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Find video protocols related to scientific articles indexed in Pubmed.
Inflammatory Myofibroblastic Tumor of the Urinary Bladder: The Role of IgG4 and the Comparison of Two Immunohistochemical Antibodies and Fluorescence in Situ Hybridization for the Detection of ALK Alterations.
Histopathology
PUBLISHED: 11-20-2014
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We examined gene rearrangement and the expression of anaplastic lymphoma kinase (ALK) in urinary bladder inflammatory myofibroblastic tumor (IMT) using fluorescence in situ hybridization (FISH) and two immunohistochemical antibodies to ALK. We also investigated whether IMT represents an IgG4-related disease.
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Small cell carcinoma of the prostate: Molecular basis and clinical implications.
Histol. Histopathol.
PUBLISHED: 11-11-2014
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Small cell carcinoma of the prostate (PSCC) is a rare and highly aggressive malignancy with a dismal prognosis. Most patients present with advanced disease, including metastases to bone, viscera, and the central nervous system. Histologically, PSCC is indistinguishable from its pulmonary counterpart. Although PSCC may occur in pure form, as in small cell lung carcinoma, it also occurs in conjunction with conventional glandular prostate carcinoma, and may evolve from conventional adenocarcinoma during the course of hormonal therapy. Immunohistochemical staining is extremely helpful in establishing the diagnosis, a prerequisite, as in small cell lung cancer, for optimal therapeutic strategy. Currently, combinations of surgical resection, chemotherapy, and radiation therapy represent the main treatment options. Improvement in survival may depend upon the identi?cation of new molecular markers to facilitate earlier diagnosis and the development of novel targeted therapies. This review will discuss general aspects of PSCC, focusing on ways in which our understanding of PSCC has been advanced by studies of the histopathologic, immunohistochemical and molecular alterations in this disease.
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[System of ns time-resolved spectroscopy diagnosis and radioprotection].
Guang Pu Xue Yu Guang Pu Fen Xi
PUBLISHED: 11-01-2014
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Cathode plasma of high current electron beam diode is an important research on high power microwave and strong pulsed radio accelerator. It is a reliable method to study cathode plasma by diagnosing the cathode plasma parameters with non-contact spectroscopy measurement system. The present paper introduced the work principle, system composition and performance of the nanosecond (ns) time-resolved spectroscopy diagnosis system. Furthermore, it introduced the implementing method and the temporal relation of lower jitter synchronous trigger system. Simultaneously, the authors designed electromagnetic and radio shield room to protect the diagnosis system due to the high electromagnetic and high X-ray and ?-ray radiation, which seriously interferes with the system. Time-resolved spectroscopy experiment on brass (H62) cathode shows that, the element and matter composition of cathode plasma is clearly increase with the increase in the diode pulsed voltage and current magnitude. The spectroscopy diagnosis system could be of up to 10 ns time resolve capability. It's least is 2 ns. Synchronous trigger system's jitter is less than 4 ns. The spectroscopy diagnosis system will open a new way to study the cathode emission mechanism in depth.
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Surgical Correction of Anomalous Origin of One Pulmonary Artery Without Grafts in Infants.
J Card Surg
PUBLISHED: 10-21-2014
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To review the experiences in repairing the anomalous origin of one pulmonary artery in infants.
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Prostate changes related to therapy: with special reference to hormone therapy.
Future Oncol
PUBLISHED: 10-18-2014
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ABSTRACT? Hormone and radiation therapy have traditionally been used in prostate cancer (PCa). Morphological effects are often identified in needle biopsies and surgical specimens. A range of histological changes are seen in the non-neoplastic prostate and in the pre-neoplastic and neoplastic areas. Other ablative therapies, including cryotherapy, and emerging focal therapies, such as high-intensity focused ultrasound, photodynamic therapy and interstitial laser thermotherapy, may induce changes on the prostate. As new compounds are developed for prostate cancer treatment, it is important to document their effects on benign and neoplastic prostate tissue.
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Renal cell carcinoma with angioleiomyoma-like stroma: clinicopathological, immunohistochemical, and molecular features supporting classification as a distinct entity.
Mod. Pathol.
PUBLISHED: 09-05-2014
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Rare renal epithelial neoplasms have been recognized to have an angioleiomyoma or leiomyoma-like proliferation of stromal smooth muscle; however, the nature of these tumors and their relationships to other renal cell carcinomas are poorly understood. We analyzed 23 such tumors for their clinicopathological, immunohistochemical, and cytogenetic features using fluorescence in situ hybridization. Twelve showed a homogeneous combination of features and were reclassified as renal cell carcinoma with angioleiomyoma-like stroma. These were composed of neoplastic glandular structures lined by cells with mixed clear, pale, and eosinophilic cytoplasm forming occasional papillary tufts. The stroma resembled smooth muscle and often extended away from the epithelial component, entrapping perinephric fat or non-neoplastic renal elements. Immunohistochemistry showed the epithelium to have reactivity for: carbonic anhydrase IX, CD10, vimentin, cytokeratin 7, cytokeratin 34?E12, and PAX8 but not ?-methylacyl-coA-racemase. The stroma labeled for smooth muscle (smooth muscle actin 3+, desmin 1+, caldesmon 3+) but not epithelial antigens. Neither component showed substantial reactivity for HMB45, melan-A, cathepsin K, or TFE3 protein. An interrupted, conspicuous layer of CD34-positive endothelial cells rimmed the epithelium, imparting a two-cell layer pattern resembling myoepithelial or basal cells. Chromosome 3p deletion and trisomy 7 and 17 were uniformly absent. Follow-up was available for three patients, none of whom experienced malignant behavior. Eleven tumors were excluded from this category and considered to be clear cell renal cell carcinoma with a reactive proliferation of smooth muscle (n=4) or tangential sectioning of the pseudocapsule (n=2), renal cell carcinoma unclassified (n=4), or clear cell papillary renal cell carcinoma (n=1). In summary, renal cell carcinoma with angioleiomyoma-like stroma is a distinct neoplasm with characteristic morphological, immunohistochemical, and molecular features, unrelated to clear cell renal cell carcinoma. The immunoprofile overlaps partly with that of clear cell papillary renal cell carcinoma, though morphology and reactivity for CD10 are points of contrast.Modern Pathology advance online publication, 5 September 2014; doi:10.1038/modpathol.2014.105.
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Quantitative score modulation of HSP90 and HSP27 in clear cell renal cell carcinoma.
Pathology
PUBLISHED: 09-05-2014
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We sought to evaluate the expression of HSP27 and HSP90 chaperones in renal cell carcinomas as a target for cancer therapeutics.A total of 127 clear cell renal cell carcinomas stratified according to the Mayo Clinic SSIGN (size, staging, grading, and necrosis) risk groups (good, 1; poor, 5) and 20 cases with metastases, were available. Immunostaining for both HSP27 and HSP90 was performed on tissue microarrays. Results were detailed per scorable arrays per SSIGN risk groups.Immunolabelling for HSP90 and HSP27 was seen in 109 of 127 (86%) and 114 of 127 (89%) cases, respectively. HSP90 scored 4.9 in 32 cases risked SSIGN 1, 3.5 in 41 cases SSIGN 2, 4.8 in 11 cases SSIGN 3, 4.2 in 22 cases SSIGN 4, and 5.0 in three cases SSIGN 5. HSP27 scored 4.6 in 33 risked SSIGN 1, 3.1 in 43 SSIGN 2, 2.6 in 11 SSIGN 3, 3.6 in 24 SSIGN 4, and 2.7 in three SSIGN 5. Metastases ranged from 2.9-5.0. A trend of increasing value for HSP90 was observed when comparing SSIGN 1-2 versus SSIGN 3-5 risk groups (4.2 versus 4.6 mean values; p?=?0.06); no difference has been observed for HSP27 (3.8 to 3.9; p?=?0.08).A score modulation of HSPs is observed in renal cell carcinoma and may affect the efficacy of targeted therapy.
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GATA-3 Expression in Trophoblastic Tissues: An Immunohistochemical Study of 445 Cases, Including Diagnostic Utility.
Am. J. Surg. Pathol.
