, Rb, and As in rat blood were studied by the Energy Dispersive X-ray Fluorescence technique. Two different doses of lead acetate, i.e., 50 and 100 mg/Kg body wt (low and high doses), were administered orally to rats, daily, for 1 and 4 months (short and long terms), whereas lithium in the form of lithium carbonate was given to rats in food (1.1 g/kg diet) for 1 and 4 mo separately, and also to rats receiving lower and higher doses of lead. K levels were found to be depressed significantly with lead treatment, whereas Fe contents were enhanced marginally after 1 mo of treatment when only the higher dose of lead was given. As, Br, and Rb contents were found to be elevated following lead treatment for short and long terms at both the dose levels. However, Cu contents were lowered, whereas Zn contents were raised only after long term treatment with lead. The Fe, Cu, As, and Br contents remained unaltered, whereas K, Rb, and Zn contents were reduced significantly when lithium was administered for short term. Moreover, Cu and Fe levels were also found to be reduced and Br contents were enhanced only after long term treatment. During the combined treatment with lead and lithium for short and long terms, the levels of K, As, and Rb were observed to decrease, whereas Fe contents were enhanced when estimated for both doses of lead. On the contrary, Cu levels were lowered only with the higher dose of lead acetate when given in combination with lithium for 1 and 4 mo. Br contents were only effectively decreased after 4 mo of treatment.     

Purification and Characterization of Protease Inhibitor from Rice Bean (Vigna umbellata T.) Seeds

A Protease inhibitor from seeds of rice bean has been purified to apparent homogeneity as judged by native-PAGE with about 29% recovery using ammonium sulfate fractionation, ion exchange chromatography on DEAE-cellulose, and gel filtration through Sephadex G-100. The purified preparation with molecular weight of 16.8 kD was found to be a monomer as revealed by SDS-PAGE under reducing and non-reducing conditions. The purified inhibitor in solution was stable upto 40°C. However, it lost its activity gradually and was completely inactive when heated at 100°C for 2 h and 125°C for 1 h. Heating at 125°C changed the conformation of the inhibitor as was evident from the altered UV spectrum compared to that of native. It had two pH optima at pH 6.0 and at 10.0 and was stable over a wide range of pH (pH 3.0 to 10.0). It lost its activity on exposure to 2-mercaptoethanol, indicating the role of S-S linkages in maintaining the three dimensional structure of the protein inhibitor. The inhibitor was completely inactive towards papain, while it inhibited pepsin only slightly. Trypsin and chymotrypsin were inhibited upto the extent of 60% and 30%, respectively. Trypsin inhibition was of non-competitive type with dissociation constant for the enzyme-inhibitor complex in the region of 2.07 mg ml^-1. The rice bean inhibitor appears to be of Bowman-Birk type as it has molecular weight lower than that generally observed for Kunitz type inhibitors and seems to be double headed - a characteristic specific of Bowman - Birk type inhibitor.     

Interplay between p53 and non-coding RNAs in the regulation of EMT in breast cancer

The epithelial–mesenchymal transition (EMT) plays a pivotal role in the differentiation of vertebrates and is critically important in tumorigenesis. Using this evolutionarily conserved mechanism, cancer cells become drug-resistant and acquire the ability to escape the cytotoxic effect of anti-cancer drugs. In addition, these cells gain invasive features and increased mobility thereby promoting metastases. In this respect, the process of EMT is critical for dissemination of solid tumors including breast cancer. It has been shown that miRNAs are instrumental for the regulation of EMT, where they play both positive and negative roles often as a part of a feed-back loop. Recent studies have highlighted a novel association of p53 and EMT where the mutation status of p53 is critically important for the outcome of this process. Interestingly, p53 has been shown to mediate its effects via the miRNA-dependent mechanism that targets master-regulators of EMT, such as Zeb1/2, Snail, Slug, and Twist1. This regulation often involves interactions of miRNAs with lncRNAs. In this review, we present a detailed overview of miRNA/lncRNA-dependent mechanisms that control interplay between p53 and master-regulators of EMT and their importance for breast cancer.Subject terms: Breast cancer, Long non-coding RNAs, miRNAs     

Assessment of Genetic Diversity,Micromorphology and Antimicrobial Activity in Nepeta cataria L.

The mosquito repellent Nepetalactone rich Nepeta cataria L. (catmint) plant has a variety of therapeutic and industrial potential. Reports on the genetic diversity of N. cataria germplasm are minimal globally and need attention for adding a new variety into commercial cultivation. The present study, therefore, assessed the genetic diversity among thirteen half-sib genotypes of N. cataria using agro economic and phytochemical traits. The experimental set has shown substantial variation for agro economic traits studied. Among all the studied populations, fresh herb-based essential oil content ranged from 0.1 % to 0.3 %, with a grand mean of 1.67 %. However, the estimated oil yield ranged from 44.4 kg/h to 120.73 kg/h with an average of 71.34 kg/h. Among the eleven phytochemical constituents detected in different concentrations in the essential oil of experimental sets, 4aα,7α,7aα-Nepetalactone (67.9–87.5 %) constituted the significant proportion of essential oil. Altogether, based on mean comparison, the population NC8 was found to be promising for estimated oil yield and 4aα,7α,7aα-Nepetalactone content. The greater heritability estimates (h²bs) and genetic advance as percent of mean (GAM) were observed for important economic parameters, i. e., oil content, herb yield, and oil yield. The cluster analysis revealed the least interactions between various agro economic and phytochemical variables. The microscopic study of trichome showed a positive correlation of abaxial leaf surface with essential oil content. The promising antimicrobial potential of catmint oil was also observed against human health-related pathogens. The results infer from our study provide valuable insight for genetic improvement and product development in the catmint germplasm.     

Speciation and Vertical Distribution of Lead and Lead Shot in Soil at a Recreational Firing Range

In this study, the speciation, vertical distribution and soil particle size fractions of lead in soil samples at a recreational firing range was determined. This study was performed to gain a better understanding of how lead shot breaks down at ranges. Both the chemical form of lead and the types of soil particles with which lead is associated are important for understanding not only the mobility and persistence, but also the human and ecological impact of lead at these ranges. Lead as shot gun pellets was found to be the dominant form of lead in soil samples. The highest levels were measured in surface samples located in the “fall zone” of the range. Results indicate shot to be relatively absent below surficial samples. Lead concentrations in soil decreased markedly across a 0–6″ depth profile. Lead carbonates were the dominant non-shot form of lead present at all depths. Water-soluble lead species made up a minor fraction of the non-shot lead present in the samples. Based on soil particle sizes measured, highest concentrations of lead were measured in soil particles passing a 0.075 mm sieve.