Intratumor C-reactive protein as a biomarker of prognosis in localized renal cell carcinoma.

PURPOSE: Serum C-reactive protein has been shown to have prognostic value in localized and metastatic renal cell carcinoma. However, the prognostic value of intratumor C-reactive protein remains unknown. MATERIALS AND METHODS: A total of 95 patients with resected, clinically localized (T1-T4N0M0) clear cell renal cell carcinoma were followed postoperatively. Intratumor C-reactive protein expression was assessed in surgical specimens using immunohistochemical analysis. Patients were categorized by staining intensity into low risk (staining 0 to 1), intermediate risk (staining 2) and high risk (staining 3) groups. Kaplan-Meier and multivariate Cox regression analyses were used to examine overall survival across patient and disease characteristics. Variables examined in multivariate Cox regression analysis included T stage, Fuhrman nuclear grade, tumor size, preoperative serum C-reactive protein and intratumor C-reactive protein staining. RESULTS: Followup extended up to 46 months with a mean (SD) of 29.8 (11.0) months. Twelve patients (12.6%) died during followup. Of all tumors 49.5%, 25.3% and 25.3% were graded by intratumor C-reactive protein staining as low risk (0 to 1), intermediate risk (2) and high risk (3), respectively. After controlling for variables significant on univariate analysis, patients in the high risk (3) group experienced a 27-fold increased risk of overall mortality compared to those in the low risk (0-1) group (HR 27.767, 95% CI 1.488-518.182). After adjusting for tumor staining, preoperative serum C-reactive protein was not a significant predictor of overall survival (p = 0.741). CONCLUSIONS: Intratumor C-reactive protein may be a robust biomarker of prognosis in patients with localized renal cell carcinoma.

Postoperative better than preoperative C-reactive protein at predicting outcome after potentially curative nephrectomy for renal cell carcinoma.

OBJECTIVES: Preoperative C-reactive protein (CRP) predicts metastasis and mortality in localized renal cell carcinoma (RCC). However, the predictive potential of after resection of localized RCC remains unclear. Therefore, we assessed the absolute ability of postoperative CRP to predict metastases and mortality as a continuous variable. METHODS: Patients with clinically localized (T1-T3N0M0) clear-cell RCC were followed for 1 year postoperatively. Metastases were identified radiologically and mortality by death certificate. Univariate and multivariate binary logistic regression analyses examined 1 year relapse-free survival (RFS) and overall survival (OS) across patient and disease characteristics. RESULTS: Of the 110 patients in this study, 16.4% developed metastases and 6.4% died. Mean (SD) postoperative CRP for patients who did and did not develop metastases were 69.06 (73.55) mg/L and 5.27 (7.80), respectively. Mean (SD) postoperative CRP for patients who did and did not die were 89.31 (69.51) mg/L and 10.88 (30.32), respectively. In multivariate analysis, T-stage (OR: 12.452, 95% CI: 2.889-53.660) and postoperative CRP ((B: .080, SE: .025; P < .001) were significant predictors of RFS. T-Stage (OR: 11.715; 95% CI: 1.102-124.519) and postoperative CRP (B: .017; SE: .007; P < .001) were also significant predictors of OS. After adjusting for postoperative CRP, preoperative CRP was not predictive of these outcomes. CONCLUSIONS: Postoperative, not preoperative, CRP is the better predictor of metastasis and mortality following nephrectomy for localized RCC. Clinicians should consider absolute postoperative CRP to identify high-risk patients for closer surveillance or additional therapy. Predictive algorithms should consider incorporating postoperative CRP as a continuous variable to maximize predictive ability.

Absolute preoperative C-reactive protein predicts metastasis and mortality in the first year following potentially curative nephrectomy for clear cell renal cell carcinoma.