PUBLISHED: 09-03-2014
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Immunohistochemical expression of GATA-3 is seen predominantly in non-neoplastic bladder and breast epithelium and their respective carcinomas; however, data on expression in normal and lesional trophoblastic tissues are limited. Immunohistochemical staining for GATA-3 was assessed in a range of normal/lesional trophoblastic tissues and tumors in the differential diagnosis (n=445), including nonmolar products of conceptions/second and third trimester placentas/ectopic pregnancies, hydatidiform moles, placental site nodules, normal/exaggerated implantation sites, choriocarcinomas, epithelioid trophoblastic tumors, placental site trophoblastic tumors, atypical smooth muscle tumors (including leiomyosarcoma), and cervical and pulmonary squamous cell carcinomas. The extent of expression (0 to 4+) and intensity (weak to strong) were recorded. All cases with developing trophoblast/non-neoplastic trophoblastic proliferation and 81% of trophoblastic neoplasms were positive. Of all non-neoplastic trophoblast cell types, expression was observed in cytotrophoblast in 89% of cases, syncytiotrophoblast in 50%, intermediate trophoblast in 100%, and villous trophoblastic columns in 100%. Increasing gestational age was associated with a decrease in extent/intensity of expression in non-neoplastic cytotrophoblast and syncytiotrophoblast, whereas intermediate trophoblast maintained diffuse and strong expression from early to late gestation (P<0.0001). Eighty-nine percent of normal/exaggerated implantation sites showed 3+ or 4+ expression, whereas staining in 55% of placental site nodules was 1+ or 2+. Staining for GATA-3 was present in 78% of choriocarcinomas, 95% of epithelioid trophoblastic tumors, and 71% of placental site trophoblastic tumors. Although the number of choriocarcinomas and placental site trophoblastic tumors that showed a spectrum of expression ranging from negative to diffuse was relatively evenly distributed, 81% of epithelioid trophoblastic tumors had 3+ or 4+ staining. None of the atypical smooth muscle tumors and 3% of squamous cell carcinomas were positive, all of which exhibited weak staining. We conclude that GATA-3 is frequently expressed in normal and lesional trophoblastic tissues. It is also differentially expressed in intermediate trophoblast and cytotrophoblast/syncytiotrophoblast, which varies according to time during pregnancy. This study expands the spectrum of neoplasms known to express GATA-3. Thus, recognition of expression in trophoblastic tumors is important, because it can present a diagnostic pitfall in the assessment of suspected metastatic bladder or breast carcinomas involving the gynecologic tract. In the evaluation of diagnostically problematic tumors for which trophoblastic neoplasms are in the differential diagnosis, such as leiomyosarcoma and squamous cell carcinoma, GATA-3 can be included as part of an immunohistochemical panel particularly when other trophoblastic markers are either not available or yield ambiguous results.
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Intraductal carcinoma of the prostate: interobserver reproducibility survey of 39 urologic pathologists.
Ann Diagn Pathol
PUBLISHED: 08-26-2014
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The diagnosis of intraductal carcinoma (IDC) of the prostate remains subjective because 3 sets of diagnostic criteria are in use. An internet survey was compiled from 38 photomicrographs showing duct proliferations: 14 signed out as high-grade prostatic intraepithelial neoplasia (HGPIN), 17 IDC, and 7 invasive cribriform/ductal carcinoma. Each image was assessed for the presence of 9 histologic criteria ascribed to IDC. Thirty-nine respondents were asked to rate images as (1) benign/reactive, (2) HGPIN, (3) borderline between HGPIN and IDC, (4) IDC, or (5) invasive cribriform/ductal carcinoma. Intraclass correlation coefficient was 0.68. There was 70% overall agreement with HGPIN, 43% with IDC, and 73% with invasive carcinoma (P < .001, ?(2)). Respondents considered 19 (50%) of 38 cases as IDC candidates, of which 5 (26%) had a two-thirds consensus for IDC; two-thirds consensus for either borderline or IDC was reached in 9 (47%). Two-thirds consensus other than IDC was reached in the remaining 19 of 38 cases, with 15 supporting HGPIN and 4 supporting invasive carcinoma. Findings that differed across diagnostic categories were lumen-spanning neoplastic cells (P < .001), 2× benign duct diameters (P < .001), duct space contours (round, irregular, and branched) (P < .001), papillary growth (P = .048), dense cribriform or solid growth (both P = .023), and comedonecrosis (P = .015). When the 19 of 38 images that attained consensus for HGPIN or invasive carcinoma were removed from consideration, lack of IDC consensus was most often attributable to only loose cribriform growth (5/19), central nuclear maturation (5/19), or comedonecrosis (3/19). Of the 9 histologic criteria, only 1 retained significant correlation with a consensus diagnosis of IDC: the presence of solid areas (P = .038). One case that attained IDC consensus had less than 2× duct enlargement yet still had severe nuclear atypia and nucleomegaly. Six fold nuclear enlargement was not significant (P = .083), although no image had both 6× nuclei and papillary or loose cribriform growth: a combination postulated as sufficient criteria for IDC. Finally, 20.5% of respondents agreed that an isolated diagnosis of IDC on needle biopsy warrants definitive therapy, 20.5% disagreed, and 59.0% considered the decision to depend upon clinicopathologic variables. Although IDC diagnosis remains challenging, we propose these criteria: a lumen-spanning proliferation of neoplastic cells in preexisting ducts with a dense cribriform or partial solid growth pattern. Solid growth, in any part of the duct space, emerges as the most reproducible finding to rule in a diagnosis of IDC. Comedonecrosis is a rarer finding, but in most cases, it should rule in IDC. Duct space enlargement to greater than 2× the diameter of the largest, adjacent benign spaces is usually present in IDC, although there may be rare exceptions.
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Does prostate acinar adenocarcinoma with Gleason Score 3¿+¿3¿=¿6 have the potential to metastasize?
Diagn Pathol
PUBLISHED: 08-22-2014
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BackgroundThere is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer.Case descriptionWe report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3¿+¿3¿=¿6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (<5% of the whole tumor) of Gleason pattern 4 (poorly formed glands) was found in an extraprostatic position.ConclusionThe epilogue was that the additional finding changed the final Gleason score to 3¿+¿3¿=¿6 with tertiary pattern 4 and the stage to pT3a.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_190.
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PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy.
Biomaterials
PUBLISHED: 08-22-2014
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Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T1-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy.
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cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles for targeted chemotherapy of glioblastoma in vivo.
J Control Release
PUBLISHED: 08-07-2014
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cRGD-directed, NIR-responsive and robust AuNR/PEG-PCL hybrid nanoparticles (cRGD-HNs) were designed and developed for targeted chemotherapy of human glioma xenografts in mice. As expected, cRGD-HNs had excellent colloidal stability. The in vitro release studies showed that drug release from DOX-loaded cRGD-HNs (cRGD-HN-DOX) was minimal under physiological conditions but markedly accelerated upon NIR irradiation at a low power density of 0.2W/cm(2), due to photothermally induced phase transition of PCL regime. MTT assays showed that the antitumor activity of cRGD-HN-DOX in ?v?3 integrin over-expressed human glioblastoma U87MG cells was greatly boosted by mild NIR irradiation, which was significantly more potent than non-targeting HN-DOX counterpart under otherwise the same conditions and was comparable or superior to free DOX, supporting receptor-mediated endocytosis mechanism. The in vivo pharmacokinetics studies showed that cRGD-HN-DOX had much longer circulation time than free DOX. The in vivo imaging and biodistribution studies revealed that cRGD-HN-DOX could actively target human U87MG glioma xenograft in nude mice. The therapeutic studies in human U87MG glioma xenografts exhibited that cRGD-HN-DOX in combination with NIR irradiation completely inhibited tumor growth and possessed much lower side effects than free DOX. The Kaplan-Meier survival curves showed that all mice treated with cRGD-HN-DOX plus NIR irradiation survived over an experimental period of 48days while control groups treated with PBS, cRGD-HN-DOX, cRGD-HNs with NIR irradiation, free DOX, or HN-DOX with NIR irradiation (non-targeting control) had short life spans of 15-40days. Ligand-directed AuNR/PEG-PCL hybrid nanoparticles with evident tumor-targetability as well as superior spatiotemporal and rate control over drug release have emerged as an appealing platform for cancer chemotherapy in vivo.
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On the pathogenesis of sclerosing stromal tumor of the ovary: a neoplasm in transition.
Int. J. Gynecol. Pathol.
PUBLISHED: 08-02-2014
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Sclerosing stromal tumor (SST) is a distinctive benign ovarian stromal neoplasm first reported in 1973. Although its initial description supports its characterization as an ovarian stromal tumor, its exact pathogenesis remains uncertain. It is usually hormonally inactive, but occasional tumors are estrogenic or androgenic, and virilization can occur during pregnancy. We report 11 cases of SST, 6 of which were associated with another type or other types of ovarian stromal tumor. In 4 of these, a transition from thecoma of either typical or luteinized type to SST was observed. Our index case was that of a 16-yr-old girl who had a typical thecoma that underwent involutional changes in an extensive subserosal portion of the tumor with conversion to SST. In our series, 3 cases of SST underwent transformation to ovarian myxoma, one of which also contained a component of thecoma. The active SST components stained for inhibin, steroidogenic factor 1, and ?-smooth muscle actin, but were negative or occasionally weakly positive for desmin.
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qPCR is a sensitive and rapid method for detection of cytomegaloviral DNA in formalin-fixed, paraffin-embedded biopsy tissue.
J Vis Exp
PUBLISHED: 07-22-2014
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It is crucial to identify cytomegalovirus (CMV) infection in the gastrointestinal (GI) tract of immunosuppressed patients, given their greater risk for developing severe infection. Many laboratory methods for the detection of CMV infection have been developed, including serology, viral culture, and molecular methods. Often, these methods reflect systemic involvement with CMV and do not specifically identify local tissue involvement. Therefore, detection of CMV infection in the GI tract is frequently done by traditional histology of biopsy tissue. Hematoxylin and eosin (H&E) staining in conjunction with immunohistochemistry (IHC) have remained the mainstays of examining these biopsies. H&E and IHC sometimes result in atypical (equivocal) staining patterns, making interpretation difficult. It was shown that quantitative polymerase chain reaction (qPCR) for CMV can successfully be performed on formalin-fixed, paraffin-embedded (FFPE) biopsy tissue for very high sensitivity and specificity. The goal of this protocol is to demonstrate how to perform qPCR testing for the detection of CMV in FFPE biopsy tissue in a clinical laboratory setting. This method is likely to be of great benefit for patients in cases of equivocal staining for CMV in GI biopsies.
