Full Ablation Research Articles

Doppler ultrasonography in acute pancreatitis

The crystallinity of GaN epitaxial layers on sapphire substrates following laser dicing was evaluated by Raman spectroscopy. Dicing was carried out using either full laser ablation or laser scribing followed by breaking. The results indicated that in a region within about 40 μm from the edges of the diced chips, the Raman peaks were shifted to lower wavenumber than near the chip center. The shifted peaks were at positions intermediate between those for the GaN epitaxial layer before dicing and those for a bulk GaN crystal. These results indicate that stress relaxation occurred near the edges of the diced chips.

Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice.

Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences of partial and full Sgta ablation in vivo using Cre-lox Sgta-null mice. Sgta+/− breeders generated viable Sgta−/− offspring, but at less than Mendelian expectancy. Sgta−/− breeders were subfertile with small litters and higher neonatal death (P < 0.02). Body size was significantly and proportionately smaller in male and female Sgta−/− (vs WT, Sgta+/− P < 0.001) from d19. Serum IGF-1 levels were genotype- and sex-dependent. Food intake, muscle and bone mass and adiposity were unchanged in Sgta−/−. Vital and sex organs had normal relative weight, morphology and histology, although certain androgen-sensitive measures such as penis and preputial size, and testis descent, were greater in Sgta−/−. Expression of AR and its targets remained largely unchanged, although AR localisation was genotype- and tissue-dependent. Generally expression of other TPR-containing proteins was unchanged. In conclusion, this thorough investigation of SGTA-null mutation reports a mild phenotype of reduced body size. The model’s full potential likely will be realised by genetic crosses with other models to interrogate the role of SGTA in the many diseases in which it has been implicated.

Lithium granule ablation and penetration during ELM pacing experiments at DIII-D

At DIII-D, lithium granules were radially injected into the plasma at the outer midplane to trigger and pace edge localized modes (ELMs). Granules ranging in size from 300 to 1000 microns were horizontally launched into H-mode discharges with velocities near 100m/s, and granule to granule injection frequencies less than 500Hz. While the smaller granules were only successful in triggering ELMs approximately 20% of the time, the larger granules regularly demonstrated ELM triggering efficiencies of greater than 80%. A fast visible camera looking along the axis of injection observed the ablation of the lithium granules. The duration of ablation was used as a benchmark for a neutral gas shielding calculation, and approximated the ablation rate and mass deposition location for the various size granules, using measured edge plasma profiles as inputs. This calculation suggests that the low triggering efficiency of the smaller granules is due to the inability of these granules to traverse the steep edge pressure gradient region and reach the top of the pedestal prior to full ablation.

Microwave ablation in treating intrahepatic recurrence of hepatocellular carcinoma after liver transplantation: An analysis of 11 cases

Purpose: This study was designed to evaluate the efficacy and safety of microwave ablation (MWA) in the treatment of intrahepatic recurrence of hepatocellular carcinoma (HCC) after liver transplantation. Materials and methods: Between October 2008 and August 2014, a total of 11 cases with 19 lesions were enrolled. All the subjects had confirmed HCC recurrence after liver transplantation by at least two types of enhanced imaging. Real-time monitoring and small ethanol doses were used as an additional technique to assist with ablation. Contrast imaging was performed to evaluate the technique efficacy. The technique efficacy rate, local tumour progression rate, 3, 6, 9, 12, 18 and 24 months survival rates, and the incidence of complications were comprehensively analysed. Results: The follow-up period ranged from 5–33 months. All tumours achieved full ablation. The first MWA technique efficacy rate was 84.2% (16/19), while the second technique efficacy rate was 100%. Local tumour progression was identified in three cases (15.8%) at 1, 3 and 7 months after MWA. The 3, 6, 9, 12, 18 and 24 months accumulative survival rates were 90.9%, 81.8%, 71.6%, 51.5%, 30.7% and 15.3%, respectively, the average survival time was 17.3 months (3.5–33 months). Mild side effects included five patients (45.4%) with fevers, three with (27.3%) nausea and vomiting, five (45.4%) with local pain, and eight (72.7%) with increased blood transaminase levels; no serious complications occurred. Conclusion: MWA treatment is a promising technique for intrahepatic recurrence after liver transplantation without serious complications or side effects.