PURPOSE: C-reactive protein is an inflammatory biomarker associated with tumor burden and metastasis in renal cell carcinoma. Recent studies suggest that preoperative C-reactive protein predicts metastasis and mortality after nephrectomy for localized renal cell carcinoma. However, these studies dichotomized C-reactive protein (typically 10 mg/l or greater vs less than 10 mg/l). Considering the continuous range of C-reactive protein (less than 1 mg/l to greater than 100 mg/l) we assessed the ability of absolute preoperative C-reactive protein to predict metastases and mortality as a continuous variable. MATERIALS AND METHODS: Patients with clinically localized (T1-T3N0M0) clear cell renal cell carcinoma were followed for 1 year postoperatively. Metastases were identified radiologically and mortality was determined by death certificate. Univariate and multivariate binary logistic regression analyses examined 1-year relapse-free survival and overall relative survival across patient and disease characteristics. RESULTS: Of the 130 patients in this study metastases developed in 24.6% and 10.8% of the patients died. Mean (SD) preoperative C-reactive protein for patients in whom metastases did and did not develop was 89.17 (74.17) and 9.16 (30.62) mg/l, respectively. Mean preoperative C-reactive protein for patients who did and did not die was 102.61 (77.32) and 19.52 (46.10) mg/l, respectively. On multivariate analysis SSIGN score (p <0.001) and preoperative C-reactive protein (B 0.027, SE 0.003, p <0.001) were significant predictors of relapse-free survival, and preoperative platelets (p = 0.009) and preoperative C-reactive protein (B 0.011, SE 0.008, p <0.001) were significant predictors of overall relative survival. CONCLUSIONS: Absolute preoperative C-reactive protein is a robust predictor of metastasis and mortality after nephrectomy for localized renal cell carcinoma. Clinicians should consider absolute preoperative C-reactive protein to identify high risk patients for closer surveillance or additional therapy. In addition, predictive algorithms and models of metastasis should consider incorporating C-reactive protein as a continuous variable to maximize predictive ability.

Transplantation prospects for the inner retina.

Transplantation of stem or progenitor cells is an attractive new approach for treating neurodegenerative conditions of the central nervous system, which aims to protect or replace neurons and improve function. Proof of principle has already been shown in the retina that photoreceptors may be replaced by transplantation of neural progenitor cells. However, the task of retinal ganglion cell replacement is much more complex, as new cells will need to establish complex connections within the retina and also extend axons to precise targets in the brain. Although progress has been made in this field, it is likely that neuroprotective clinical applications will be established more quickly. Our laboratory has focused on the intraocular transplantation of cells to treat inner retinal disease, either by neuronal replacement or neuroprotection of existing cells. We have investigated the efficacy and effects of transplanting a variety of cell types, including human Müller stem cells (MIO-M1), oligodendrocyte precursor cells (OPCs), and bone marrow-derived mesenchymal stromal cells (MSCs) in a rat model of experimentally induced glaucoma. We also have developed and characterized a novel in vitro organotypic retinal explant culture system for exploring the methods of enhancing the efficacy of cell transplantation for the inner retina. In this review, we discuss the potentially beneficial effects of intraocular cell injections, identify current shortcomings of retinal stem cell therapy, and suggest directions for future research.

Stem cells for neuroprotection in glaucoma.

Stem cell transplantation is currently being explored as a therapy for many neurodegenerative diseases including glaucoma. Cellular therapies have the potential to provide chronic neuroprotection after a single treatment, and early results have been encouraging in models of spinal cord injury and Parkinson's disease. Stem cells may prove ideal for use in such treatments as they can accumulate at sites of injury in the central nervous system (CNS) and may also offer the possibility of targeted treatment delivery. Numerous stem cell sources exist, with embryonic and fetal stem cells liable to be superseded by adult-derived cells as techniques to modify the potency and differentiation of somatic cells improve. Possible neuroprotective mechanisms offered by stem cell transplantation include the supply of neurotrophic factors and the modulation of matrix metalloproteinases and other components of the CNS environment to facilitate endogenous repair. Though formidable challenges remain, stem cell transplantation remains a promising therapeutic approach in glaucoma. In addition, such studies may also provide important insights relevant to other neurodegenerative diseases.

Hyperion's sponge-like appearance.

Hyperion is Saturn's largest known irregularly shaped satellite and the only moon observed to undergo chaotic rotation. Previous work has identified Hyperion's surface as distinct from other small icy objects but left the causes unsettled. Here we report high-resolution images that reveal a unique sponge-like appearance at scales of a few kilometres. Mapping shows a high surface density of relatively well-preserved craters two to ten kilometres across. We have also determined Hyperion's size and mass, and calculated the mean density as 544 +/- 50 kg m(-3), which indicates a porosity of >40 per cent. The high porosity may enhance preservation of craters by minimizing the amount of ejecta produced or retained, and accordingly may be the crucial factor in crafting this unusual surface.

Cassini observes the active south pole of Enceladus.