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Total submission of lymphadenectomy tissues removed during radical prostatectomy for prostate cancer: possible clinical significance of large-format histology.
Hum. Pathol.
PUBLISHED: 07-17-2014
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Complete submission of lymphadenectomy specimens increases the number of recovered lymph nodes and the detection of metastatic disease. There are advantages with the whole-mount technique over complete sampling with standard cassettes in terms of time needed to sample the tissue, number of blocks to be cut, and slides to be examined. The clinical significance of the approach is that all lymph nodes are identified, including those that are not palpable. In particular, this approach avoids the fact that an individual lymph node is oversampled and counted according to number of pieces obtained by the pathologist, mainly in nodes with considerable size.
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Enhanced effect of pH-sensitive mixed copolymer micelles for overcoming multidrug resistance of doxorubicin.
Biomaterials
PUBLISHED: 07-04-2014
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P-glycoprotein (P-gp) mediated drug efflux has been recognized as a key factor contributing to the multidrug resistance (MDR) in tumor cells. To address this issue, a new pH-sensitive mixed copolymer micelles system composed of hyaluronic acid-g-poly(l-histidine) (HA-PHis) and d-?-tocopheryl polyethylene glycol 2000 (TPGS2k) copolymers was developed to co-deliver doxorubicin (DOX) and TPGS2k into drug-resistant breast cancer MCF-7 cells (MCF-7/ADR). The DOX-loaded HA-PHis/TPGS2k mixed micelles (HPHM/TPGS2k) were characterized to have a unimodal size distribution, high DOX loading content and a pH dependent drug release profile due to the protonation of poly(l-histidine). As compared to HA-PHis micelles (HPHM), the HPHM/TPGS2k showed higher and comparable cytotoxicity against MCF-7/ADR cells and MCF-7 cells, respectively. The enhanced MDR reversal effect was attributed to the higher amount of cellular uptake of HPHM/TPGS2k in MCF-7/ADR cells than HPHM, arising from the inhibition of P-gp mediated drug efflux by TPGS2k. The measurements of P-gp expression level and mitochondrial membrane potential indicate that the blank HPHM/TPGS2k inhibited P-gp activity by reducing mitochondrial membrane potential and depletion of ATP but without inhibition of P-gp expression. In vivo study of micelles in tumor-bearing mice indicate that HPHM/TPGS2k could reach the tumor site more effectively than HPHM. The pH-sensitive mixed micelles system has been demonstrated to be a promising approach for overcoming the MDR.
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Near-infrared light triggered photodynamic therapy in combination with gene therapy using upconversion nanoparticles for effective cancer cell killing.
Nanoscale
PUBLISHED: 07-02-2014
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Upconversion nanoparticles (UCNPs) have drawn much attention in cancer imaging and therapy in recent years. Herein, we for the first time report the use of UCNPs with carefully engineered surface chemistry for combined photodynamic therapy (PDT) and gene therapy of cancer. In our system, positively charged NaGdF4:Yb,Er UCNPs with multilayered polymer coatings are synthesized via a layer by layer strategy, and then loaded simultaneously with Chlorin e6 (Ce6), a photosensitizing molecule, and small interfering RNA (siRNA), which targets the Plk1 oncogene. On the one hand, under excitation by a near-infrared (NIR) light at 980 nm, which shows greatly improved tissue penetration compared with visible light, cytotoxic singlet oxygen can be generated via resonance energy transfer from UCNPs to photosensitizer Ce6, while the residual upconversion luminescence is utilized for imaging. On the other hand, the silencing of Plk1 induced by siRNA delivered with UCNPs could induce significant cancer cell apoptosis. As the result of such combined photodynamic and gene therapy, a remarkably enhanced cancer cell killing effect is realized. Our work thus highlights the promise of UCNPs for imaging guided combination therapy of cancer.
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Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice.
PLoS Pathog.
PUBLISHED: 07-01-2014
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The role of plasmacytoid dendritic cells (pDC) in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I) induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs) were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment.
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A newly developed uroplakin II antibody with increased sensitivity in urothelial carcinoma of the bladder.
Arch. Pathol. Lab. Med.
PUBLISHED: 07-01-2014
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Uroplakin II is a 15-kDa protein component of the urothelial plaques that enhance the permeability barrier and strength of the urothelium. Studies have shown uroplakin II messenger RNA to be expressed in bladder cancer tissues and peripheral blood of patients with urothelial carcinoma. Little is known about the protein expression of uroplakin II in urothelial carcinoma, possibly because of the absence of a commercially available uroplakin II antibody. Pathologists have used the uroplakin III antibody (AU1) to identify tumors of urothelial origin; however, the use of AU1 is limited because of its poor sensitivity.
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Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1.
J. Pineal Res.
PUBLISHED: 06-10-2014
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Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl-2 expression and downregulating Bax, caspase-3 and cleaved caspase-3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91(phox) expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R-induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor-dependent manner.
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A synthetic method for atmospheric diffusion simulation and environmental impact assessment of accidental pollution in the chemical industry in a WEBGIS context.
Int J Environ Res Public Health
PUBLISHED: 06-09-2014
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The chemical industry poses a potential security risk to factory personnel and neighboring residents. In order to mitigate prospective damage, a synthetic method must be developed for an emergency response. With the development of environmental numeric simulation models, model integration methods, and modern information technology, many Decision Support Systems (DSSs) have been established. However, existing systems still have limitations, in terms of synthetic simulation and network interoperation. In order to resolve these limitations, the matured simulation model for chemical accidents was integrated into the WEB Geographic Information System (WEBGIS) platform. The complete workflow of the emergency response, including raw data (meteorology information, and accident information) management, numeric simulation of different kinds of accidents, environmental impact assessments, and representation of the simulation results were achieved. This allowed comprehensive and real-time simulation of acute accidents in the chemical industry. The main contribution of this paper is that an organizational mechanism of the model set, based on the accident type and pollutant substance; a scheduling mechanism for the parallel processing of multi-accident-type, multi-accident-substance, and multi-simulation-model; and finally a presentation method for scalar and vector data on the web browser on the integration of a WEB Geographic Information System (WEBGIS) platform. The outcomes demonstrated that this method could provide effective support for deciding emergency responses of acute chemical accidents.
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Contemporary update on pathology-related issues of adult renal neoplasms.
Anal Quant Cytopathol Histpathol
PUBLISHED: 06-07-2014
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This review gives an update on selected issues on renal neoplasia with special references to emerging new tumor entities (thyroid-like follicular renal cell carcinoma, succinic dehydrogenase B deficiency-associated renal cell carcinoma, and anaplastic lymphoma kinase [ALK] translocation renal cell carcinoma), tumor grading (the International Society of Urological Pathology grading system), and assessment of tumoral involvement of the renal sinus structures, including the sinus fat, the loose connective tissue, or any sinus-based endothelium-lined space.
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Contemporary update on pathology-related issues on routine workup of prostate biopsy: sectioning, tumor extent measurement, specimen orientation, and immunohistochemistry.
Anal Quant Cytopathol Histpathol
PUBLISHED: 06-07-2014
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While the prime goal of the needle biopsy is to diagnose prostatic adenocarcinoma (PCa), once PCa is detected further descriptive information regarding the type of cancer, amount of tumor, and grade in prostate needle cores forms the cornerstone for contemporary management of the patient and to assess the potential for local cure and the risk for distant metastasis. This review gives an update on selected pathology-related issues on routine workup of prostate biopsy with special references to adequate histologic sectioning necessary to maximize cancer yield, tumor extent measurements and methodologies, specimen orientation, and the role of immunohistochemistry in the evaluation of the prostate. Multiple factors influence the diagnostic yield of prostate biopsies. Many of these factors are fixed and uncontrollable. Other factors are controlled by the urologist, including number of cores obtained, method and location of biopsy, and amount of tissue obtained. The yield of cancer is also controlled by the pathologist and histotechnologist. It is necessary to report the number of cores submitted and the number of positive cores, thereby giving the fraction of positive cores. The percentage involvement by carcinoma with or without the linear extent of carcinoma of the single core with the greatest amount of tumor should also be provided. Using the marking technique, we can add a new pathological parameter: pathological orientation. Cancer or atypical lesions can be accurately located within the biopsy specimen and integrated to biopsy approach. Probably the most common use of immunohistochemistry in the evaluation of the prostate is for the identification of basal cells, which are absent with rare exception in adenocarcinoma of the prostate and in general positive in mimickers of prostate cancer. If a case is still considered atypical by a uropathology expert after negative basal cell staining, positive staining for alpha-methylacyl-CoA-racemase can help establish in 50% of these cases a definitive diagnosis of cancer.
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Detection of BRAF Mutation in Metastatic Melanoma Utilizing Cell-Transferred Cytological Smears.