Evaluation of crystallinity of GaN epitaxial layer after wafer dicing

The crystallinity of GaN epitaxial layers on sapphire substrates following laser dicing was evaluated by Raman spectroscopy. Dicing was carried out using either full laser ablation or laser scribing followed by breaking. The results indicated that in a region within about 40μm from the edges of the diced chips, the Raman peaks were shifted to lower wavenumber than near the chip center. The shifted peaks were at positions intermediate between those for the GaN epitaxial layer before dicing and those for a bulk GaN crystal. These results indicate that stress relaxation occurred near the edges of the diced chips.

High-resolution LA-ICP-MS trace element mapping of igneous minerals: In search of magma histories

We report experiments on optimisation of LA-ICP-MS mapping as a tool for visualising and quantifying internal structure of trace element concentration in igneous minerals. The experimental design was refined with maps on clinopyroxene and amphibole macrocrysts (mainly antecrysts) from a porphyritic lamprophyre in NE Spain, as well as on a high precision metal wire grid. In terms of spatial resolution, we demonstrate with scanning electron microscope and white light interferometry that a full ablation removes between 0.4 and 0.7μm of material, depending on ablation parameters. Maps were produced with square laser beam spots of 12 and 24μm. It was found that complexities can be resolved in the sample even though they are smaller than the beam diameter (e.g., 7–10μm discontinuities using 12μm laser beam). Resolution in x and y was found to be identical, probably reflecting the fast washout of the two-volume ablation cell and the short total dwell time of the analyte menu selected. Due to the excellent stage reproducibility and the limited ablation depth, it is feasible to re-ablate the identical map area many times employing different instrument parameters or analyte menus.On the magmatic crystals, LA-ICP-MS maps define very sharp compositional zoning in trace elements, highlighting complex crystallisation histories where ‘normal’ magmatic fractionation is not the only process. Events of mafic recharge are easily recognised as zones enriched in compatible metals such as Cr, Ni or Sc. Further, trace element maps reveal complexities in mineral zoning previously undetectable with petrography or major element data. These include resorbed primitive cores and oscillatory zoning within apparently homogeneous mineral zones. Therefore, LA-ICP-MS mapping opens a new window of opportunity for analysis of magmatic histories. The wide combination of instrumental parameters, such as laser beam size, scan speed and repetition rate, make it possible to carry out experiments at different levels of detail. We recommend a two-step approach to mapping. The initial step involves rapid maps to gain an overview of potential complexities in the sample; this enhances representativeness of the analysed materials, as a large number of crystals and trace elements can be tested in little time. Subsequently, detailed maps can be carried out on areas of interest. An additional functionality is to create 1D-profiles from 2D-maps. The potential of the technique to unveil compositional complexities efficiently and at greater detail than traditional microanalysis will help to improve our understanding of processes in the magmatic environment and beyond.

Intestinal Depletion of NaPi-IIb/Slc34a2 in Mice: Renal and Hormonal Adaptation.

