Efficient Photocatalytic Reduction of Hexavalent Chromium by BiVO4-Decorated MXene Photocatalysts and Their Charge Carrier Dynamics.

The synergistically MXene (Ti3C2Tx) co-catalyst-decorated BiVO4-based heterostructured photocatalysts have been synthesized by a hydrothermal approach with varied loading concentrations of MXene (Ti3C2Tx) to drive the hexavalent chromium reduction efficiently. The formation of the heterostructured photocatalyst was confirmed by the appearance of X-ray diffraction (XRD) peaks corresponding to the monoclinic BiVO4 phase and MXene (Ti3C2Tx) and also the antisymmetric (834 cm-1) and symmetric stretching (715 cm-1) of tetrahedral VO4 and D (1330 cm-1) and G (1570 cm-1) bands corresponding to MXene (Ti3C2Tx) in the Raman spectrum. The worm-like structures of BiVO4 nanocrystals grew onto the lamellar sheets of MXene (Ti3C2Tx), as shown by field emission scanning electron microscopy (FESEM), and has an increased surface area of 15.62 m2g-1 in the case of BVO-20-TC. X-ray photoelectron spectroscopy (XPS) analysis confirms the presence of V5+ and Ti3+states, and the uniform distribution of BiVO4 nanocrystals over lamellar sheets of MXene (Ti3C2Tx) is evident from energy-dispersive X-ray (EDX) analysis. The ultraviolet-diffuse reflectance spectroscopy (UV-DRS) spectra suggest a decrease in the band gap energy of BVO-20-TC to 2.335 eV, promoting a higher degree of visible light harvesting. Upon optimization, by varying the pH, the amount of the photocatalyst, and the concentration of Cr(IV), BVO-20-TC exhibits the highest photocatalytic efficiency (96.39%) while using a Cr(VI) concentration of 10 ppm at pH 2 and 15 mg of the photocatalyst, and the photoreduction of Cr(VI) to Cr(III) follows the pseudo-first-order reaction. The decrease in the PL intensity in BVO-20-TC reveals a faster transfer of electrons from MXene (Ti3C2Tx) to BiVO4. Further, the higher degree of band bending at the BiVO4/MXene (Ti3C2Tx) heterojunction, revealed from the Mott-Schottky analysis, facilitates efficient charge transfer and eventually faster and efficient photoreduction of Cr(VI) to Cr(III). The reusability and stability test undertaken for BVO-20-TC reveals that even after five cycles, the Cr (VI) photoreduction efficacy is retained. This work provides insights into photoreduction of Cr (VI) by using such heterostructures.

Efficient Photocatalytic CO2 Reduction with High Selectivity for Ethanol by Synergistically Coupled MXene-Ceria and the Charge Carrier Dynamics.

The primary factors that govern the selectivity and efficacy of CO2 photoreduction are the degree of activation of CO2 on the active surface sites of photocatalysts and charge separation/transfer kinetics. In this context, the rational synthesis of heterostructured MXene-coupled CeO2-based photocatalysts with different loading concentrations of Ti3C2MXene via a one-step hydrothermal approach has been undertaken. These photocatalysts exhibit a shift in X-ray diffraction peaks to higher 2θ values and changes in stretching vibrations of 5 wt % Ti3C2MXene/CeO2(5-TC/Ce) that indicate interaction between Ti3C2MXene and CeO2. Moreover, XPS analysis confirms the presence of the Ce3+/Ce4+ states. A sharp band at 2335 cm-1 observed during the CO2 photoreduction process corresponds to bidentate b-CO32-, which facilitates the adsorption of CO2 at the surface of the catalyst as revealed by the TPD analysis. Furthermore, the Schryvers test and NMR analysis were undertaken to confirm the formaldehyde intermediate formation during CO2 photoreduction to C2H5OH. The decrease in emission intensity, reduced lifetimes (2.68 ns), and lower interfacial resistance, as revealed by PL, TR-PL, and EIS analysis, imply an efficient charge separation and charge transfer in the case of the Ti3C2MXene/CeO2 heterojunction. The decrease in the intensity of peaks in the EPR spectrum in the case of 5-TC/Ce further confirms efficient charge transfer kinetics across the interface. The optimized 5-TC/Ce shows CO2 reduction with a drastically enhanced yield of ethanol on the order of 6127 µmol g-1 at 5 h with 98% selectivity and 7.54% apparent quantum efficiency, which is 6-fold higher than that of ethanol produced by bare CeO2. Herein, CeO2 that acts as a redox couple (Ce3+/Ce4+) when coupled with MXene having a metallic nature that reduces the electron transfer resistance is in unison, enabling an enhanced mobilization of electrons. Thereby, the synergistic coupling of Ti3C2MXene with CeO2 leads to an efficient photoreduction of CO2 under visible light illumination.