Acta Cytol.
PUBLISHED: 06-04-2014
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Objectives: Fine-needle aspiration (FNA) is frequently used to diagnose metastatic melanoma. In this study, we validated the use of cell-transferred cytological smears for BRAF molecular testing. Study Design: We conducted a search of our laboratory information system for the period 2011-2013 in order to identify surgical pathology cases of either primary or metastatic melanomas in which BRAF mutation analyses had already been performed. Thirty FNA cases with diagnoses of metastatic melanoma from the same patients were identified. Direct smears from each FNA case were selected for mutation analyses using the cell transfer technique. Results: Mutation analyses were successfully performed on 28 of 30 FNA cases (93%) using the cell-transferred cytological smears. In 25 cases (8 BRAF mutations and 17 BRAF wild types), there was 100% agreement for the BRAF mutation between the cell-transferred cytological smears and the formalin-fixed paraffin-embedded tissues. Three FNA cases showed BRAF mutations that had not been detected in the correlated surgical specimens which were tested twice, and 2 cases failed to work. Conclusions: Cell-transferred cytological smears are a reliable and alternative resource for detecting BRAF mutations in metastatic melanoma. © 2014 S. Karger AG, Basel.
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Clinicopathological characteristics and outcome of nested carcinoma of the urinary bladder.
Virchows Arch.
PUBLISHED: 05-22-2014
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We present the clinicopathological features of 56 cases of the nested variant of urothelial bladder carcinoma. This is an uncommon variant of bladder cancer, recognized by the current WHO classification of urologic tumors. The nested component represented 100 % of the tumor in 24 cases. The architectural pattern of the tumor varied from solid expansile to infiltrative nests characterized by deceptively bland histologic features resembling von Brunn nests. Typical features of high-grade conventional urothelial carcinoma were present in 32 cases. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear enlargement, most frequently seen in deep areas of tumor. The nested component expressed cytokeratins 7, 20, CAM5.2, and high molecular weight (34ßE12), p63, Ki67, p53, p27, and GATA3. Tumor extension was T1 (n = 9), minimally T2 (n = 10), T2a (n = 1), T2b (n = 4), T3a (n = 8), T3b (n = 13), and T4a (n = 11). On follow-up, 36 of patients died of or were alive with disease from 2 to 80 months (mean 21 months). Four patients died of other causes. Eleven other patients remained disease free. Univariate survival analysis showed no differences for nested carcinoma compared with conventional urothelial carcinoma. As in conventional urothelial carcinoma, in nested carcinoma of the bladder pT category defined different survival groups. In summary, nested variant of urothelial bladder carcinoma is typically associated with advanced stage. In samples of limited volume, it may be misdiagnosed as proliferation of von Brunn nests or other nested-like bladder lesions, delaying definitive therapy.
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Deoxypolypeptides bind and cleave RNA.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-19-2014
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We have prepared L- and D-deoxypolypeptides (DOPPs) by selective reduction of appropriately protected polyhistidines with borane, reducing the carbonyl groups to methylenes. The result is a chiral polyamine, not amide, with a mainly protonated backbone and chirally mounted imidazolylmethylene side chains that are mostly unprotonated at neutrality because of the nearby polycationic backbone. We found that, in contrast with the D-octahistidine DOPP, the L-octahistidine DOPP is able to cooperatively bind to a D-polyuridylic acid RNA; this is consistent with results of previous studies showing that, relative to D-histidine, L-histidine is able to more strongly bind to RNA. The L-DOPP was also a better catalyst for cleaving the RNA than the D-DOPP, consistent with evidence that the L-DOPP uses its imidazole groups for catalysis, in addition to the backbone cations, but the D-DOPP does not use the imidazoles. The L-DOPP bifunctional process probably forms a phosphorane intermediate. This is a mechanism we have proposed for models of ribonuclease cleavage and for the ribonuclease A enzyme itself, based on our studies of the cleavage and isomerization of UpU catalyzed by imidazole buffers as well as other relevant studies. This mechanism contrasts with earlier, generally accepted ribonuclease cleavage mechanisms where the proton donor coordinates with the oxygen of the leaving group as the 2-hydroxyl of ribose attacks the unprotonated phosphate.
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Renal cell carcinoma in tuberous sclerosis complex.
Am. J. Surg. Pathol.
PUBLISHED: 05-17-2014
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Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term "TSC-associated papillary RCC (PRCC)." The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC.
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Graphene-based nanocomposite as an effective, multifunctional, and recyclable antibacterial agent.
ACS Appl Mater Interfaces
PUBLISHED: 05-15-2014
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The development of new antibacterial agents that are highly effective are of great interest. Herein, we present a recyclable and synergistic nanocomposite by growing both iron oxide nanoparticles (IONPs) and silver nanoparticles (AgNPs) on the surface of graphene oxide (GO), obtaining GO-IONP-Ag nanocomposite as a novel multifunctional antibacterial material. Compared with AgNPs, which have been widely used as antibacterial agents, our GO-IONP-Ag shows much higher antibacterial efficiency toward both Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphylococcus aureus (S. aureus). Taking the advantage of its strong near-infrared (NIR) absorbance, photothermal treatment is also conducted with GO-IONP-Ag, achieving a remarkable synergistic antibacterial effect to inhibit S. aureus at a rather low concentration of this agent. Moreover, with magnetic IONPs existing in the composite, we can easily recycle GO-IONP-Ag by magnetic separation, allowing its repeated use. Given the above advantages as well as its easy preparation and cheap cost, GO-IONP-Ag developed in this work may find potential applications as a useful antibacterial agent in the areas of healthcare and environmental engineering.
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Oncologic and quality-of-life outcomes with wide resection in robot-assisted laparoscopic radical prostatectomy.
Urol. Oncol.
PUBLISHED: 05-14-2014
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To assess urinary quality-of-life (QoL) and oncologic outcomes between wide resection (WR) robot-assisted laparoscopic radical prostatectomy (RALP) and non-WR (NWR) RALP in men with intermediate- or high-risk (Cancer of the Prostate Risk Assessment [CAPRA]-9 >2) prostate adenocarcinoma.
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Redox and pH-responsive poly (amidoamine) dendrimer-poly (ethylene glycol) conjugates with disulfide linkages for efficient intracellular drug release.
Colloids Surf B Biointerfaces
PUBLISHED: 04-24-2014
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Nanocarriers with low toxicity, high stability, long circulation in blood and triggered drug release at target sites are extremely needed for cancer therapy. In this study, different molar ratios of poly (ethylene glycol) (PEG) were conjugated to poly (amidoamine) dendrimer (PAMAM) by cleavable disulfide bonds, yielding redox and pH dual-responsive nanocarriers (PSSP). The redox sensitivity of the PSSP conjugates was confirmed by measuring the change in particle size and zeta potential under reductive environment by dynamic light scattering (DLS). Meanwhile, all conjugates showed slight hemolytic ratio and high stability in 10% FBS for 24h. Phagocytosis experiments indicated that the PSSP conjugates could effectively escape the engulfment of macrophage. Doxorubicin (DOX) was loaded into the hydrophobic core of the conjugates with loading content of 10%. In vitro release studies suggested that release rate as well as cumulative release amount of DOX from the PSSP conjugates were pronouncedly enhanced in reductive environment as compared with the non-cleavable counterparts. Besides, all conjugates exhibited excellent acid-triggered release performance. Significantly, PEGylation degree of the conjugates had critical impact on drug release. Cytotoxicity tests displayed that DOX-loaded PSSP conjugates were more potent in killing B16 and A549 tumor cells than the non-cleavable counterparts. Curiously, PSSP conjugate with the highest PEGylation degree showed the best antitumor effect despite the somewhat less cell uptake. Therefore, the dual-responsive PSSP conjugates seem promising candidates for efficient intracellular release of antitumor drugs.
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J-Aggregates of Organic Dye Molecules Complexed with Iron Oxide Nanoparticles for Imaging-Guided Photothermal Therapy Under 915-nm Light.
Small
PUBLISHED: 04-13-2014
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Recently, the development of nano-theranostic agents aiming at imaging guided therapy has received great attention. In this work, a near-infrared (NIR) heptamethine indocyanine dye, IR825, in the presence of cationic polymer, polyallylamine hydrochloride (PAH), forms J-aggregates with red-shifted and significantly enhanced absorbance. After further complexing with ultra-small iron oxide nanoparticles (IONPs) and the followed functionalization with polyethylene glycol (PEG), the obtained IR825@PAH-IONP-PEG composite nanoparticles are highly stable in different physiological media. With a sharp absorbance peak, IR825@PAH-IONP-PEG can serve as an effective photothermal agent under laser irradiation at 915 nm, which appears to be optimal in photothermal therapy application considering its improved tissue penetration compared with 808-nm light and much lower water heating in comparison to 980-nm light. As revealed by magnetic resonance (MR) imaging, those nanoparticles after intravenous injection exhibit high tumor accumulation, which is then harnessed for in vivo photothermal ablation of tumors, achieving excellent therapeutic efficacy in a mouse tumor model. This study demonstrates for the first time that J-aggregates of organic dye molecules are an interesting class of photothermal material, which when combined with other imageable nanoprobes could serve as a theranostic agent for imaging-guided photothermal therapy of cancer.
