Validation of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinomas.

PubMed

Mosquera, Juan-Miguel; Dal Cin, Paola; Mertz, Kirsten D; Perner, Sven; Davis, Ian J; Fisher, David E; Rubin, Mark A; Hirsch, Michelle S

2011-09-01

Renal cell carcinomas (RCCs) with an Xp11.2 translocation predominantly affect young patients, and can present at an advanced stage. However, more cases in older patients and incidentally detected cancers at earlier stages are also being identified. As the histology of Xp11.2 RCCs overlaps with clear cell and papillary RCCs, it is not infrequent that Xp11.2 RCCs are overlooked and misdiagnosed. The objective of this study was to validate the use of fluorescence in-situ hybridization (FISH) for identifying Xp11.2 RCCs. One hundred fifty-eight consecutive, unselected renal tumors were evaluated in tissue microarrays, including 109 clear cell RCCs, 20 papillary RCCs, 3 RCCs with mixed papillary and clear cell features, 1 Xp11.2 translocation RCC, 8 chromophobe RCCs, 10 oncocytomas, and 7 angiomyolipomas. FISH evaluation was performed blinded to karyotype data, available in about two-thirds of cases. Furthermore, conventional sections of 4 Xp11.2 RCCs, 4 RCCs with mixed papillary and clear cell features, and 4 cases of alveolar soft part sarcoma (the latter for control purposes) were also assessed by FISH. Break-apart signals were homogeneously identified throughout tumor cells in 2 cases from the tissue microarrays including 1 known Xp11.2 RCC and 1 misdiagnosed Xp11.2 RCC. All conventional sections from the Xp11.2 RCC and alveolar soft part sarcoma cases were positive for the TFE3 rearrangement by FISH. All remaining cases were negative. Our study shows the clinical application of FISH in formalin-fixed, paraffin-embedded tissue for detection of Xp11.2 translocation RCCs and other tumors with this genetic aberration.

Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

PubMed

Arpaci, Rabia Bozdoğan; Kara, Tuba; Porgali, Canan; Serinsoz, Ebru; Polat, Ayse; Vayisoglu, Yusuf; Ozcan, Cengiz

2014-05-01

Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

Enhancement of photocurrent in epitaxial lift-off thin-film GaInNAsSb solar cells due to light-confinement structure

NASA Astrophysics Data System (ADS)

Miyashita, Naoya; Behaghel, Benoît; Guillemoles, Jean-François; Okada, Yoshitaka

2018-07-01

This work focuses on the characterization of GaInNAsSb solar cells whose substrates are removed via the epitaxial lift-off (ELO) technique. As a result of the substrate removal, increases in the photocurrent and the interference feature were clearly observed. This is clear evidence of the light-confinement effect, whereby some of the unabsorbed photons at the rear metal contact were reflected back towards the front side of the ELO thin-film cell. We successfully demonstrated that the ELO technique can be applied for the GaInNAsSb cell, and the light management should add flexibility in designing the cell structures.

Prevalence of endometriosis in epithelial ovarian cancer. Analysis of the associated clinical features and study on molecular mechanisms involved in the possible causality.

PubMed

Machado-Linde, F; Sánchez-Ferrer, M L; Cascales, P; Torroba, A; Orozco, R; Silva Sánchez, Y; Nieto, A; Fiol, G

2015-01-01

To determine the prevalence of endometriosis in patients with epithelial ovarian cancer and explore the differences between women with endometrioid and clear-cell histologic subtypes with and without associated endometriosis. The medical charts of 496 patients with epithelial ovarian cancer at the Hospital Virgin de la Arrixaca (Murcia, Spain) between 1971 and 2010 were reviewed. Endometriosis was present in 27 (5.4%) of the 496 cases (p < 0001), and was associated with the endometrioid histotype in 13/45 cases (29%) and with the clear cell histotype in 7/22 (32%). The prevalence of an association with endometriosis according to histologic type was 28.8% (13/45) for endometrioid carcinoma and 31.8% (7/22) for clear-cell carcinoma. Both endometrioid and clear-cell ovarians tumours are associated with pelvic endometriosis. Patients with endometiosis associated ovarian cancer differ from non-endometiosis associated ovarian cancer in their clinical characteristics.