Enhanced Nitrogen Reduction to Ammonia by Surface- and Defect-Engineered Co-catalyst-Modified Perovskite Catalysts under Ambient Conditions and Their Charge Carrier Dynamics.

An electrocatalytic nitrogen reduction reaction is considered a potential approach for green ammonia production─a zero-carbon fertilizer, fuel, and energy storage for renewable energy. To harness the synergistic properties of perovskites, the inherent dipole moment due to their non-centrosymmetric structure (that facilitates better charge separation), oxygen vacancies, and the presence of Ni metal sites that permit activation and reduction of N2 efficiently, the NiTiO3-based nanoelectrocatalysts have been synthesized. Further, these catalysts have been modified with ultra-small metal nanocrystal co-catalysts to form heterointerfaces that not only aid to improve the charge separation but also activate N2 and lower overpotential requirements. The appearance of peaks corresponding to (012), (104), (110), (11-3), (024), (11-6), (018), (027), and (300) confirms the formation of rhombohedral NiTiO3. The shift in the XRD peak corresponding to the (104) plane to a smaller 2θ value and peak shifting and widening of Raman spectra imply the lattice distortion that signifies the formation of Pd-NiTiO3 and Pt-NiTiO3 heterojunction electrocatalysts with the loadings of 0.4 and 0.3 wt % of Pd and Pt, respectively, as confirmed by ICP-OES analysis. The detailed XPS analysis reveals the presence of Pd (0), Pd (II), and Pt (0), Pt (II) in respective electrocatalysts. The appearance of XPS peaks at 528.7 and 531.1 eV suggests the presence of oxidative oxygen species (O2-/O-) and the presence of oxygen defects due to oxygen vacancy. The detailed nitrogen reduction (NRR) investigation exhibits a 5-fold enhancement in ammonia yield rate (∼14.28 µg h-1 mg-1 at -0.003 V vs RHE), a faradic efficiency of 27% (at 0.097 V vs RHE) for Pd-NiTiO3 electrocatalysts than that for bare NiTiO3 (3.08 µg h-1 mg-1), and 9-folds higher than that of the activity shown by the commercial TiO2 (P25) (1.52 µg h-1mg-1). The formation of ammonia was further confirmed by using isotopic nitrogen as the feeding gas. Furthermore, the highest NRR is observed at lower cathodic potential (-0.003 V vs RHE) in the case of the Pd-NiTiO3 electrocatalyst than that of the Pt-NiTiO3 electrocatalyst (-0.203 V vs RHE), implying significantly reduced overpotential requirement. Such enhanced NRR activity with lower overpotential requirement in the case of the Pd-NiTiO3 electrocatalyst is due to efficient charge separation as shown by the semicircle Nyquist plot, decreased photoluminescence emission intensity, shorter average lifetime (∼29 ns) of excitons, appropriate band bending, and improved activation of N2 by the oxygen vacancies and heterointerface formed between Pd nanocrystals and NiTiO3. Furthermore, no change is observed in the current density, after stabilization in the initial few seconds, even up to 2 h, which signifies that these electrocatalysts are stable. The structural and morphological integrity of the optimized catalyst remained even after the nitrogen reduction reactions, as revealed by no significant change observed in FESEM, elemental mapping, and EDS analysis.

Abdominal Manifestations of Multisystem Inflammatory Syndrome in Children: A Single-Center Experience.