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Lymph node metastases in patients with urothelial carcinoma variants: Influence of the specific variant on nodal histology.
Urol. Oncol.
PUBLISHED: 04-12-2014
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The effect that the presence of urothelial variant (UV) histologies has on the behavior of urothelial carcinoma remains poorly defined. The goal of this study is to examine the relationship between different histologic variants and the presence and histology of lymph node metastases.
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Adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of spermatic cord leiomyosarcoma.
Diagn Pathol
PUBLISHED: 03-31-2014
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The aim of this report is related to adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of the spermatic cord leiomyosarcoma. Primary paratesticular tumors are rare, only accounting for 7% to 10% of all intrascrotal tumors. In adults, more than 75% of these lesions arise from the spermatic cord, 20% being leiomyosarcoma. Tumor grade, stage, histologic type, and lymph node involvement are independently predictive of prognosis.
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Clear Cell Renal Cell Carcinoma (ccRCC) with Hemangioblastoma-like Features: A Previously Unreported Pattern of ccRCC with Possible Clinical Significance.
Eur. Urol.
PUBLISHED: 03-23-2014
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The morphological features and immunohistochemical findings of two cases of clear cell renal cell carcinoma with extensive hemangioblastoma-like features are described. To the best of our knowledge, this is the first description of such a pattern, the differential diagnosis being with renal hemangioblastoma, a rare tumor that could be considered a diffuse hemangioblastoma-like change in a clear cell renal cell tumor. Even though the clinical significance and therapeutic implications are not yet known, the hemangioblastoma-like pattern could have favorable prognostic significance based on the fact that the renal hemangioblastomas described so far have benign behavior.
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Critical analysis of the 2010 TNM classification in patients with lymph node-positive bladder cancer: Influence of lymph node disease burden.
Urol. Oncol.
PUBLISHED: 02-28-2014
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In 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden.
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Recurrent papillary urothelial neoplasm of low malignant potential. Subtle architectural disorder detected by quantitative analysis in DAXX-immunostained tissue sections.
Hum. Pathol.
PUBLISHED: 02-26-2014
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The aim of the study was to identify subtle changes in the so-called architectural predominant order in nonrecurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). Quantitative analysis was performed with a software package written in LabVIEW (National Instruments, Austin, TX) in DAXX-immunostained tissue sections. Twelve cases of PUNLMP with papillary fronds sectioned lengthwise through the core were investigated and subdivided as follows: 7 nonrecurrent and 5 recurrent PUNLMP cases. Six cases of normal urothelium (NU) were included. When an epithelial thickness threshold is set at 108 ?m (ie, 400 pixels), there is a complete separation between NU and PUNLMP; however, nonrecurrent and recurrent cases fall in the same range of thickness. In setting a nuclear elongation factor threshold at 2.1, there are differences between the 2 PUNLMP groups, recurrent PUNLMP and NU cases, showing a somewhat similar proportion of elongated nuclei. The nuclear orientation separates nonrecurrent from recurrent PUNLMP groups; however, NU cases do not appear as a separate group from the 2 PUNLMP groups. In combining epithelial thickness, nuclear elongation, and orientation in a multivariate analysis, the 2 PUNLMP groups appear separate between them and from NU. NU is less thickened than the 2 PUNLMP groups and shows a combination of elongated and less elongated nuclei. Elongated nuclei are more numerous in nonrecurrent PUNLMP, whereas the nuclei in recurrent PUNLMP are less elongated and less polarized than in the other group. Such finding can be used routinely to identify those PUNLMP patients who will have recurrence.
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Discordancy in BRAF mutations among primary and metastatic melanoma lesions: clinical implications for targeted therapy.
Mod. Pathol.
PUBLISHED: 02-14-2014
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Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.Modern Pathology advance online publication, 7 November 2014; doi:10.1038/modpathol.2014.136.
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Plasmacytoid variant urothelial bladder cancer: is it time to update the treatment paradigm?
Urol. Oncol.
PUBLISHED: 02-12-2014
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Plasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC.
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Ultrathin WS2 nanoflakes as a high-performance electrocatalyst for the hydrogen evolution reaction.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-12-2014
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Much has been done to search for highly efficient and inexpensive electrocatalysts for the hydrogen evolution reaction (HER), which is critical to a range of electrochemical and photoelectrochemical processes. A new, high-temperature solution-phase method for the synthesis of ultrathin WS2 nanoflakes is now reported. The resulting product possesses monolayer thickness with dimensions in the nanometer range and abundant edges. These favorable structural features render the WS2 nanoflakes highly active and durable catalysts for the HER in acids. The catalyst exhibits a small HER overpotential of approximately 100?mV and a Tafel slope of 48?mV/decade. These ultrathin WS2 nanoflakes represent an attractive alternative to the precious platinum benchmark catalyst and rival MoS2 materials that have recently been heavily scrutinized for the electrocatalytic HER.
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Hexacyanoferrate-adapted biofilm enables the development of a microbial fuel cell biosensor to detect trace levels of assimilable organic carbon (AOC) in oxygenated seawater.
Biotechnol. Bioeng.
PUBLISHED: 02-11-2014
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A marine microbial fuel cell (MFC) type biosensor was developed for the detection of assimilable organic carbon (AOC) in ocean water for the purpose of online water quality monitoring for seawater desalination plants prone to biofouling of reverse osmosis (RO) membranes. The anodophilic biofilm that developed on the graphite tissue anode could detect acetate as the model AOC to concentrations as low as 5?µM (120?µg/L of AOC), which is sufficiently sensitive as an online biofouling risk sensor. Although the sensor was operated at a higher (+200?±?10?mV) than the usual (-300?mV) anodic potential, the presence of oxygen completely suppressed the electrical signal. In order to overcome this outcompeting effect of oxygen over the anode as electron acceptor by the bacteria, hexacyanoferrate (HCF(III)) was found to enable the development of an adapted biofilm that transferred electrons to HCF(III) rather than oxygen. As the resultant of the reduced HCF(II) could readily transfer electrons to the anode while being re-oxidised to HCF(III), the marine MFC biosensor developed could be demonstrated to work in the presence of oxygen unlike traditional MFC. The possibility of operating the marine MFC in batch or continuous (in-line) mode has been explored by using coulombic or potentiometric interpretation of the signal. Biotechnol. Bioeng. 2014;111: 2412-2420. © 2014 Wiley Periodicals, Inc.
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Folate and TAT Peptide Co-Modified Liposomes Exhibit Receptor-Dependent Highly Efficient Intracellular Transport of Payload In Vitro and In Vivo.
Pharm. Res.
PUBLISHED: 02-11-2014
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Using different chain lengths of PEG as linkers to develop a novel folate (FA) and TAT peptide co-modified doxorubicin (DOX)-loaded liposome (FA/TAT-LP-DOX) and evaluate its potential for tumor targeted intracellular drug delivery.
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Clear cell renal cell carcinoma with a syncytial-type multinucleated giant tumor cell component: implications for differential diagnosis.
Hum. Pathol.
PUBLISHED: 02-07-2014
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A component of syncytial-type multinucleated tumor giant cells is uncommon in clear cell renal cell carcinoma, and the histogenesis, incidence, and clinical implications of this finding are not well understood. We retrieved 13 such tumors from our pathology archives in patients with a median age of 60years, comprising 1.5% of clear cell renal cell carcinomas. Stage was typically pT4 or pT3 (each 38%). Microscopically, all tumors included a component of low-grade clear cell renal cell carcinoma with usual features. Syncytial-type giant tumor cells possessed voluminous cytoplasm, usually granular and eosinophilic, and numerous nuclei similar to those of the mononuclear tumor cells. Transition between areas of mononuclear and multinucleated cells was sometimes abrupt. Other findings included necrosis (77%), hyaline globules (46%), emperipolesis (46%), and intranuclear cytoplasmic invaginations (23%). Immunohistochemical staining typically revealed both mononuclear and multinucleated cells to be positive for carbonic anhydrase IX, CD10, epithelial membrane antigen, vimentin, and cytokeratin AE1/AE3 and negative for ? human chorionic gonadotropin, TFE3, cathepsin K, cytokeratin 7, cytokeratin 20, HMB45, CD68, smooth muscle actin, and S100. Most patients with available information (7/9) were alive with metastatic disease at the most recent follow-up. Syncytial-type giant cells are an uncommon finding associated with aggressive clear cell renal cell carcinomas. Despite the unusual appearance of this tumor component, its immunoprofile supports an epithelial lineage and argues against trophoblastic, osteoclast-like, or histiocytic differentiation. Reactivity for typical clear cell renal cell carcinoma antigens facilitates discrimination from giant cells of epithelioid angiomyolipoma or other tumors, particularly in a biopsy specimen or a metastatic tumor.
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Molecular pathology of malignant melanoma: changing the clinical practice paradigm toward a personalized approach.
Hum. Pathol.