Single-cell genetic analysis validates cytopathological identification of circulating cancer cells in patients with clear cell renal cell carcinoma.

PubMed

Broncy, Lucile; Njima, Basma Ben; Méjean, Arnaud; Béroud, Christophe; Romdhane, Khaled Ben; Ilie, Marius; Hofman, Veronique; Muret, Jane; Hofman, Paul; Bouhamed, Habiba Chaabouni; Paterlini-Bréchot, And Patrizia

2018-04-13

Circulating Rare Cells (CRC) are non-haematological cells circulating in blood. They include Circulating Cancer Cells (CCC) and cells with uncertain malignant features (CRC-UMF) according to cytomorphology. Clear cell renal cell carcinomas frequently bear a mutated Von Hippel-Lindau (VHL) gene. To match blind genetic analysis of CRC and tumor samples with CRC cytopathological diagnosis. 29/30 patients harboured CRC (20 harboured CCC, 29 CRC-UMF) and 25/29 patients carried VHL mutations in their tumour. 205 single CRC (64 CCC, 141 CRC-UMF) provided genetic data. 57/57 CCC and 104/125 CRC-UMF from the 25 patients with VHL-mutated tumor carried the same VHL mutation detected in the tumor. Seven CCC and 16 CRC-UMF did not carry VHL mutations but were found in patients with wild-type VHL tumor tissue. All the CCC and 83,2% (104/125) of the CRC-UMF were found to carry the same VHL mutation identified in the corresponding tumorous tissue, validating cytopathological identification of CCC in patients with clear cell renal cell carcinoma. The blood of 30 patients with clear cell renal cell carcinoma was treated by ISET ® for CRC isolation, cytopathology and single-cell VHL mutations analysis, performed blindly and compared to VHL mutations of corresponding tumor tissues and leukocytes.

Renal cell carcinoma with rhabdoid-like features lack intracytoplasmic inclusion bodies and show aggressive behavior.

PubMed

Sugimoto, Masaaki; Kohashi, Kenichi; Kuroiwa, Kentaro; Abe, Tatsuro; Yamada, Yuichi; Shiota, Masaki; Imada, Kenjiro; Naito, Seiji; Oda, Yoshinao

2016-03-01

In renal cell carcinoma (RCC), tumor cells with rhabdoid features are characterized by eccentric nuclei, prominent nucleoli, and eosinophilic cytoplasm with intracytoplasmic inclusion bodies. In RCC, tumor cells have also been observed resembling rhabdomyoblasts or rhabdoid but without intracytoplasmic inclusion bodies, and here, we defined these rhabdoid-like features of these cells. To this end, we studied a series of clear cell RCC (ccRCC) with rhabdoid features and compared them with a series of ccRCC with rhabdoid-like features to clarify the differences in the immunohistochemical profile and biological behavior. From 695 cases of ccRCC (80.8 % of all RCCs), 18 cases with rhabdoid features (2.1 % of all RCCs) and 25 cases with rhabdoid-like features (2.9 % of all RCCs) were investigated. The 5-year survival rate for ccRCC with rhabdoid features was 44.7 % and for ccRCC with rhabdoid-like features 30.3 %. Although ccRCC with rhabdoid features showed immunohistochemical co-expression of epithelial markers and vimentin as seen in malignant rhabdoid tumors, ccRCC with rhabdoid-like features showed no such co-expression. Multivariate analyses of cancer-specific survival revealed that perinephric tissues invasion was an independent prognostic factor in ccRCC with rhabdoid features (p = 0.0253) but not in ccRCC with rhabdoid-like features. In summary, although their prognosis is similar, the marker profile and pattern of extension of ccRCC with rhabdoid-like is different from that of ccRCC with rhabdoid features. Therefore, ccRCC with rhabdoid-like features should be distinguished from ccRCC with rhabdoid features.

Clear cell trichoblastoma: a clinicopathological and ultrastructural study of two cases.