OBJECTIVES: We reviewed the cases of probable multisystem inflammatory syndrome in children (MIS-C) to identify those cases that mimicked surgical emergencies. METHODS: Records of children managed for MIS-C during a 15-month period between March, 2020 and April, 2021 were retrieved. Data on clinical presentation, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR report, SARS-CoV-2 antibody status, blood investigations, radiological investigations and management were collected. RESULTS: A total of 28 out of 83 children with probable MIS-C had acute abdominal symptoms and signs. Fifteen children had mild features like diffuse abdominal pain or non-bilious vomiting, and the remaining 13 (46.2%) had severe abdominal signs or bilious vomiting. Four children worsened with conservative treatment for MIS-C and were detected with perforated appendicitis. Two more children developed recurrent appendicitis on follow up. One child with appendicitis who underwent laparoscopic appendectomy, later manifested with MIS-C. CONCLUSION: Surgical abdominal emergencies may be confused with or occur concurrently in children with MIS-C that should be identified with a high index of suspicion.

Drug infused Al2O3-bioactive glass coatings toward the cure of orthopedic infection.

A unique implant coated substrate with dual-drug-eluting system exhibiting antibacterial, anti-inflammatory, and bone regenerative capacity has been fabricated using spray pyrolysis deposition (SPD) method. Bioglass (BG) and BG-alumina (BG-Al) composites coatings with different concentrations of Al incorporated on BG network over the Cp-Ti substrate were fabricated using SPD technique. Phase purity of BG and BG-Al composites were analyzed by XRD in which Na2Ca2Si3O9 and ß-Na2Ca4(PO4)2SiO4) and Na7.15(Al7.2Si8.8O32) phases were formed. Surface morphology of the coated substrates was analyzed by SEM. Uniformity of the coatings were evaluated by surface profilometer and the uniform distribution the nanoparticles were confirmed with Elemental mapping. Systematically, each apatite layer formation on coated substrate was confirmed by immersing the samples for 1, 3, and 7 days in simulated body fluid and the needle-like structure was characterized using SEM. Cumulative release of Tetracycline hydrochloride (Tet) antibiotic and Dexamethasone (Dex) anti-inflammatory drug-loaded BG-Al and BG-Al composite-coated substrate were studied for 24 h. Antibacterial activity of the coated substrates were evaluated by time-dependent growth inhibition and minimal inhibitory concentration (MIC) assays in which BG-Al and BG-Al composite loaded with Tet showed considerable growth inhibition against S. aureus. Osteoblast-like cells (MG-63) exhibited profound proliferation with no cytotoxic effects which was due to release of Dex drug-coated substrates. Thus, surface modification of Cp-Ti substrate with BG, BG-Al composites coatings loaded with Tet and Dex drug can be considered for post-operative orthopedic implant infection application.

Interplay between surface chemistry and osteogenic behaviour of sulphate substituted nano-hydroxyapatite.

Surface potential and chemical compositions of the bioceramics are the core of therapeutic effect and are key factors to trigger the interfacial interactions with surrounding hard and soft tissues to repair and regeneration. Ionic substitution in hydroxyapatite (Hap) lattice significantly influences the zeta potential from -16.46 ± 0.66 mV to -6.01 ± 0.68 mV as well as an average nano-rod length from ~40 nm to ~26 nm with respect to SO42- ion content. Moreover, the surface chemistry of Hap is mainly inter-related to SO42- substitution rate at PO42- site. Specifically, nano-sized feature with lowered negative surface potential influences the protein adsorption via their weak repulsive or attractive forces. Bovine serum albumin (BSA) and lysozyme (LSZ) adsorption studies confirmed the increased affinity to active binding sites of Hap's surface. Further, SO42- ion substituted Hap (SNHA) showed improved in vitro biomineralization activity and alkaline phosphatase activity. Expression of osteogenic biomarkers such as collagen I, V, osteopontin and osteocalcin were evaluated in Saos-2 and MC3T3-E1 cells. Gene expression of these markers was influenced by SO42- ion content in Hap (maximum with 10SNHA). Altogether, these data emphasizes that chemical composition and surface properties are dominant aspect in bioceramic development towards bone regeneration.

Bioactive, degradable and multi-functional three-dimensional membranous scaffolds of bioglass and alginate composites for tissue regenerative applications.