PUBLISHED: 02-03-2014
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Melanocytic proliferations are notoriously difficult lesions to evaluate histologically, even among experts, as there is a lack of objective, highly reproducible criteria, which can be broadly applied to the wide range of melanocytic lesions encountered in daily practice. These difficult diagnoses are undeniably further compounded by the substantial medicolegal risks of an "erroneous" diagnosis. Molecular information and classification of melanocytic lesions is already vast and constantly expanding. The application of molecular techniques for the diagnosis of benignity or malignancy is, at times, confusing and limits its utility if not used properly. In addition, current and future therapies will necessitate molecular classification of melanoma into one of several distinct subtypes for appropriate patient-specific therapy. An understanding of what different molecular markers can and cannot predict is of the utmost importance. We discuss both mutational analysis and chromosomal gains/losses to help clarify this continually developing and confusing facet of pathology.
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Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma.
Mol. Carcinog.
PUBLISHED: 01-12-2014
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Small cell carcinoma of the prostate (PSCC) is a highly aggressive malignancy that often develops in patients previously treated with hormonal therapy for metastatic prostatic acinar adenocarcinoma. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer and shared by PSCC; however, the role of androgen receptor (AR) gene alterations and interaction with TMPRSS2-ERG rearrangement are incompletely understood in PSCC. Sixty-one cases of PSCC were examined for AR gene copy number and TMPRSS2-ERG rearrangement by fluorescence in situ hybridization (FISH) and AR protein expression by immunohistochemistry. Of 61 cases of PSCC, 51% (31/61) demonstrated increased AR gene copy number (FISH+), 54% (33/61) were positive for TMPRSS2-ERG gene fusion, and 38% (23/61) showed AR protein expression. Of the 31 AR FISH+ cases, 23 also showed TMPRSS2-ERG gene fusion, and 16 expressed AR protein. Of the 33 cases with TMPRSS2-ERG fusion, 28 were AR FISH+ or expressed AR protein. Statistically significant correlations were observed between AR gene copy number or AR protein expression and TMPRSS2-ERG gene fusion (P?=?0.001 and P?=?0.03, respectively). In summary, high AR gene copy number emerges during the development of PSCC, often in association with TMPRSS2-ERG rearrangement. This potential mechanism warrants further study. Improvement will come from understanding the biology of the disease and integrating new therapies into the treatment of this rare and aggressive tumor. © 2014 Wiley Periodicals, Inc.
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Multifunctional theranostic red blood cells for magnetic-field-enhanced in vivo combination therapy of cancer.
Adv. Mater. Weinheim
PUBLISHED: 01-11-2014
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Red blood cells are attached to iron oxide nanoparticles pre-coated with chlorine e6, a photosensitizer, and then loaded with a chemotherapeutic drug, doxorubicin, to enable imaging-guided combined photodynamic and chemotherapy of cancer, achieving excellent synergistic therapeutic effects in an animal tumor model. This work highlights the great promise of integrating cell-based drug-delivery systems with nanotechnology as a biocompatible multifunctional platform for applications in cancer theranostics.
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Hyper-IL-15 suppresses metastatic and autochthonous liver cancer by promoting tumour-specific CD8(+) T cell responses.
J. Hepatol.
PUBLISHED: 01-09-2014
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Liver cancer has a very dismal prognosis due to lack of effective therapy. Here, we studied the therapeutic effects of hyper-interleukin15 (hyper-IL-15), which is composed of IL-15 and the sushi domain of the IL-15 receptor ? chain, on metastatic and autochthonous liver cancers.
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SemFunSim: a new method for measuring disease similarity by integrating semantic and gene functional association.
PLoS ONE
PUBLISHED: 01-01-2014
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Measuring similarity between diseases plays an important role in disease-related molecular function research. Functional associations between disease-related genes and semantic associations between diseases are often used to identify pairs of similar diseases from different perspectives. Currently, it is still a challenge to exploit both of them to calculate disease similarity. Therefore, a new method (SemFunSim) that integrates semantic and functional association is proposed to address the issue.
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Urothelial dysplasia of the bladder: diagnostic features and clinical significance.
Anal. Quant. Cytol. Histol.
PUBLISHED: 12-19-2013
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The 2004 World Health Organization classification system for urothelial neoplasia identifies urothelial dysplasia (low-grade intraurothelial neoplasia) as a premalignant lesion of the urothelium. Although diagnostic criteria of urothelial dysplasia have been improved in recent years, there is a frequent lack of interobserver reproducibility. Follow-up studies suggest that dysplasia is a marker for urothelial instability and disease progression in up to 19% of patients, thus supporting an active clinical follow-up in these patients. The main differential diagnosis of urothelial dysplasia includes flat urothelial lesions with atypia, mainly flat (simple) urothelial hyperplasia, reactive urothelial atypia, urothelial atypia of unknown significance, and urothelial carcinoma in situ (high-grade intraurothelial neoplasia). In most cases, morphologic features alone suffice for diagnosis. Some cases may require a panel of immunohistochemical antibodies consisting of cytokeratin 20, p53 and CD44 for diagnosis. We present pathologic features and clinical significance of urothelial dysplasia with emphasis on differential diagnosis from common flat urothelial lesions with atypia.
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Expression of NFkappaB, ICAM1, and VCAM1 in rheumatic heart disease with atrial fibrillation.
Anal. Quant. Cytol. Histol.
PUBLISHED: 11-29-2013
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To examine the expression of nuclear factor kappaB (NFkappaB), intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1) levels in rheumatic heart disease patients who suffer from atrial fibrillation and those who do not.
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Synthesis of Au-Fe3O4 heterostructured nanoparticles for in vivo computed tomography and magnetic resonance dual model imaging.
Nanoscale
PUBLISHED: 11-18-2013
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Water-soluble Au-Fe3O4 heterostructured nanoparticles with high biocompatibility were synthesized and applied as a dual modality contrast agent. These nanoparticles present strong CT/MRI contrast enhancement in a rabbit model. Low concentrations of Au-Fe3O4 were found to obtain a similar effect to high concentrations of a commercial iodine agent in the CT image.
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Magnetic PEGylated Pt3Co nanoparticles as a novel MR contrast agent: in vivo MR imaging and long-term toxicity study.
Nanoscale
PUBLISHED: 10-30-2013
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Magnetic resonance (MR) imaging using magnetic nanoparticles as the contrast agent has been extensively explored in biomedical imaging and disease diagnosis. Herein, we develop biocompatible polymer coated ultra-small Pt3Co magnetic nanoparticles as a new T2-weighted MR imaging contrast agent. A unique class of alloy Pt3Co nanoparticles is synthesized through a thermal decomposition method. After being modified with polyethylene glycol (PEG), the obtained Pt3Co-PEG nanoparticles exhibit an extremely high T2-weighted relaxivity rate (r2) up to 451.2 mM s(-1), which is much higher than that of Resovist®, a commercial T2-MR contrast agent used in the clinic. In vitro experiments indicate no obvious cytotoxicity of Pt3Co-PEG nanoparticles to various cell lines. After intravenous injection of Pt3Co-PEG nanoparticles, in vivo T2-weighted MR imaging of tumor-bearing mice reveals strong tumor contrast, which is much higher than that offered by injecting Resovist®. We further study the long-term biodistribution and toxicology of this new type of MR contrast nanoparticles after intravenous injection into healthy mice. Despite the significant retention of Pt3Co-PEG nanoparticles in the mouse liver and spleen, no appreciable toxicity of these nanoparticles to the treated animals has been noted in our detailed histological and hematological analysis over a course of 60 days. Our work demonstrates that functionalized Pt3Co nanoparticles may be a promising new type of T2-weighted MR contrast agent potentially useful in biomedical imaging and diagnosis.
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Lymph node-positive bladder cancer: surgical, pathologic, molecular and prognostic aspects.
Expert Rev Anticancer Ther
PUBLISHED: 10-18-2013
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The presence of lymphatic metastasis is associated with markedly worse prognosis in patients with bladder cancer, although surgical resection and chemotherapy can still provide long-term survival for selected patients. The prognostic stratification of patients with positive lymph nodes has been broadly discussed in the current literature and a more extensive pelvic lymph node dissection and thorough pathologic assessment has been advocated. It is clear that stratification using the tumor node metastasis staging system is insufficient to adequately discriminate prognosis between patients with different lymph node involvement. Lymph node density and extranodal extension have been extensively investigated and appear to influence the prognosis of these patients. Molecular markers have been developed to improve the diagnosis of micrometastatic disease, and new targeted therapies have shown promising preclinical results and are now being tested in different clinical scenarios.
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Multilayer dual-polymer-coated upconversion nanoparticles for multimodal imaging and serum-enhanced gene delivery.