The Na(+) -dependent phosphate-cotransporter NaPi-IIb (SLC34A2) is widely expressed, with intestine, lung, and testis among the organs with highest levels of mRNA abundance. In mice, the intestinal expression of NaPi-IIb is restricted to the ileum, where the cotransporter localizes specifically at the brush border membrane (BBM) and mediates the active transport of inorganic phosphate (Pi). Constitutive full ablation of NaPi-IIb is embryonically lethal whereas the global but inducible removal of the transporter in young mice leads to intestinal loss of Pi and lung calcifications. Here we report the generation of a constitutive but intestinal-specific NaPi-IIb/Slc34a2-deficient mouse model. Constitutive intestinal ablation of NaPi-IIb results in viable pups with normal growth. Homozygous mice are characterized by fecal wasting of Pi and complete absence of Na/Pi cotransport activity in BBM vesicles (BBMVs) isolated from ileum. In contrast, the urinary excretion of Pi is reduced in these animals. The plasma levels of Pi are similar in wild-type and NaPi-IIb-deficient mice. In females, the reduced phosphaturia associates with higher expression of NaPi-IIa and higher Na/Pi cotransport activity in renal BBMVs, as well as with reduced plasma levels of intact FGF-23. A similar trend is found in males. Thus, NaPi-IIb is the only luminal Na(+) -dependent Pi transporter in the murine ileum and its absence is fully compensated for in adult females by a mechanism involving the bone-kidney axis. The contribution of this mechanism to the adaptive response is less apparent in adult males.

FLT Imaging Reveals Kinetics and Biology of Engraftment after Myeloablative HSCT

▪Bone marrow failure is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT) due to complications associated with prolonged neutropenia. Using the positron emission tomography (PET) imaging probe, 3’-deoxy-3 18F-fluorothymidine (18FLT), we illustrate HSC homing very early after myeloablative HSCT in adults in vivo. In our prospective trial, NCT01338987, we imaged 14 patients undergoing myeloablative transplantation with Cytoxan and total body irradiation and evaluated corresponding uptake of radiotracer 18FLT in osseous structures throughout the bone marrow compartment following full myeloblation, early engraftment, and hematopoietic reconstitution. 18FLT was safe and did not delay engraftment. Objective increases in 18FLT uptake measured by standardized uptake value (SUV) revealed evidence of stem cell homing to medullary bone marrow sites within 5 days of donor cell infusion. In patients without relapse (n=11), mean thoracic spine SUV was greater among patients with rapid (<21 days) as compared to slow engraftment (≥21 days). Using SUV, we could differentiate full ablation (SUV of 0.65) from early engraftment at day +5-6 (SUV 1.1, p <0.05). 18FLTsignal increases revealed a consistent pattern of marrow recovery that recapitulated fetal ontogeny, claiming sites of hematopoiesis that are normally dormant in adults. These findings were substantiated with in vitro cellular recovery data. 18FLT SUV could also predict marrow recovery after secondary graft failure without additional HSC infusion. In summary, our data show that 18FLT reveals homing, kinetics, and biology of hematopoietic engraftment in adults in vivo.18FLT could predict engraftment very early after HSCT and could be of value to predict primary or secondary graft failure in high risk populations, such as recipients of cord blood transplantation or haplo-identical transplantation. DisclosuresNo relevant conflicts of interest to declare.

Monitoring of tumor radio frequency ablation using derivative spectroscopy.

Despite the widespread use of radio frequency (RF) ablation, an effective way to assess thermal tissue damage during and after the procedure is still lacking. We present a method for monitoring RF ablation efficacy based on thermally induced methemoglobin as a marker for full tissue ablation. Diffuse reflectance (DR) spectra were measured from human blood samples during gradual heating of the samples from 37 to 60, 70, and 85°C. Additionally, reflectance spectra were recorded real-time during RF ablation of human liver tissue ex vivo and in vivo. Specific spectral characteristics of methemoglobin were extracted from the spectral slopes using a custom optical ablation ratio. Thermal coagulation of blood caused significant changes in the spectral slopes, which is thought to be caused by the formation of methemoglobin. The time course of these changes was clearly dependent on the heating temperature. RF ablation of liver tissue essentially led to similar spectral alterations. In vivo DR measurements confirmed that the method could be used to assess the degree of thermal damage during RF ablation and long after the tissue cooled.

Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits.