With a worldwide increase in the aged populace and associated geriatric diseases, there is an enormous need for the regeneration of degenerated organ systems. For this purpose, bioactive glass particulate (nBG) integrated alginate (Alg) composite membrane scaffolds were fabricated by a sol-gel assisted freeze-drying method and validated for their multifunctional utility in regenerative medicine. The presence of the combeite highly crystalline structure of nBG and Alg amorphous broad peaks were confirmed. Repetitive peaks from acids along with stretching confirmed the chemical interactions of the composites. Swelling ability, porosity, and in vitro degradation and biomineralization were analysed for up to 7 days. The results indicated that reduced swelling and degradation enhanced apatite formation. Hemocompatibility and the hemostatic properties on scaffolds were also systematically investigated. Additionally, significant cyto-compatibility and proliferation were noted in a culture with KB3-1. Further 3-D co-cultures with HDF cells and KB3-1 cells exhibited spheroid formation on Alg, nBG/Alg and nBG-Zr/Alg with profound dynamism required to establish organoids of interest. Thus, the results indicate that these 3D hydrogel membranes could offer infinite possibilities in the field of regenerative medicine, notably as an extracellular matrix (ECM) supporting the regeneration of bone, intra-vascularization, and neo-tissue formation, such as cartilage and ligaments.

Effect of Titania Concentration in Bioglass/TiO2 Nanostructures and Its In Vitro Biological Property Assessment.

Bioglass 45S5 (45% SiO2-24.5% NaO-24.5% CaO-6% P2O5) is a unique bioactive material, which is being used for bone and dental substitution. This system has been highly preferred for its osteoconductive and osteoinductive performance. Despite its attractive bioactivity, there are limitations in using this material for orthopedic and dental applications due to its poor processability and mechanical strength. To improve the load-sharing and stress distribution, TiO2 nanoparticles have been introduced into the nanoBioglass (nBG) by sol-gel method. The structural analyses of the samples were confirmed using X-ray diffraction, Raman-spectroscopy and FTIR. The morphologies of the samples were characterized by FESEM. The apatite formation of the nBG/TiO2 composites was investigated by immersing the samples in simulated body Fluid (SBF) solution for 1 and 3 days, which reveals the acceptable compatibility for different concentrations of all the composition. Hemolysis studies of the nanobiomaterials were carried out to understand the interactions of biomaterials with blood which shows 0.2%-2% of lysis which is acceptable as per ASTM standard. Cell culture and cell proliferation studies of bioglass, nBG/TiO2 nanocomposite on MG-63 pre-osteoblast cell line for 24 h, 48 h and 72 h showed 80% to 95% of cell viability. Also, it was found that the nBG/TiO2 bio-nanocomposites containing low content of titania had good bioactivity properties that is comparable to cortical bone. Hence, nBG/TiO2 bio-nanocomposites are greatly promising for medical applications such as bone substitutes especially in load-bearing sites.

Salivary and serum level of CYFRA 21-1 in oral precancer and oral squamous cell carcinoma.

BACKGROUND: CYFRA 21-1, a constituent of the intermediate filament proteins of epithelial cells, is known to be increased in many cancers. This study was designed to estimate the levels of salivary and serum CYFRA 21-1 in patients with oral precancer and oral squamous cell carcinoma (OSCC) and compare them with healthy controls. MATERIALS AND METHODS: Each group comprised of 100 subjects. Saliva and blood samples were collected from patients with OSCC, premalignant subjects, and normal healthy subjects. Serum and salivary CYFRA 21-1 levels were measured by enzyme-linked immunosorbent assay. Appropriate statistical tests were employed to assess diagnostic potency of CYFRA 21-1. RESULTS: We found a significant increase in CYFRA 21-1 level in OSCC compared with PML and healthy subjects. Salivary CYFRA 21-1 levels in OSCC was threefold higher when compared to serum levels. PML group showed increased salivary CYFRA 21-1 when compared to control subjects, but it was significantly lower compared with OSCC. Receiver operator characteristic curve analysis showed salivary CYFRA 21-1 to have superior sensitivity in detecting OSCC compared with serum CYFRA 21-1. CONCLUSIONS: The outcome of this study suggests that salivary CYFRA 21-1 can be utilized as a biomarker in early detection of oral cancer.

Validation of the diagnostic utility of salivary interleukin 8 in the differentiation of potentially malignant oral lesions and oral squamous cell carcinoma in a region with high endemicity.