PubMed

Kazakov, Dmitry V; Mentzel, Thomas; Erlandson, Robert A; Mukensnabl, Petr; Michal, Michal

2006-06-01

Clear cell change in basal cell carcinomas is a well-recognized phenomenon, but is obviously rare in trichoblastomas. We present two cases of clear cell trichoblastoma in which clear cell change was very much prominent, and the results of an ultrastructural study intended to explore the basis of that feature. Both our patients were women, aged 56 and 77 years, who presented with solitary, slowly growing nodules that measured 3 to 5 cm in largest dimension and were located on the scalp and the flexor aspect of the lower arm. Microscopically, the tumors in both cases were symmetric, non-ulcerated, and composed of variably sized and shaped (cribriform, racemiform, strands, cords, nodules) aggregations of monomorphous basaloid epithelial cells that were associated with a specific trichogenic stroma. Common to both tumors was clear cell cytoplasm evident in the majority of the epithelial cells in one case and almost in the entire epithelial cell population in the other. In most epithelial aggregations the epithelial cells with clear cytoplasm often appeared columnar and were arranged in a palisade along a recognizable basal membrane, thus indicative of outer sheath differentiation at the bulb. There were other signs of follicular differentiation. Ultrastructurally, variably sized clusters of uniform small basaloid epithelial cells were separated from the stroma by a thin discontinuous basement membrane. In addition to the usual organelles, the cytoplasm contained fairly conspicuous tonofilaments and variably sized vacuoles devoid of a limiting membrane, located between the palisaded nuclei and the outer cell membrane. The majority of vacuoles were empty, although clumps of a finely granular substance were occasionally evident. No distinct lipid droplets or glycogen particles were identified. The basaloid cells were joined by scattered small desmosomes. These findings were consistent with trichilemmal differentiation at the bulb.

The Presence of Vascular Mimicry Predicts High Risk of Clear Cell Renal Cell Carcinoma after Radical Nephrectomy.

PubMed

Zhou, Lin; Chang, Yuan; Xu, Le; Liu, Zheng; Fu, Qiang; Yang, Yuanfeng; Lin, Zongming; Xu, Jiejie

2016-08-01

Vascular mimicry is a type of tumor cell plasticity. The aim of this study was to determine the prognostic value of vascular mimicry in patients with clear cell renal cell carcinoma. We performed a retrospective cohort study in 387 patients with clear cell renal cell carcinoma who underwent radical nephrectomy at Zhongshan Hospital, Fudan University between 2008 and 2009. Pathological features, baseline patient characteristics and followup data were recorded. Vascular mimicry in clear cell renal cell carcinoma tissue was identified by CD31-periodic acid-Schiff double staining. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on recurrence-free survival. The concordance index and the Akaike information criterion were used to assess the predictive accuracy and sufficiency of different models. Positive vascular mimicry staining occurred in 25 of 387 clear cell renal cell carcinoma cases (6.5%) and it was associated with an increased risk of recurrence (log-rank p <0.001). Incorporating vascular mimicry into pT stage, Fuhrman grade and Leibovich score helped refine individual risk stratification. Moreover, vascular mimicry was identified as an independent prognostic factor (p = 0.001). It was entered into a nomogram together with pT stage, Fuhrman grade, tumor size and necrosis. In the primary cohort the Harrell concordance index for the established nomogram to predict recurrence-free survival was slightly higher than that of the Leibovich model (0.850 vs. 0.823), which failed to reach statistical significance (p = 0.158). Vascular mimicry could be a potential prognosticator for recurrence-free survival in patients with clear cell renal cell carcinoma after radical nephrectomy. Further external validation and functional analysis should be pursued to assess its potential prognostic and therapeutic values for clear cell renal cell carcinoma. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Germ cell tumour growth patterns originating from clear cell carcinomas of the ovary and endometrium: a comparative immunohistochemical study favouring their origin from somatic stem cells.