Within the hippocampal circuitry, the basic function of the dentate gyrus is to transform the memory input coming from the enthorinal cortex into sparse and categorized outputs to CA3, in this way separating related memory information. New neurons generated in the dentate gyrus during adulthood appear to facilitate this process, allowing a better separation between closely spaced memories (pattern separation). The evidence underlying this model has been gathered essentially by ablating the newly adult-generated neurons. This approach, however, does not allow monitoring of the integration of new neurons into memory circuits and is likely to set in motion compensatory circuits, possibly leading to an underestimation of the role of new neurons. Here we review the background of the basic function of the hippocampus and of the known properties of new adult-generated neurons. In this context, we analyze the cognitive performance in mouse models generated by us and others, with modified expression of the genes Btg2 (PC3/Tis21), Btg1, Pten, BMP4, etc., where new neurons underwent a change in their differentiation rate or a partial decrease of their proliferation or survival rate rather than ablation. The effects of these modifications are equal or greater than full ablation, suggesting that the architecture of circuits, as it unfolds from the interaction between existing and new neurons, can have a greater functional impact than the sheer number of new neurons. We propose a model which attempts to measure and correlate the set of cellular changes in the process of neurogenesis with the memory function.

Effects of different parameters in the fast scanning method for HIFU treatment

High-intensity focused ultrasound is a promising method for the noninvasive treatment of benign and malignant tumors. This study analyzes the effects of scanning path, applied power, and geometric characteristics of the transducer on ablation using fast scanning method, a new scanning method that uses high-intensity focused ultrasound at different blood perfusion levels. Two transducers, six scanning paths, and three focal patterns were used to examine the ablation results of the fast scanning method using power densities from 1.35 × 10(7) W∕m(3) to 4.5 × 10(7) W∕m(3) and blood perfusion rates from 2 × 10(-3) ml∕ml∕s to 16 × 10(-3) ml∕ml∕s. The Pennes equation was solved using the finite-difference time-domain method to simulate the heating procedure. Based on the results of the fast-scanning method, the different scanning paths exhibited small effect on the total treatment time supported by both simulation and least-square fit. Similar-sized lesions can result from the five different repeated paths, whereas a random path may lead to relative large fluctuations in ablation volume because of asymmetry of the lesions. Higher power levels increase the lesion volume and decrease the treatment time required for ablating a target area using the fast scanning method, whereas increased blood perfusion has the opposite effect on ablation volume and treatment time. A symmetric lesion can be produced through fast scanning method using a 65-element and a 90-element transducer. However, lesion production using the same operation scheme differs between the two transducers. Unlike traditional scanning methods, fast scanning method produces a planned lesion regardless of scanning path, as long as the path consists of repeated subsequences. This attribute makes fast scanning method an easy-operation scheme that produces relatively large symmetric lesions in homogeneous tissues. Applied power is the most important factor; however, high blood perfusion levels can limit or even hinder the full ablation of the target area. Therefore, tissue perfusion and transducer type should be given special attention to ensure the success and safety of ablation treatment.

Maternal administration of busulfan before in utero transplantation of human hematopoietic stem cells enhances engraftments in sheep

In utero transplantation (IUT) of human hematopoietic stem cells has been conducted in sheep, which are used as large animal models of human hematopoietic reconstitution and models for clinical IUT; however, the levels of engraftment have generally been low. Busulfan (BU), a myeloablative agent, is often administered to patients before hematopoietic stem cells transplantation to improve the engraftment. In this study, hematopoietic activity was evaluated in adult sheep after administering BU at different doses. Next, pregnant ewes were administered BU, and dams as well as their fetuses were evaluated, as BU readily crosses the sheep placenta. Then, the BU dose with the desired outcomes was selected and administered to pregnant ewes at 2 or 6 days before performing IUT using human cord blood CD34(+) cells. The engraftment was evaluated in recipients that underwent IUT in the presence or absence of BU. As a result, hematopoietic activity was safely and transiently suppressed in adult sheep treated with 5 to 7.5 mg/kg BU. BU crossed the sheep placenta, and fetal sheep were indeed conditioned by administering 3 mg/kg BU to pregnant ewes. Engraftment of human CD34(+) cells in fetal recipients was enhanced when IUT was carried out 6 days post-BU. Up to 3.3% engraftment levels (in terms of bone marrow colony-forming units) were achieved with the IUT of 0.72 to 2.4 million CD34(+) cells when BU was used. BU can be administered to pregnant ewes to effectively condition the fetal recipient for IUT with enhanced engraftment of donor cells.