OBJECTIVE: To evaluate the clinical utility of salivary interleukin 8 (IL-8) in the differential diagnosis of potentially malignant lesions (PMLs) and oral squamous cell carcinoma (OSCC) in a region with high oral cancer prevalence. STUDY DESIGN: Saliva and blood samples were collected from 100 participants in each group (OSCC, PMLs, and healthy controls). Serum and salivary IL-8 levels were measured by enzyme-linked immunosorbent assay. The data were subjected to appropriate statistical analysis. RESULTS: A significant increase in levels of serum and salivary IL-8 was found in OSCC compared with PMLs and healthy controls. Receiver operating characteristic curve analysis found salivary IL-8 to have superior sensitivity in detecting OSCC. A significant increase in IL-8 levels based on the histologic grading of OSCC was also observed. CONCLUSIONS: This study confirms that salivary IL-8 can be a potent marker that can be used as a tool in the differential diagnosis of PMLs and OSCC.

The chemosensitizing activity of inhibitors of glucosylceramide synthase is mediated primarily through modulation of P-gp function.

Glucosylceramide synthase (GCS) is a key enzyme engaged in the biosynthesis of glycosphingolipids and in regulating ceramide metabolism. Studies exploring alterations in GCS activity suggest that the glycolase may have a role in chemosensitizing tumor cells to various cancer drugs. The chemosensitizing effect of inhibitors of GCS (e.g. PDMP and selected analogues) has been observed with a variety of tumor cells leading to the proposal that the sensitizing activity of GCS inhibitors is primarily through increases in intracellular ceramide leading to induction of apoptosis. The current study examined the chemosensitizing activity of the novel GCS inhibitor, Genz-123346 in cell culture. Exposure of cells to Genz-123346 and to other GCS inhibitors at non-toxic concentrations can enhance the killing of tumor cells by cytotoxic anti-cancer agents. This activity was unrelated to lowering intracellular glycosphingolipid levels. Genz-123346 and a few other GCS inhibitors are substrates for multi-drug resistance efflux pumps such as P-gp (ABCB1, gP-170). In cell lines selected to over-express P-gp or which endogenously express P-gp, chemosensitization by Genz-123346 was primarily due to the effects on P-gp function. RNA interference studies using siRNA or shRNA confirmed that lowering GCS expression in tumor cells did not affect their responsiveness to commonly used cytotoxic drugs.

Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence.

The PSMD14 (POH1, also known as Rpn11/MPR1/S13/CepP1) protein within the 19S complex (19S cap; PA700) is responsible for substrate deubiquitination during proteasomal degradation. The role of PSMD14 in cell proliferation and senescence was explored using siRNA knockdown in carcinoma cell lines. Our results reveal that down-regulation of PSMD14 by siRNA transfection had a considerable impact on cell viability causing cell arrest in the G0-G1 phase, ultimately leading to senescence. The molecular events associated with decreased cell proliferation, cell cycle arrest and senescence include down-regulation of cyclin B1-CDK1-CDC25C, down-regulation of cyclin D1 and up-regulation of p21(/Cip) and p27(/Kip1). Most notably, phosphorylation of the retinoblastoma protein was markedly reduced in PSMD14 knockdown cells. A comparative study with PSMB5, a subunit of the 20S proteasome, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events. These data support the view that the 19S and 20S subunits of the proteasome have distinct biological functions and imply that targeting 19S and 20S would have distinct molecular consequences on tumor cells.

Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) is often associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects. Phenotypic analysis revealed a defective differentiation of MoDC in PTB patients as assessed by a strong down regulation of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was not affected and remained same as in healthy subjects. Furthermore, the maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in PTB. However, the MoDC of PTB patients produced significantly higher levels of TNF-alpha and IL-6 but lower levels of IL-12 compared to healthy subjects. These findings suggest that there is a fundamental defect in the differentiation and maturation of dendritic cells during PTB that may compromise the antigen presentation and subsequent immune functions.

Differential migration of human monocyte-derived dendritic cells after infection with prevalent clinical strains of Mycobacterium tuberculosis.