PubMed

Nogales, Francisco F; Prat, Jaime; Schuldt, Maolly; Cruz-Viruel, Nelly; Kaur, Baljeet; D'Angelo, Emanuela; Matias-Guiu, Xavier; Vidal, August; McCluggage, W Glenn; Oosterhuis, J Wolter

2018-03-01

To report a series of 11 ovarian and one endometrial neoplasm in elderly patients with mixed clear cell tumour and germ cell tumour (GCT) components, to compare their immunohistochemical profiles and demonstrate a putative stem cell population. The clear cell tumours included 11 clear cell carcinomas (CCC) and one borderline clear cell tumour, while the GCT always included glandular yolk sac tumour (YST). In four cases, there were also foci of teratoma with immature neuroepithelial and endodermal tissues and undifferentiated areas showing true embryoids. To distinguish between the clear cell and YST components, the following antibodies were used: HNF1-β, napsin-A, cytokeratin 7 (CK7), PAX8, EMA, AFP, SALL4, villin, glypican-3 (GPC-3), GATA3, HepPar-1, OCT4, CDX2, CD30 and SOX2. HNF1-β, CK7, EMA and GPC-3 were often expressed in both components. Other markers had higher specificity for each cellular lineage; napsin-A and PAX8 were expressed only in CCC, while SALL4, villin, AFP and HepPar-1 were positive in the glandular YST component but negative in the clear cell component. OCT4 expression occurred in six of 10 cases and consistently in teratoma (four of four). There is considerable immunophenotypical overlap between the two components in these mixed neoplasms, and a panel of markers should be used to facilitate the distinction. We propose that OCT4-expressing somatic cancer cells differentiate into GCT and represent spontaneously induced pluripotent stem cells, possibly conditioned by age-related epigenetic factors. These neoplasms have features of prepubertal type GCT showing lack of 12p gain, preponderance of YST and coexistence with immature neuroectoderm. However, there may also be undifferentiated stem cell areas with embryoid bodies, of the type seen in postpubertal testicular GCT, but lacking a complete embryonal carcinoma immunophenotype. © 2017 John Wiley & Sons Ltd.

Spectroscopy and atomic force microscopy of biomass.

PubMed

Tetard, L; Passian, A; Farahi, R H; Kalluri, U C; Davison, B H; Thundat, T

2010-05-01

Scanning probe microscopy has emerged as a powerful approach to a broader understanding of the molecular architecture of cell walls, which may shed light on the challenge of efficient cellulosic ethanol production. We have obtained preliminary images of both Populus and switchgrass samples using atomic force microscopy (AFM). The results show distinctive features that are shared by switchgrass and Populus. These features may be attributable to the lignocellulosic cell wall composition, as the collected images exhibit the characteristic macromolecular globule structures attributable to the lignocellulosic systems. Using both AFM and a single case of mode synthesizing atomic force microscopy (MSAFM) to characterize Populus, we obtained images that clearly show the cell wall structure. The results are of importance in providing a better understanding of the characteristic features of both mature cells as well as developing plant cells. In addition, we present spectroscopic investigation of the same samples.

Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

PubMed

Cochrane, Dawn R; Tessier-Cloutier, Basile; Lawrence, Katherine M; Nazeran, Tayyebeh; Karnezis, Anthony N; Salamanca, Clara; Cheng, Angela S; McAlpine, Jessica N; Hoang, Lien N; Gilks, C Blake; Huntsman, David G

2017-09-01

Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Multicentric primary extramammary Paget disease: a Toker cell disorder?

PubMed

Hashemi, Pantea; Kao, Grace F; Konia, Thomas; Kauffman, Lisa C; Tam, Christine C; Sina, Bahram

2014-07-01

Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

Intraductal glycogen-rich clear cell carcinoma of the breast: a rare presentation and review of the literature.

PubMed

Salemis, Nikolaos S

2012-08-01

Glycogen-rich clear cell carcinoma of the breast is a rare histological subtype of breast cancer, accounting for 0.9-2.8% of all breast cancer cases. Fewer than 100 cases have been reported in the literature. Most of these tumors are invasive carcinomas. The intraductal glycogen-rich clear cell carcinoma is a very rare occurrence. Herein is described a case of a pure intraductal glycogen-rich clear cell carcinoma of the breast in a 42-year-old premenopausal woman. A literature review has also been carried out. Mammography was inconclusive due to the presence of dense breast tissue, but magnetic resonance imaging (MRI) showed several nodular lesions measuring 7 × 6 cm in diameter and involving the upper aspect of the right breast suggestive of multifocal malignancy. A modified radical mastectomy was performed. The patient started hormonal therapy with tamoxifen and is currently well 16 months after surgery. A pure intraductal glycogen-rich clear cell carcinoma of the breast is a very rare occurrence. The case presented here exhibited uncommon MRI features, whereas the tumor size is one of the largest reported in the literature. Mammography may be inconclusive in the presence of dense breast tissue, but MRI is of great importance in the preoperative evaluation of the patient.