ACS Appl Mater Interfaces
PUBLISHED: 10-10-2013
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Upconversion nanoparticles (UCNPs) have been widely explored for various bioapplications because of their unique optical properties, easy surface functionalization, and low cytotoxicity. Herein, we synthesize gadolinium (Gd3+)-doped UCNPs, which are modified first with poly(ethylene glycol) (PEG) and then with two layers of poly(ethylenimine) (PEI) via covalent conjugation and layer-by-layer assembly, respectively. Compared with UCNP-PEG@1×PEI with only one layer of PEI coating, the final complex, UCNP-PEG@2×PEI, with two PEI layers exhibits reduced cytotoxicity and enhanced gene transfection efficiency. It is interesting to find that while free PEI polymer is only effective in gene transfection in a serum-free medium and shows drastically reduced transfection ability if serum is added, UCNP-PEG@2×PEI is able to transfect cells in both serum-free and -containing media and, surprisingly, offers even higher gene transfection efficiency if serum is added. This is likely due to the formation of protein corona on the nanoparticle surface, which triggers the receptor-mediated endocytosis of our UCNP vectors. Considering the upconversion luminescence and magnetic resonance imaging contrasting ability of UCNPs, our novel nanovector could serve as a "trackable" gene-delivery carrier promising for theranostic applications.
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Facile fabrication of biocompatible and tunable multifunctional nanomaterials via iron-mediated atom transfer radical polymerization with activators generated by electron transfer.
ACS Appl Mater Interfaces
PUBLISHED: 09-30-2013
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A novel strategy of preparing multifunctional nanoparticles (NPs) with near infra red (NIR) fluorescence and magnetism showing good hydrophilicity and low toxicity was developed via surface-initiated atom transfer radical polymerization with activators generated by electron transfer (AGET ATRP) of poly(ethylene glycol) monomethyl ether methacrylate (PEGMA) and glycidyl methacrylate (GMA) employing biocompatible iron as the catalyst on the surface of silica coated iron oxide (Fe3O4@SiO2) NPs. The small molecules (CS2), a NIR fluorescent chromophore, can be fixed into the covalently grafted polymer shell of the NPs by chemical reaction through a covalent bond to obtain stable CS2 dotted NPs Fe3O4@SiO2@PPEGMA-co-PGMA@CS2. The fluorescence intensity of the as-prepared NPs could be conveniently regulated by altering the silica shell thickness (varying the feed of silica source TEOS), CS2 feed, or the feed ratio of VPEGMA/VGMA, which are easily realized in the preparation process. Thorough investigation of the properties of the final NPs including in vivo dual modal imaging indicate that such NPs are one of the competitive candidates as imaging agents proving a promising potential in the biomedical area.
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Renal tumors: diagnostic and prognostic biomarkers.
Am. J. Surg. Pathol.
PUBLISHED: 09-13-2013
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The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.
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PEGylated WS2 Nanosheets as a Multifunctional Theranostic Agent for in vivo Dual-Modal CT/Photoacoustic Imaging Guided Photothermal Therapy.
Adv. Mater. Weinheim
PUBLISHED: 09-06-2013
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A new generation of photothermal theranostic agent is developed based on PEGylated WS2 nanosheets. Bimodal in vivo CT/photoacoustic imaging reveals strong tumor contrast after either intratumoral or intravenous injection of WS2 -PEG. In vivo photothermal treatment is then conducted in a mouse tumor model, achieving excellent therapeutic efficacy with complete ablation of tumors. This work promises further explorations of transition-metal dichalcogenides for biomedical applications, such as cancer imaging and therapy.
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Utilization of cell-transferred cytologic smears in detection of EGFR and KRAS mutation on adenocarcinoma of lung.
Mod. Pathol.
PUBLISHED: 08-29-2013
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Cell-transfer technique has been proven useful for performing immunocytochemistry on fine-needle aspiration smears. However, its utility for EGFR and KRAS molecular testing has not been validated. Molecular testing was performed using the cell-transfer technique on both Papanicolaou-stained ethanol-fixed and Hema 3-stained air-dried smears from 32 fine-needle aspiration samples that had diagnoses of adenocarcinoma of the lung, and then was compared to the results of the corresponding formalin-fixed paraffin-embedded tissues. The molecular testing was successfully performed on 32 of 32 ethanol-fixed and 31 of 32 air-dried samples. The molecular results on ethanol-fixed and air-dried smears showed 100% agreement. There is 100% (32/32) agreement for the EGFR and 97% (31/32) agreement for the KRAS between the cell-transfer technique and formalin-fixed paraffin-embedded tissues. One discrepant case was due to low percentage of tumor cells on the smears. Cell-transfer technique is a reliable alternative method for EGFR and KRAS testing if the cell blocks lack adequate cellularity.Modern Pathology advance online publication, 13 December 2013; doi:10.1038/modpathol.2013.220.
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Effects of a selective cyclooxygenase-2 inhibitor (celecoxib) on fracture healing in rats.
Indian J Orthop
PUBLISHED: 08-21-2013
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Several studies suggested that celecoxib interferes with bone healing while others contradict these findings. This study was conducted to investigate the effects of celecoxib on bone healing in rats femur mold with a dose based on body surface area conversion.
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Atypical adenomatous hyperplasia of prostate lacks TMPRSS2-ERG gene fusion.
Am. J. Surg. Pathol.
PUBLISHED: 07-27-2013
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Atypical adenomatous hyperplasia (AAH) is a distinct entity in prostate pathology, defined as a well-circumscribed lobule of closely packed crowded small glands or acini. Although it has been proposed as a precursor lesion to prostate cancer, the biological nature of AAH is currently uncertain. The TMPRSS2-ERG fusion gene is a common recurrent chromosomal rearrangement in prostate cancer and in its precursor lesion, prostatic intraepithelial neoplasia. The prevalence of TMPRSS2-ERG alteration in AAH is unknown. Fifty-five separate prostate specimens containing AAH were investigated by fluorescence in situ hybridization and immunohistochemistry for TMPRSS2-ERG rearrangement. TMPRSS2-ERG rearrangements were not identified in AAH either by fluorescence in situ hybridization or by immunohistochemistry.
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Selective enrichment and production of highly urease active bacteria by non-sterile (open) chemostat culture.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 07-08-2013
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In general, bioprocesses can be subdivided into naturally occurring processes, not requiring sterility (e.g., beer brewing, wine making, lactic acid fermentation, or biogas digestion) and other processes (e.g., the production of enzymes and antibiotics) that typically require a high level of sterility to avoid contaminant microbes overgrowing the production strain. The current paper describes the sustainable, non-sterile production of an industrial enzyme using activated sludge as inoculum. By using selective conditions (high pH, high ammonia concentration, and presence of urea) for the target bacterium, highly active ureolytic bacteria, physiologically resembling Sporosarcina pasteurii were reproducibly enriched and then continuously produced via chemostat operation of the bioreactor. When using a pH of 10 and about 0.2 M urea in a yeast extract-based medium, ureolytic bacteria developed under aerobic chemostat operation at hydraulic retention times of about 10 h with urease levels of about 60 ?mol min?¹ ml?¹ culture. For cost minimization at an industrial scale the costly protein-rich yeast extract medium could be replaced by commercial milk powder or by lysed activated sludge. Glutamate, molasses, or glucose-based media did not result in the enrichment of ureolytic bacteria by the chemostat. The concentration of intracellular urease was sufficiently high such that the produced raw effluent from the reactor could be used directly for biocementation in the field.
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Cytoplasmic OCT4 staining is a sensitive marker of neuroendocrine differentiation.
Hum. Pathol.
PUBLISHED: 07-02-2013
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Previous studies by the authors have described a novel cytoplasmic staining pattern with OCT4 in normal adrenal medullary tissue and in paragangliomas. We aimed to determine if this type of staining is found in other neuroendocrine tissues by examining a broad range of neuroendocrine tumors. Fifty neuroendocrine tumors of various grades and primary organ sites were selected. All cases were immunostained with OCT4 and Ki-67. OCT4 reactivity was then scored for intensity (0-3+) and extent (0-3+). Ki-67 proliferation index was scored as a percentage of total tumor cells. Immunoelectron microscopy was performed to determine precise location of antibody binding within cells. Immunoreactivity was seen in 26 (96%) of 27 cases of carcinoid tumors. The same type of strong staining was seen in 4 (67%) of 6 moderately differentiated neuroendocrine tumors. Only 2 (12%) of 17 poorly differentiated neuroendocrine tumors showed similar staining. A strong, inverse correlation was seen with OCT4 and Ki-67 index. Immunoelectron microscopy showed binding of OCT4 antibody to neurosecretory granules. Cytoplasmic staining of OCT4 is a sensitive marker of neuroendocrine differentiation that has yet to be described in any other tissue or tumor type. These findings show that this antibody has a high affinity for well- to moderately differentiated neuroendocrine tumors. Although comparative studies with other markers and a more extensive analysis of other tissue types are necessary, cytoplasmic staining of OCT4 may prove to be a useful immunostain in the diagnosis of neuroendocrine tumors.
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A pH-sensitive gene delivery system based on folic acid-PEG-chitosan - PAMAM-plasmid DNA complexes for cancer cell targeting.