Dendritic cells (DCs) play a key role in the host immune response to infections. Mycobacterium tuberculosis (MTB) can inhibit the maturation of DCs and impair their ability to stimulate T cell proliferation. Here, we assessed in vitro migratory behavior of human monocyte-derived DCs (MoDC) when infected with various MTB strains (H37Rv and prevalent clinical strains S7 and S10 from South India). The migration of Rv and S7 infected MoDC towards secondary lymphoid chemokine (CCL21) was 50% lower after 1 day of infection compared to LPS stimulation. This reduced cell migration may be due to a block in the chemokine receptor switch from CCR5 to CCR7 expression on MoDC. Only clinical strain S10 infected MoDC showed an up-regulation of CCR7 and down-regulation of CCR5 expression, similar to LPS stimulated MoDC. While Rv and S7 infected MoDC did not display any alteration in expression of these receptors. Similarly, Rv and S7 infected MoDC did not induce IL-8, IP-10 and MCP-1 chemokine production. This reduction in chemokine levels was reflected in the reduced chemoattraction of CD4(+) T cells also. These findings suggest that there is variation in the stimulation of MoDC with different clinical strains of MTB and this variation may be dependent upon the virulence of the strain.

Infection with prevalent clinical strains of Mycobacterium tuberculosis leads to differential maturation of monocyte derived dendritic cells.

The link between innate and adaptive host immune response to Mycobacterium tuberculosis (M.tb) is driven by dendritic cells (DC). In this study, we examined the ability of prevalent clinical strains from south India (S7, S10) and laboratory strain H37Rv (Rv) to induce maturation of monocyte derived dendritic cells (MoDC). The phenotypic and functional changes of DC upon infection with different strains of M.tb were evaluated. It was observed that S7 and Rv strains partially hampered the maturation of MoDC as reflected by the low expression of maturation markers and co-stimulatory markers when compared to LPS stimulated MoDC. In contrast, strain S10 infected DC showed a marked increase in the expression of these markers. The functional property was investigated by the ability of infected MoDC to induce T-cell proliferation and to stimulate secretion of IFN-gamma by CD4(+)T-cells. It was found that Rv and S7 infected MoDC were less efficient in inducing T-cell proliferation. The secretion of IL-12 by Rv and S7 infected MoDC was also found to be significantly lesser than LPS stimulated MoDC. On the other hand, S10 infected MoDC showed enhanced T-cell stimulation and cytokine secretion. Together these results indicate that there is a substantial variability in the capacity of M.tb clinical strains to induce maturation of DC which may be dependent upon their virulence.

TLR2 and TLR4 expression on the immune cells of tuberculous pleural fluid.

Toll-like receptors (TLRs) play an important role in mediating the down stream signaling of immune response in tuberculosis. The predominance of Th1 response in tuberculous pleurisy prompted us to study the expression profiles of TLR2 and TLR4 on different immune cells and on subsets of T cells obtained from the site of infection. Our results showed that TLR2 was up-regulated on the monocytes from pleural fluid indicating a prominent role for this receptor in anti-tuberculous immunity. Notably, TLR2 and TLR4 expression were also enhanced on IFN-gamma secreting CD4(+)T cells. However, their expression was down-regulated on activated and IL-4 secreting CD4(+)T cells from the site of infection indicating that TLR expression is differentially modulated on the different subsets of T cells depending on their activation status and cytokine expression. The down-regulation of both TLRs on the natural regulatory T cells despite their higher number at the site of infection might be a mechanism to maintain their suppressive activity.

Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.

BACKGROUND: A major focus of prostate cancer research has been to identify genes that are deregulated during tumor progression, potentially providing diagnostic markers and therapeutic targets. METHODS: We have employed serial analysis of gene expression (SAGE) and microarray hybridization to identify alterations that occur during malignant transformation in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. Many of these alterations were validated by real-time PCR (rtPCR). RESULTS: We identified several hundred mRNAs that were deregulated. Cluster analysis of microarray profiles with samples from various stages of the disease demonstrated that androgen-independent (AI) primary tumors are similar to metastases; 180 transcripts have expression patterns suggesting an involvement in the genesis of late-stage tumors, and our data support a role for phospholipase A2 group IIA in the acquisition of their highly aggressive characteristics. CONCLUSIONS: Our analyses identified well-characterized genes that were previously known to be involved in prostate cancer, validating our study, and also uncovered transcripts that had not previously been implicated in prostate cancer progression.