Quantitative Ultrasound Spectroscopic Imaging for Characterization of Disease Extent in Prostate Cancer Patients

Three-dimensional quantitative ultrasound spectroscopic imaging of prostate was investigated clinically for the noninvasive detection and extent characterization of disease in cancer patients and compared to whole-mount, whole-gland histopathology of radical prostatectomy specimens. Fifteen patients with prostate cancer underwent a volumetric transrectal ultrasound scan before radical prostatectomy. Conventional-frequency (~ 5 MHz) ultrasound images and radiofrequency data were collected from patients. Normalized power spectra were used as the basis of quantitative ultrasound spectroscopy. Specifically, color-coded parametric maps of 0-MHz intercept, midband fit, and spectral slope were computed and used to characterize prostate tissue in ultrasound images. Areas of cancer were identified in whole-mount histopathology specimens, and disease extent was correlated to that estimated from quantitative ultrasound parametric images. Midband fit and 0-MHz intercept parameters were found to be best associated with the presence of disease as located on histopathology whole-mount sections. Obtained results indicated a correlation between disease extent estimated noninvasively based on midband fit parametric images and that identified histopathologically on prostatectomy specimens, with an r² value of 0.71 (P < .0001). The 0-MHz intercept parameter demonstrated a lower level of correlation with histopathology. Spectral slope parametric maps offered no discrimination of disease. Multiple regression analysis produced a hybrid disease characterization model (r² = 0.764, P < .05), implying that the midband fit biomarker had the greatest correlation with the histopathologic extent of disease. This work demonstrates that quantitative ultrasound spectroscopic imaging can be used for detecting prostate cancer and characterizing disease extent noninvasively, with corresponding gross three-dimensional histopathologic correlation.     

TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4-a]pyrrolo[3,4-c]carbazole analogs

Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic and cellular biochemical assays; two orally bioavailable analogs were further profiled in functional assays and found to inhibit microvessel growth in rat aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs.     

Identification, characterization, and localization of a novel kidney polycystin-1-polycystin-2 complex

The functions of the two proteins defective in autosomal dominant polycystic kidney disease, polycystin-1 and polycystin-2, have not been fully clarified, but it has been hypothesized that they may heterodimerize to form a "polycystin complex" involved in cell adhesion. In this paper, we demonstrate for the first time the existence of a native polycystin complex in mouse kidney tubular cells transgenic for PKD1, non-transgenic kidney cells, and normal adult human kidney. Polycystin-1 is heavily N-glycosylated, and several glycosylated forms of polycystin-1 differing in their sensitivity to endoglycosidase H (Endo H) were found; in contrast, native polycystin-2 was fully Endo H-sensitive. Using highly specific antibodies to both proteins, we show that polycystin-2 associates selectively with two species of full-length polycystin-1, one Endo H-sensitive and the other Endo H-resistant; importantly, the latter could be further enriched in plasma membrane fractions and co-immunoprecipitated with polycystin-2. Finally, a subpopulation of this complex co-localized to the lateral cell borders of PKD1 transgenic kidney cells. These results demonstrate that polycystin-1 and polycystin-2 interact in vivo to form a stable heterodimeric complex and suggest that disruption of this complex is likely to be of primary relevance to the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease.     

Assessing population parameters and trends of Guiana dolphins (Sotalia guianensis): An eight‐year mark‐recapture study

This study represents the first attempt to study the population dynamics of Guiana dolphins (Sotalia guianensis), by evaluating a set of demographic parameters. The population of the Caravelas River estuary, eastern Brazil, was systematically monitored through a long‐term mark‐recapture experiment (2002–2009). Abundance estimates revealed a small population (57–124 dolphins), comprised of resident dolphins and individuals that temporarily leave or pass through the study area. Temporary emigration from the estuary to adjacencies (γ″= 0.33 ± 0.07 SE) and return rate (1 ?γ′= 0 .67) were moderate and constant, indicating that some dolphins use larger areas. Survival rate (?= 0.88 ± 0.07 SE) and abundance were constant throughout the study period. Power analysis showed that the current monitoring effort has high probability of detecting abrupt population declines (1 ?β= 0.9). Although the monitoring is not yet sensitive to subtle population trends, sufficient time to identify them is feasible (additional 3 yr). Despite such apparent stability, this population, as many others, inhabits waters exposed to multiple human‐related threats. Open and closed population modeling applied to photo‐identification data provide a robust baseline for estimating several demographic parameters and can be applied to other populations to allow further comparisons. Such synergistic efforts will allow a reliable definition of conservation status of this species.     

Brief inactivation of c-Myc is not sufficient for sustained regression of c-Myc-induced tumours of pancreatic islets and skin epidermis

Background  

Tumour regression observed in many conditional mouse models following oncogene inactivation provides the impetus to develop, and a platform to preclinically evaluate, novel therapeutics to inactivate specific oncogenes. Inactivating single oncogenes, such as c-Myc, can reverse even advanced tumours. Intriguingly, transient c-Myc inactivation proved sufficient for sustained osteosarcoma regression; the resulting osteocyte differentiation potentially explaining loss of c-Myc's oncogenic properties. But would this apply to other tumours?     

Taura syndrome virus (TSV) in Thailand and its relationship to TSV in China and the Americas

The cultivation of exotic Penaeus vannamei in Thailand began on a very limited scale in the late 1990s, but a Thai government ban on the cultivation of P. monodon in freshwater areas in 2000 led many Thai shrimp farmers to shift to cultivation of P. vannamei. Alarmed by the possibility of Taura syndrome virus (TSV) introduction, the Thai Department of Fisheries required that imported stocks of P. vannamei be certified free of TSV by RT-PCR (Reverse Trasciption Polymerase Chain Reaction) testing. During the interval of allowed importation, over 150,000 broodstock shrimp were imported, 67% of these from China and Taiwan. Despite the safeguards, TSV outbreaks occurred and we confirmed the first outbreak by RT-PCR in early 2003. This resulted in a governmental ban on all shrimp broodstock imports from February 2003, but TSV outbreaks have continued, possibly due to original introductions or to the continued illegal importation of stocks. To determine the origin of the TSV in Thailand, the viral coat protein gene VP1 was amplified by RT-PCR from several shrimp specimens found positive for TSV by RT-PCR from January to November 2003. These included 7 samples from P. vannamei disease outbreaks in Thailand, 3 other non-diseased shrimp samples from Thailand and Burma and 6 samples including P. vannamei and P. japonicus from China. Comparison revealed that the Thai, Burmese and Chinese TSV types formed a clade distinct from a clade of TSV types from the Americas.     

Highly branched polymers with polymyxin end groups responsive to Pseudomonas aeruginosa

Polymyxin peptide conjugated to the end groups of highly branched poly(N-isopropyl acrylamide) was shown to bind to a Gram negative bacterium, Pseudomonas aeruginosa . The nonbound polymer had a lower critical solution temperature (LCST) above 60 °C. However, binding caused aggregation, which was disrupted on cooling of the bacteria and polymer mixture. The data indicate that polymer binding of bacteria occurred by interaction of the end groups with lipopolysaccharide and that the binding decreased the LCST to below 37 °C. Cooling then progressed the polymer/bacteria aggregate through a bound LCST into an open polymer coil conformation that was not adhesive to P. aeruginosa .