A Phenotyping Method of Giant Cells from Root-Knot Nematode Feeding Sites by Confocal Microscopy Highlights a Role for CHITINASE-LIKE 1 in Arabidopsis.

PubMed

Cabrera, Javier; Olmo, Rocio; Ruiz-Ferrer, Virginia; Abreu, Isidro; Hermans, Christian; Martinez-Argudo, Isabel; Fenoll, Carmen; Escobar, Carolina

2018-02-01

Most effective nematicides for the control of root-knot nematodes are banned, which demands a better understanding of the plant-nematode interaction. Understanding how gene expression in the nematode-feeding sites relates to morphological features may assist a better characterization of the interaction. However, nematode-induced galls resulting from cell-proliferation and hypertrophy hinders such observation, which would require tissue sectioning or clearing. We demonstrate that a method based on the green auto-fluorescence produced by glutaraldehyde and the tissue-clearing properties of benzyl-alcohol/benzyl-benzoate preserves the structure of the nematode-feeding sites and the plant-nematode interface with unprecedented resolution quality. This allowed us to obtain detailed measurements of the giant cells' area in an Arabidopsis line overexpressing CHITINASE-LIKE-1 ( CTL1 ) from optical sections by confocal microscopy, assigning a role for CTL1 and adding essential data to the scarce information of the role of gene repression in giant cells. Furthermore, subcellular structures and features of the nematodes body and tissues from thick organs formed after different biotic interactions, i.e., galls, syncytia, and nodules, were clearly distinguished without embedding or sectioning in different plant species ( Arabidopsis , cucumber or Medicago ). The combination of this method with molecular studies will be valuable for a better understanding of the plant-biotic interactions.

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

PubMed Central

Uno, K; Homma, S; Satoh, T; Nakanishi, K; Abe, D; Matsumoto, K; Oki, A; Tsunoda, H; Yamaguchi, I; Nagasawa, T; Yoshikawa, H; Aonuma, K

2007-01-01

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE. PMID:17211468

Expanding the histologic spectrum of mucinous tubular and spindle cell carcinoma of the kidney.

PubMed

Fine, Samson W; Argani, Pedram; DeMarzo, Angelo M; Delahunt, Brett; Sebo, Thomas J; Reuter, Victor E; Epstein, Jonathan I

2006-12-01

Mucinous tubular and spindle cell carcinomas (MTSCs) are polymorphic neoplasms characterized by small, elongated tubules lined by cuboidal cells and/or cords of spindled cells separated by pale mucinous stroma. Nonclassic morphologic variants and features of MTSC have not been well studied. We identified 17 previously unreported MTSCs from Surgical Pathology and consultative files of the authors and their respective institutions and studied their morphologic features. A total of 10/17 cases were considered "classic," as described above, with 5/10 showing at least focal (20% to 50%) tubular predominance without apparent mucinous matrix. Alcian blue staining revealed abundant (>50%) mucin in all classic cases. Seven of 17 MTSCs were classified as "mucin-poor," with little to no extracellular mucin appreciable by hematoxylin and eosin. Four of these cases showed equal tubular and spindled morphology, 2 cases showed spindle cell predominance (70%; 95%), and 1 case showed tubular predominance (90%). In 5/7 mucin-poor cases, staining for Alcian blue revealed scant (<10%) mucin in cellular areas with the other 2 cases having 30% mucin. Unusual histologic features identified in the 17 cases were: foamy macrophages (n=8), papillations/well formed papillae (n=6/n=1), focal clear cells in tubules (n=3), necrosis (n=3), oncocytic tubules (n=2; 40%, 5%), numerous small vacuoles (n=2), heterotopic bone (n=1), psammomatous calcification (n=1), and nodular growth with lymphocytic cuffing (n=1). An exceptional case contained a well-circumscribed, HMB45-positive angiomyolipoma within the MTSC. MTSCs may be "mucin-poor" and show a marked predominance of either of its principal morphologic components, which coupled with the presence of other unusual features such as clear cells, papillations, foamy macrophages, and necrosis, may mimic other forms of renal cell carcinoma. Pathologists must be aware of the spectrum of histologic findings within MTSCs to ensure their accurate diagnosis.