Cool-1/βPIX functions as a guanine nucleotide exchange factor in the cycling of Cdc42 to regulate insulin secretion.

Second-phase insulin release requires the sustained mobilization of insulin granules from internal storage pools to the cell surface for fusion with the plasma membrane. However, the detailed mechanisms underlying this process remain largely unknown. GTP-loading of the small GTPase Cdc42 is the first glucose-specific activation step in the process, although how glucose triggers Cdc42 activation is entirely unknown. In a directed candidate screen for guanine nucleotide exchange factors (GEFs), which directly activate small GTPases, Cool-1/βPix was identified in pancreatic islet beta cells. In support of its role as the beta cell Cdc42 GEF, βPix coimmunoprecipitated with Cdc42 in human islets and MIN6 beta cells in a glucose-dependent manner, peaking just prior to Cdc42 activation. Furthermore, RNAi-mediated βPix reduction by 50% corresponded to full ablation of glucose-induced Cdc42 activation and significant attenuation of basal and glucose-stimulated insulin secretion. Of the two Cdc42 guanine nucleotide dissociation inhibitor (GDI) proteins identified in beta cells, βPix competed selectively with caveolin-1 (Cav-1) but not RhoGDI in coimmunoprecipitation and GST-Cdc42-GDP interaction assays. However, a phospho-deficient Cav-1-Y14F mutant failed to compete with βPix; Cav-1(Tyr14) is an established phosphorylation site for Src kinase. Taken together, these data support a new model, wherein glucose stimulates Cav-1 and induces its dissociation from Cdc42, possibly via Src kinase activation to phosphorylate Cav-1(Tyr14), to promote Cdc42-βPix binding and Cdc42 activation, and to trigger downstream signaling and ultimately sustain insulin release.

Increased CDK5 Expression in HIV Encephalitis Contributes to Neurodegeneration via Tau Phosphorylation and Is Reversed with Roscovitine

Recent treatments with highly active antiretroviral therapy (HAART) regimens have been shown to improve general clinical status in patients with human immunodeficiency virus (HIV) infection; however, the prevalence of cognitive alterations and neurodegeneration has remained the same or has increased. These deficits are more pronounced in the subset of HIV patients with the inflammatory condition known as HIV encephalitis (HIVE). Activation of signaling pathways such as GSK3β and CDK5 has been implicated in the mechanisms of HIV neurotoxicity; however, the downstream mediators of these effects are unclear. The present study investigated the involvement of CDK5 and tau phosphorylation in the mechanisms of neurodegeneration in HIVE. In the frontal cortex of patients with HIVE, increased levels of CDK5 and p35 expression were associated with abnormal tau phosphorylation. Similarly, transgenic mice engineered to express the HIV protein gp120 exhibited increased brain levels of CDK5 and p35, alterations in tau phosphorylation, and dendritic degeneration. In contrast, genetic knockdown of CDK5 or treatment with the CDK5 inhibitor roscovitine improved behavioral performance in the water maze test and reduced neurodegeneration, abnormal tau phosphorylation, and astrogliosis in gp120 transgenic mice. These findings indicate that abnormal CDK5 activation contributes to the neurodegenerative process in HIVE via abnormal tau phosphorylation; thus, reducing CDK5 might ameliorate the cognitive impairments associated with HIVE.