Cassini has identified a geologically active province at the south pole of Saturn's moon Enceladus. In images acquired by the Imaging Science Subsystem (ISS), this region is circumscribed by a chain of folded ridges and troughs at approximately 55 degrees S latitude. The terrain southward of this boundary is distinguished by its albedo and color contrasts, elevated temperatures, extreme geologic youth, and narrow tectonic rifts that exhibit coarse-grained ice and coincide with the hottest temperatures measured in the region. Jets of fine icy particles that supply Saturn's E ring emanate from this province, carried aloft by water vapor probably venting from subsurface reservoirs of liquid water. The shape of Enceladus suggests a possible intense heating epoch in the past by capture into a 1:4 secondary spin/orbit resonance.

Cassini Imaging Science: initial results on Saturn's rings and small satellites.

Images acquired of Saturn's rings and small moons by the Cassini Imaging Science Subsystem (ISS) during the first 9 months of Cassini operations at Saturn have produced many new findings. These include new saturnian moons; refined orbits of new and previously known moons; narrow diffuse rings in the F-ring region and embedded in gaps within the main rings; exceptionally fine-scale ring structure in moderate- to high-optical depth regions; new estimates for the masses of ring-region moons, as well as ring particle properties in the Cassini division, derived from the analysis of linear density waves; ring particle albedos in select ring regions; and never-before-seen phenomena within the rings.

Cassini Imaging Science: initial results on Phoebe and Iapetus.

The Cassini Imaging Science Subsystem acquired high-resolution imaging data on the outer Saturnian moon, Phoebe, during Cassini's close flyby on 11 June 2004 and on Iapetus during a flyby on 31 December 2004. Phoebe has a heavily cratered and ancient surface, shows evidence of ice near the surface, has distinct layering of different materials, and has a mean density that is indicative of an ice-rock mixture. Iapetus's dark leading side (Cassini Regio) is ancient, heavily cratered terrain bisected by an equatorial ridge system that reaches 20 kilometers relief. Local albedo variations within and bordering Cassini Regio suggest mass wasting of ballistically deposited material, the origin of which remains unknown.

Cassini Imaging Science: initial results on Saturn's atmosphere.

The Cassini Imaging Science Subsystem (ISS) began observing Saturn in early February 2004. From analysis of cloud motions through early October 2004, we report vertical wind shear in Saturn's equatorial jet and a maximum wind speed of approximately 375 meters per second, a value that differs from both Hubble Space Telescope and Voyager values. We also report a particularly active narrow southern mid-latitude region in which dark ovals are observed both to merge with each other and to arise from the eruptions of large, bright storms. Bright storm eruptions are correlated with Saturn's electrostatic discharges, which are thought to originate from lightning.

Galileo at Io: results from high-resolution imaging.

During late 1999/early 2000, the solid state imaging experiment on the Galileo spacecraft returned more than 100 high-resolution (5 to 500 meters per pixel) images of volcanically active Io. We observed an active lava lake, an active curtain of lava, active lava flows, calderas, mountains, plateaus, and plains. Several of the sulfur dioxide-rich plumes are erupting from distal flows, rather than from the source of silicate lava (caldera or fissure, often with red pyroclastic deposits). Most of the active flows in equatorial regions are being emplaced slowly beneath insulated crust, but rapidly emplaced channelized flows are also found at all latitudes. There is no evidence for high-viscosity lava, but some bright flows may consist of sulfur rather than mafic silicates. The mountains, plateaus, and calderas are strongly influenced by tectonics and gravitational collapse. Sapping channels and scarps suggest that many portions of the upper approximately 1 kilometer are rich in volatiles.

Galileo imaging of atmospheric emissions from Io.

The Galileo spacecraft has detected diffuse optical emissions from Io in high-resolution images acquired while the satellite was eclipsed by Jupiter. Three distinct components make up Io's visible emissions. Bright blue glows of more than 300 kilorayleighs emanate from volcanic plumes, probably due to electron impact on molecular sulfur dioxide. Weaker red emissions, possibly due to atomic oxygen, are seen along the limbs, brighter on the pole closest to the plasma torus. A faint green glow appears concentrated on the night side of Io, possibly produced by atomic sodium. Io's disk-averaged emission diminishes with time after entering eclipse, whereas the localized blue glows brighten instead.

High-temperature silicate volcanism on Jupiter's moon Io.