Clear cell hidradenocarcinoma--a case report with unusual in situ malignant changes.

PubMed

Al-Irhayim, B

1984-05-01

Clear cell hidradenocarcinoma is a rare tumour, the histogenesis of which has been much debated in the past. However, it is now considered a tumour of sweat gland origin. Presented herewith is a report of a case with unusual histological features of in situ malignant changes within sweat glands. These changes very closely simulate lobular cancerisation of the breast. On reviewing the English literature on the histopathology of sweat gland tumours, we have not found similar histological findings. These histological findings provide supportive evidence of the sweat gland origin of these tumours.

Automatic and adaptive heterogeneous refractive index compensation for light-sheet microscopy.

PubMed

Ryan, Duncan P; Gould, Elizabeth A; Seedorf, Gregory J; Masihzadeh, Omid; Abman, Steven H; Vijayaraghavan, Sukumar; Macklin, Wendy B; Restrepo, Diego; Shepherd, Douglas P

2017-09-20

Optical tissue clearing has revolutionized researchers' ability to perform fluorescent measurements of molecules, cells, and structures within intact tissue. One common complication to all optically cleared tissue is a spatially heterogeneous refractive index, leading to light scattering and first-order defocus. We designed C-DSLM (cleared tissue digital scanned light-sheet microscopy) as a low-cost method intended to automatically generate in-focus images of cleared tissue. We demonstrate the flexibility and power of C-DSLM by quantifying fluorescent features in tissue from multiple animal models using refractive index matched and mismatched microscope objectives. This includes a unique measurement of myelin tracks within intact tissue using an endogenous fluorescent reporter where typical clearing approaches render such structures difficult to image. For all measurements, we provide independent verification using standard serial tissue sectioning and quantification methods. Paired with advancements in volumetric image processing, C-DSLM provides a robust methodology to quantify sub-micron features within large tissue sections.Optical clearing of tissue has enabled optical imaging deeper into tissue due to significantly reduced light scattering. Here, Ryan et al. tackle first-order defocus, an artefact of a non-uniform refractive index, extending light-sheet microscopy to partially cleared samples.

Cell adhesion on nanotextured slippery superhydrophobic substrates.

PubMed

Di Mundo, Rosa; Nardulli, Marina; Milella, Antonella; Favia, Pietro; d'Agostino, Riccardo; Gristina, Roberto

2011-04-19

In this work, the response of Saos2 cells to polymeric surfaces with different roughness/density of nanometric dots produced by a tailored plasma-etching process has been studied. Topographical features have been evaluated by atomic force microscopy, while wetting behavior, in terms of water-surface adhesion energy, has been evaluated by measurements of drop sliding angle. Saos2 cytocompatibility has been investigated by scanning electron microscopy, fluorescent microscopy, and optical microscopy. The similarity in outer chemical composition has allowed isolation of the impact of the topographical features on cellular behavior. The results indicate that Saos2 cells respond differently to surfaces with different nanoscale topographical features, clearly showing a certain inhibition in cell adhesion when the nanoscale is particularly small. This effect appears to be attenuated in surfaces with relatively bigger nanofeatures, though these express a more pronounced slippery/dry wetting character. © 2011 American Chemical Society

L-DOPA decarboxylase mRNA levels provide high diagnostic accuracy and discrimination between clear cell and non-clear cell subtypes in renal cell carcinoma.

PubMed

Papadopoulos, Emmanuel I; Petraki, Constantina; Gregorakis, Alkiviadis; Chra, Eleni; Fragoulis, Emmanuel G; Scorilas, Andreas