Layer selective laser ablation for local contacts to thin emitters

High efficiency solar cells require high generation and low recombination rates. High bulk lifetime, well passivated surfaces, and lowly doped thin emitters allow for low recombination rates. Thin passivated emitters should be contacted locally in order to avoid excessive contact recombination. This is common practice for front junction solar cells but is also advantageous for back junction cells. We analyze a novel layer selective laser ablation process. From a passivating stack composed of 70 nm silicon nitride that we deposit on top of 35 nm of amorphous silicon we selectively ablate the silicon nitride layer. Transmission electron microscopy investigations confirm the full ablation of the silicon nitride layer. After the ablation process, a 17 nm-thick amorphous silicon layer remains on the substrate. The crystalline silicon substrate shows no dislocations after the process. Evaporating aluminum on top of the locally ablated nitride layers forms local contacts of the aluminum to the silicon. © 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of SiliconPV 2011.

Modeling surface-roughness/solar-ablation feedback: application to small-scale surface channels and crevasses of the Greenland ice sheet

AbstractSurface roughness enhances the net ablation rate associated with direct solar radiation relative to smooth surfaces, because roughness allows solar energy reflected from one part of the surface to be absorbed by another part. In this study we examine the feedback between solar-radiation-driven ablation and growth of surface roughness on the Greenland ice sheet, using a numerical model of radiative transfer. Our experiments extend previous work by examining: (1) the effects of diurnal and seasonal variation of solar zenith angle and azimuth relative to incipient roughness features, (2) the evolution of roughness geometry in response to radiatively driven ablation and (3) the relative solar energy collection efficiencies of various roughness geometries and geographic locations and orientations. A notable result of this examination is that the time evolution of the aspect ratio of surface features under solar-driven ablation collapses onto a roughly universal curve that depends only on latitude, not the detailed shape of the feature. The total enhancement of surface melt relative to a smooth surface over a full ablation season varies with this ratio, and this dependence suggests a way to parameterize roughness effects in large-scale models that cannot treat individual roughness features. Overall, our model results suggest that surface roughness at the latitudes spanned by the Greenland ice sheet tends to dissipate as the ablation season progresses.

Effect of Wire Diameter and Addition of an Axial Magnetic Field on the Dynamics of Radial Wire Array $Z$-Pinches

The operation of radial wire array Z-pinches driven by a 1-MA 250-ns current pulse was studied. Variation in the cathode diameter and wire diameter does not affect the overall plasma dynamics but controls the time of wire breakage and the time of pinch formation. The measured times of full wire ablation at the cathode were used to determine the ablation velocity (V abl), and the results give a scaling V abl ~ (wire diameter)-0.46. Experiments with added axial magnetic field show an increase in the pinched plasma diameter, possibly due to the compression of the axial magnetic flux by the imploding plasma.

Nonsense-Mediated mRNA Decay Is Essential for the Hematopietic Compartement.