Infrared wavelength observations of Io by the Galileo spacecraft show that at least 12 different vents are erupting lavas that are probably hotter than the highest temperature basaltic eruptions on Earth today. In at least one case, the eruption near Pillan Patera, two independent instruments on Galileo show that the lava temperature must have exceeded 1700 kelvin and may have reached 2000 kelvin. The most likely explanation is that these lavas are ultramafic (magnesium-rich) silicates, and this idea is supported by the tentative identification of magnesium-rich orthopyroxene in lava flows associated with these high-temperature hot spots.

Salts on Europa's surface detected by Galileo's near infrared mapping spectrometer. The NIMS Team.

Reflectance spectra in the 1- to 2.5-micrometer wavelength region of the surface of Europa obtained by Galileo's Near Infrared Mapping Spectrometer exhibit distorted water absorption bands that indicate the presence of hydrated minerals. The laboratory spectra of hydrated salt minerals such as magnesium sulfates and sodium carbonates and mixtures of these minerals provide a close match to the Europa spectra. The distorted bands are only observed in the optically darker areas of Europa, including the lineaments, and may represent evaporite deposits formed by water, rich in dissolved salts, reaching the surface from a water-rich layer underlying an ice crust.

Evidence for a subsurface ocean on Europa.

Ground-based spectroscopy of Jupiter's moon Europa, combined with gravity data, suggests that the satellite has an icy crust roughly 150 km thick and a rocky interior. In addition, images obtained by the Voyager spacecraft revealed that Europa's surface is crossed by numerous intersecting ridges and dark bands (called lineae) and is sparsely cratered, indicating that the terrain is probably significantly younger than that of Ganymede and Callisto. It has been suggested that Europa's thin outer ice shell might be separated from the moon's silicate interior by a liquid water layer, delayed or prevented from freezing by tidal heating; in this model, the lineae could be explained by repetitive tidal deformation of the outer ice shell. However, observational confirmation of a subsurface ocean was largely frustrated by the low resolution (>2 km per pixel) of the Voyager images. Here we present high-resolution (54 m per pixel) Galileo spacecraft images of Europa, in which we find evidence for mobile 'icebergs'. The detailed morphology of the terrain strongly supports the presence of liquid water at shallow depths below the surface, either today or at some time in the past. Moreover, lower-resolution observations of much larger regions suggest that the phenomena reported here are widespread.

Organics and other molecules in the surfaces of Callisto and Ganymede.

Five absorption features are reported at wavelengths of 3.4, 3.88, 4. 05, 4.25, and 4.57 micrometers in the surface materials of the Galilean satellites Callisto and Ganymede from analysis of reflectance spectra returned by the Galileo mission near-infrared mapping spectrometer. Candidate materials include CO2, organic materials (such as tholins containing C(triple bond)N and C-H), SO2, and compounds containing an SH-functional group; CO2, SO2, and perhaps cyanogen [(CN)2] may be present within the surface material itself as collections of a few molecules each. The spectra indicate that the primary surface constituents are water ice and hydrated minerals.

Galileo's First Images of Jupiter and the Galilean Satellites

The first images of Jupiter, Io, Europa, and Ganymede from the Galileo spacecraft reveal new information about Jupiter's Great Red Spot (GRS) and the surfaces of the Galilean satellites. Features similar to clusters of thunderstorms were found in the GRS. Nearby wave structures suggest that the GRS may be a shallow atmospheric feature. Changes in surface color and plume distribution indicate differences in resurfacing processes near hot spots on Io. Patchy emissions were seen while Io was in eclipse by Jupiter. The outer margins of prominent linear markings (triple bands) on Europa are diffuse, suggesting that material has been vented from fractures. Numerous small circular craters indicate localized areas of relatively old surface. Pervasive brittle deformation of an ice layer appears to have formed grooves on Ganymede. Dark terrain unexpectedly shows distinctive albedo variations to the limit of resolution.

Galileo multispectral imaging of the north polar and eastern limb regions of the moon.

Multispectral images obtained during the Galileo probe's second encounter with the moon reveal the compositional nature of the north polar regions and the northeastern limb. Mare deposits in these regions are found to be primarily low to medium titanium lavas and, as on the western limb, show only slight spectral heterogeneity. The northern light plains are found to have the spectral characteristics of highlands materials, show little evidence for the presence of cryptomaria, and were most likely emplaced by impact processes regardless of their age.