2015-06-01

Renal cell carcinoma (RCC) is the most frequent type of kidney cancer. RCC patients frequently present with arterial hypertension due to various causes, including intrarenal dopamine deficiency. L-DOPA decarboxylase (DDC) is the gene encoding the enzyme that catalyzes the biosynthesis of dopamine in humans. Several studies have shown that the expression levels of DDC are significantly deregulated in cancer. Thus, we herein sought to analyze the mRNA levels of DDC and evaluate their clinical significance in RCC. DDC levels were analyzed in 58 surgically resected RCC tumors and 44 adjacent non-cancerous renal tissue specimens via real-time PCR. Relative levels of DDC were estimated by applying the 2(-ΔΔC)T method, while their diagnostic accuracy and correlation with the clinicopathological features of RCC tumors were assessed by comprehensive statistical analysis. DDC mRNA levels were found to be dramatically downregulated (p<0.001) in RCC tumors, exhibiting remarkable diagnostic accuracy as assessed by ROC curve analysis (AUC: 0.910; p<0.001) and logistic regression (OR: 0.678; p=0.001). Likewise, DDC was found to be differentially expressed between clear cell RCC and the group of non-clear cell subtypes (p=0.001) consisted of papillary and chromophobe RCC specimens. Furthermore, a statistically significant inverse correlation was also observed when the mRNA levels of DDC were analyzed in relation to tumor grade (p=0.049). Our data showed that DDC constitutes a highly promising molecular marker for RCC, exhibiting remarkable diagnostic accuracy and potential to discriminate between clear cell and non-clear cell histological subtypes of RCC. Copyright © 2015. Published by Elsevier Inc.

Thyroid Regeneration: Characterization of Clear Cells After Partial Thyroidectomy

PubMed Central

Ozaki, Takashi; Matsubara, Tsutomu; Seo, Daekwan; Okamoto, Minoru; Nagashima, Kunio; Sasaki, Yoshihito; Hayase, Suguru; Murata, Tsubasa; Liao, Xiao-Hui; Hanson, Jeffrey; Rodriguez-Canales, Jaime; Thorgeirsson, Snorri S.; Kakudo, Kennichi; Refetoff, Samuel

2012-01-01

Although having the capacity to grow in response to a stimulus that perturbs the pituitary-thyroid axis, the thyroid gland is considered not a regenerative organ. In this study, partial thyroidectomy (PTx) was used to produce a condition for thyroid regeneration. In the intact thyroid gland, the central areas of both lobes served as the proliferative centers where microfollicles, and bromodeoxyuridine (BrdU)-positive and/or C cells, were localized. Two weeks after PTx, the number of BrdU-positive cells and cells with clear or faintly eosinophilic cytoplasm were markedly increased in the central area and continuous to the cut edge. Clear cells were scant in the cytoplasm, as determined by electron microscopy; some retained the characteristics of calcitonin-producing C cells by having neuroendocrine granules, whereas others retained follicular cell-specific features, such as the juxtaposition to a lumen with microvilli. Some cells were BrdU-positive and expressed Foxa2, the definitive endoderm lineage marker. Serum TSH levels drastically changed due to the thyroidectomy-induced acute reduction in T4-generating tissue, resulting in a goitrogenesis setting. Microarray followed by pathway analysis revealed that the expression of genes involved in embryonic development and cancer was affected by PTx. The results suggest that both C cells and follicular cells may be altered by PTx to become immature cells or immature cells that might be derived from stem/progenitor cells on their way to differentiation into C cells or follicular cells. These immature clear cells may participate in the repair and/or regeneration of the thyroid gland. PMID:22454152

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome.

PubMed

Curriu, Marta; Carrillo, Jorge; Massanella, Marta; Rigau, Josepa; Alegre, José; Puig, Jordi; Garcia-Quintana, Ana M; Castro-Marrero, Jesus; Negredo, Eugènia; Clotet, Bonaventura; Cabrera, Cecilia; Blanco, Julià

2013-03-20

Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability. Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups. CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals. Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS.

Screening NK-, B- and T-cell phenotype and function in patients suffering from Chronic Fatigue Syndrome