Nonsense-mediated mRNA decay (NMD) is a conserved cellular surveillance system that degrades mRNAs with premature termination codons (PTCs). PTC-containing transcripts can arise from faulty events such as erroneous mRNA processing events as well as mutations, and their translation may lead to the synthesis of deleterious proteins. In addition to serving as a genomic protection system, experiments in tissue culture cells have demonstrated that NMD regulates 5% of the normal mRNA pool suggesting that the NMD pathway may have a broader role in gene regulation. Finally, NMD has also been proposed to be important during lymphocyte development as a tool of riding the cells of transcripts resulting from unproductive re-arrangements events of T cell receptor and immunoglobulin genes. Although NMD has been studied extensively at the biochemical level, the actual role and importance of NMD in the mammalian organism has not been investigated. We therefore generated a conditional Upf2 knock-out mouse line (UPF2 being an essential NMD factor) which we crossed to different hematopoietic relevant Cre expressing lines. Full ablation of UPF2 (using the inducible Mx1-Cre deleter) led to complete loss of all nucleated cells in the bone marrow and death of the animals within 10 days. A similar phenotype was observed when Upf2fl/fl; Mx1Cre BM cells were transplanted into lethally irradiated WT recipients and induced with poly-IC, demonstrating the cell autonomous nature of the phenotype. Deletion of UPF2 in the myeloid lineage using the LysM-Cre deleter resulted in efficient ablation of UPF2 and the absence of NMD in reporter transfected bone marrow derived macrophages (BMDMs). However, the steady state levels of myeloid cells appeared unaltered. Finally, deletion of UPF2 in T cells using a Lck-Cre deleter led to a marked reduction of both CD4/CD8 double-positive and single-positive T cells and accumulation of PTC containing transcripts. Gene expression profiling experiments of BMDM and thymocytes from WT and UPF2-ablated animals identified a common core set of 27 up-regulated genes consistent with the role of NMD as a mRNA degrading system. The gene expression profiling data suggest that ablation of NMD leads to accumulation of unfolded proteins. In summary, these studies demonstrate the vital and cell-autonomous role of NMD in the hematopoietic system.

Phase I/II Trial of High Intensity Focused Ultrasound for the Treatment of Previously Untreated Localized Prostate Cancer

We examined the safety and potential efficacy of transrectally delivered high intensity focused ultrasound for the full gland ablation of previously untreated localized prostate cancer. A total of 20 patients with localized prostate cancer underwent 1 to 3 high intensity focused ultrasound treatments of the prostate. The primary outcome was safety and the secondary outcomes were prostate specific antigen, prostate biopsy and quality of life measures. A total of 19 patients had complete followup. Serious adverse events related to treatment were limited with the most common adverse event being transient urinary retention more than 30 days in duration in only 10% of patients. Rectal injury occurred in 1 patient. With 1 to 3 treatments 42% of the patients achieved prostate specific antigen less than 0.5 ng/ml and a negative prostate biopsy. High intensity focused ultrasound in patients with previously untreated prostate cancer is generally well tolerated and it has the potential to completely ablate the prostate gland. With further refinement of the optimal treatment dose and technique this technology has the potential to be an effective form of therapy for localized prostate cancer.

Efficacy of Laser-Activated Gold Nanoshells in Ablating Prostate Cancer Cells in Vitro

Nanoshells (NS) are nanoparticles consisting of a dielectric silica core covered by a thin gold shell. Nanoshells can be designed to absorb near-infrared (NIR) light strongly to generate heat and provide optically guided hyperthermic ablation. Laser-activated gold nanoshells (LAGN) may offer a minimally invasive targeted ablative treatment for prostate cancer. We studied the in-vitro effectiveness of LAGN ablation on human prostate cancer cells. Two human prostate cancer (PCa) cell lines, PC-3 and C4-2, were grown to 80% confluency in T medium with 5% fetal bovine serum. In order to determine a threshold concentration of gold nanoshells (GNS) needed to achieve full cellular ablation, dose titration was performed. In subsequent experiments, GNS were added to PCa cells in phosphate-buffered saline at concentrations above the predetermined threshold. The cells were then exposed to NIR light (810 nm, 88 W/cm2) for 5 minutes and stained immediately for viability using the Calcein AM assay. For determining long-term cell survival, the crystal violet assay was employed. The GNS could be evenly distributed across the culture plates. A ratio of 5000 GNS per PCa cell was critical for achieving cell kill. Cells treated with GNS + NIR demonstrated a laser-specific zone of cell death. The crystal violet viability assay confirmed consistent cell death rather than induction of cell dormancy. Cells treated with GNS alone or with NIR light alone demonstrated no toxicity. Laser-activated gold nanoshells can ablate human PCa cells in vitro. This nanoparticle technology is an attractive therapeutic agent for selective tumor ablation.