Biomaterials
PUBLISHED: 06-14-2013
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In this study, pH-sensitive biomaterials coated polymer/DNA nanocomplexes containing a high mobility group box 1 (HMGB1) were developed as an efficient non-viral gene delivery system. HMGB1 is a family of endogenous molecules that contains nuclear locating sequences (NSL). Polyethylene glycol tethered carboxylated chitosan modified with folic acid (FA-PEG-CCTS) was synthesized and its buffering capacity was determined by acid-base titration. A pH-sensitive core-shell system FA-PEG-CCTS/PAMAM/HMGB1/pDNA nanocomplexes (FPCPHDs), was prepared and characterized. Electrophoresis showed that FPCPHDs were resistant to heparin replacement and DNase I digestion. FPCPHDs exhibited only minor toxic effects on HepG2 and KB cells. The results of both luciferase activity assay and RFP fluorescence intensity analysis showed that FPCPHDs enhanced gene transfection and expression in KB cells. Moreover, gene transfection and expression in KB cells were inhibited by free folic acid. Intracellular trafficking of FPCPHDs in KB cells showed that FPCPHDs could rapidly escape from endo-lysosomes and become exclusively located in the nucleus at 3 h post transfection. In addition, FPCPHDs exhibited increased red fluorescence protein (RFP) expression at the tumor site of S180 xenograft nude mice. All results suggest that FPCPHDs is an efficient approach to improve the transfection and expression efficiency in most FR-positive cancer cells.
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Distally based saphenous neurocutaneous perforator flap combined with vac therapy for soft tissue reconstruction and hardware salvage in the lower extremities.
Microsurgery
PUBLISHED: 06-14-2013
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The complex wound with the exposed hardware and infection is one of the common complications after the internal fixation of the tibia fracture. The salvage of hardware and reconstruction of soft tissue defect remain challenging. In this report, we presented our experience on the use of the distally based saphenous neurocutaneous perforator flap combined with vacuum-assisted closure (VAC) therapy for the coverage of the soft tissue defect and the exposed hardware in the lower extremity with fracture. Between January 2008 and July 2010, seven patients underwent the VAC therapy followed by transferring a reversed saphenous neurocutaneous perforator flap for reconstruction of the wound with exposed hardware around the distal tibia. The sizes of the flaps ranged from 6 × 3 cm to 15 × 6 cm. Six flaps survived completely. Partial necrosis occurred in one patient. There were no other complications of repair and donor sites. Bone healing was achieved in all patients. In conclusion, the reversed saphenous neurocutaneous perfortor flaps combined with the VAC therapy might be one of the options to cover the complex wound with exposed hardware in the lower extremities. © 2013 Wiley Periodicals, Inc. Microsurgery, 2013.
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qPCR increases sensitivity to detect cytomegalovirus in formalin-fixed, paraffin-embedded tissue of gastrointestinal biopsies.
Hum. Pathol.
PUBLISHED: 06-07-2013
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Histopathologic diagnosis of gastrointestinal (GI) tract cytomegaloviral (CMV) infection relies on hematoxylin and eosin (H&E)-stained tissue, along with the aid of immunohistochemistry (IHC). However, non-classic appearing inclusions or atypical IHC staining patterns remain an ongoing concern for pathologists. We reported the use of real-time polymerase chain reaction (qPCR) on nucleic acid extracted from paraffin-embedded, formalin-fixed tissue of GI biopsies from cases of CMV infection (n = 91) diagnosed by H&E and IHC. Seventy-nine biopsies, including normal colon biopsies (n = 35), active colitis (n = 25), and active duodenitis (n = 19), were used as negative controls. Of 91 CMV-positive biopsies diagnosed by histology, 88 tested positive by qPCR, with a sensitivity of 96.7%. Of 79 negative controls, 78 were negative and 1 positive by qPCR, resulting in a specificity of 98.7%. Of the cases that were positive for CMV by histopathology, there were an additional 40 biopsies taken from these patients either during the same or previous procedures, some taken just days prior, which were negative for CMV by histology. Interestingly, 22 (55%) of these biopsies tested positive by qPCR, which correlated well with additional clinical CMV results. By defining qPCR as the "gold standard" for a CMV result, histology (H&E and/or IHC) had a sensitivity and specificity of 79% and 97%, respectively. Eighteen biopsies were found negative by H&E and equivocal by IHC. Among them, 14 (78%) tested positive for CMV by qPCR, which also correlated well with additional clinical results. qPCR is a sensitive, specific, and rapid molecular tool that may be helpful to aid in early diagnosis of CMV infection on equivocal or clinically highly suspicious small GI biopsies.
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HOXB13 is a sensitive and specific marker of prostate cells, useful in distinguishing between carcinomas of prostatic and urothelial origin.
Virchows Arch.
PUBLISHED: 06-05-2013
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The origin of a primary or metastatic carcinoma in the pelvic area is sometimes difficult to establish, in particular the distinction between those originating in the bladder and the prostate. A candidate marker is the HOXB13 gene, essential for prostate development. Some studies have shown expression of HOXB13 protein by immunohistochemistry in the nuclear compartment of benign prostate luminal epithelium and prostate carcinoma. Forty-two cases of biopsies and resection specimens of the prostate and urinary bladder, metastatic lymph nodes, and pelvic masses were retrieved from our databases. In all cases, doubt persisted regarding prostatic versus urothelial origin. All cases were stained for CK7, p63, p504s, PSA, CK20, and HOXB13. Chromogranin A, CD56, and synaptophysin were used when neuroendocrine differentiation was suspected. HOXB13 staining was negative or only weakly positive in all carcinomas of urothelial origin. Three of four carcinomas with neuroendocrine differentiation did not express HOXB13. The fourth carcinoma, in a patient with a history of prostate carcinoma, was positive. In two cases with a synchronous prostatic and urothelial carcinoma, HOXB13 was exclusively expressed in the prostatic carcinoma. Our results demonstrate that HOXB13 expression identifies prostatic origin of a carcinoma with good sensitivity (89 %) and very good specificity (100 %). HOXB13 is a specific and sensitive marker for prostate cells and a valuable diagnostic tool, especially when poorly differentiated or neuroendocrine tumors are encountered. These results justify testing of HOXB13 as a prostate-specific carcinoma marker in larger cohorts for a more thorough evaluation of its sensitivity and specificity.
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PEG-functionalized iron oxide nanoclusters loaded with chlorin e6 for targeted, NIR light induced, photodynamic therapy.
Biomaterials
PUBLISHED: 06-01-2013
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Magnetic targeting that utilizes a magnetic field to specifically delivery theranostic agents to targeted tumor regions can greatly improve the cancer treatment efficiency. Herein, we load chlorin e6 (Ce6), a widely used PS molecule in PDT, on polyethylene glycol (PEG) functionalized iron oxide nanoclusters (IONCs), obtaining IONC-PEG-Ce6 as a theranostic agent for dual-mode imaging guided and magnetic-targeting enhanced in vivo PDT. Interestingly, after being loaded on PEGylated IONCs, the absorbance/excitation peak of Ce6 shows an obvious red-shift from ~650 nm to ~700 nm, which locates in the NIR region with improved tissue penetration. Without noticeable dark toxicity, Ce6 loaded IONC-PEG (IONC-PEG-Ce6) exhibits significantly accelerated cellular uptake compared with free Ce6, and thus offers greatly improved in vitro photodynamic cancer cell killing efficiency under a low-power light exposure. After demonstrating the magnetic field (MF) enhanced PDT using IONC-PEG-Ce6, we then further test this concept in animal experiments. Owing to the strong magnetism of IONCs and the long blood-circulation time offered by the condensed PEG coating, IONC-PEG-Ce6 shows strong MF-induced tumor homing ability, as evidenced by in vivo dual modal optical and magnetic resonance (MR) imaging. In vivo PDT experiment based magnetic tumor targeting using IONC-PEG-Ce6 is finally carried out, achieving high therapeutic efficacy with dramatically delayed tumor growth after just a single injection and the MF-enhanced photodynamic treatment. Considering the biodegradability and non-toxicity of iron oxide, our IONC-PEG-Ce6 presented in this work may be a useful multifunctional agent promising in photodynamic cancer treatment under magnetic targeting.
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Biomarkers in bladder cancer: Translational and clinical implications.
Crit. Rev. Oncol. Hematol.
PUBLISHED: 05-24-2013
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Bladder cancer is associated with high recurrence and mortality rates. These tumors show vast heterogeneity reflected by diverse morphologic manifestations and various molecular alterations associated with these disease phenotypes. Biomarkers that prospectively evaluate disease aggressiveness, progression risk, probability of recurrence and overall prognosis would improve patient care. Integration of molecular markers with conventional pathologic staging of bladder cancers may refine clinical decision making for the selection of adjuvant and salvage therapy. In the past decade, numerous bladder cancer biomarkers have been identified, including various tumor suppressor genes, oncogenes, growth factors, growth factor receptors, hormone receptors, proliferation and apoptosis markers, cell adhesion molecules, stromal factors, and oncoproteins. Recognition of two distinct pathways for urothelial carcinogenesis represents a major advance in the understanding and management of this disease. Nomograms for combining results from multiple biomarkers have been proposed to increase the accuracy of clinical predictions. The scope of this review is to summarize the major biomarker findings that may have translational and clinical implications.
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Cystic partially regressed clear cell renal cell carcinoma: a potential mimic of multilocular cystic renal cell carcinoma.
Histopathology
PUBLISHED: 04-29-2013
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To study clear cell renal cell carcinomas with predominant cystic and sclerotic components, in which a solid epithelial component precluded a diagnosis of multilocular cystic renal cell carcinoma. We designated these tumours cystic partially regressed clear cell renal cell carcinoma.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.