PubMed Central

2013-01-01

Background Chronic Fatigue Syndrome (CFS) is a debilitating neuro-immune disorder of unknown etiology diagnosed by an array of clinical manifestations. Although several immunological abnormalities have been described in CFS, their heterogeneity has limited diagnostic applicability. Methods Immunological features of CFS were screened in 22 CFS diagnosed individuals fulfilling Fukuda criteria and 30 control healthy individuals. Peripheral blood T, B and NK cell function and phenotype were analyzed by flow cytometry in both groups. Results CFS diagnosed individuals showed similar absolute numbers of T, B and NK cells, with minor differences in the percentage of CD4+ and CD8+ T cells. B cells showed similar subset frequencies and proliferative responses between groups. Conversely, significant differences were observed in T cell subsets. CFS individuals showed increased levels of T regulatory cells (CD25+/FOXP3+) CD4 T cells, and lower proliferative responses in vitro and in vivo. Moreover, CD8 T cells from the CFS group showed significantly lower activation and frequency of effector memory cells. No clear signs of T-cell immunosenescence were observed. NK cells from CFS individuals displayed higher expression of NKp46 and CD69 but lower expression of CD25 in all NK subsets defined. Overall, T cell and NK cell features clearly clustered CFS individuals. Conclusions Our findings suggest that alterations in T-cell phenotype and proliferative response along with the specific signature of NK cell phenotype may be useful to identify CFS individuals. The striking down modulation of T cell mediated immunity may help to understand intercurrent viral infections in CFS. PMID:23514202

Intraductal Glycogen-Rich Clear Cell Carcinoma of the Breast: A Rare Presentation and Review of the Literature

PubMed Central

Salemis, Nikolaos S.

2012-01-01

Background Glycogen-rich clear cell carcinoma of the breast is a rare histological subtype of breast cancer, accounting for 0.9–2.8% of all breast cancer cases. Fewer than 100 cases have been reported in the literature. Most of these tumors are invasive carcinomas. The intraductal glycogen-rich clear cell carcinoma is a very rare occurrence. Case Report Herein is described a case of a pure intraductal glycogen-rich clear cell carcinoma of the breast in a 42-year-old premenopausal woman. A literature review has also been carried out. Mammography was inconclusive due to the presence of dense breast tissue, but magnetic resonance imaging (MRI) showed several nodular lesions measuring 7 × 6 cm in diameter and involving the upper aspect of the right breast suggestive of multifocal malignancy. A modified radical mastectomy was performed. The patient started hormonal therapy with tamoxifen and is currently well 16 months after surgery. Conclusion A pure intraductal glycogen-rich clear cell carcinoma of the breast is a very rare occurrence. The case presented here exhibited uncommon MRI features, whereas the tumor size is one of the largest reported in the literature. Mammography may be inconclusive in the presence of dense breast tissue, but MRI is of great importance in the preoperative evaluation of the patient. PMID:23904836

A case report of the clear cell variant of gallbladder carcinoma.

PubMed

Maharaj, Ravi; Cave, Christo; Sarran, Kevin; Bascombe, Nigel; Dan, Dilip; Greaves, Wesley; Warner, Wayne A

2017-01-01

Clear cell gallbladder carcinoma accounts for less than 1% of all gallbladder malignancies and demonstrates its unique histopathological characteristics in patients with no prior medical illness or familial predisposition. Here we present a case of a 56-year-old female, with no prior medical conditions presented with a 2-month history of upper abdominal pain. Routine hematological and biochemical tests were unremarkable. An abdominal ultrasound revealed the presence of a gallbladder calculi, and a fundic mass while magnetic resonance cholangiopancreatography revealed a 8.0cm×3.5cm gallbladder mass. Computed tomography imaging excluded any distant haematogenous metastases. An open cholecystectomy with lymphadenectomy was proceeded by staging laparoscopy. Upon pathologic investigation, the morphologic and immunophenotypic features supported a diagnosis of clear cell variant of gallbladder carcinoma. Pathological prognostications for primary clear cell gall bladder carcinomas are not well defined due to the rarity of cases and possible misidentification as secondary metastases. Foci of adenocarcinoma within the tumor along with immunohistochemical staining probes can be informative in consideration of differential diagnosis. In these cases, clinical case management should be personalized for increased survival with the possible incorporation of next generation sequencing approaches to guide therapeutic algorithms. We discuss this exceedingly rare case of the clear cell variant of gallbladder carcinoma in detail, highlighting some of the diagnostic, and clinical challenges. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Renal cell carcinoma in children and young adults: analysis of clinicopathological, immunohistochemical and molecular characteristics with an emphasis on the spectrum of Xp11.2 translocation-associated and unusual clear cell subtypes.

PubMed

Wu, A; Kunju, L P; Cheng, L; Shah, R B

2008-11-01

Recent studies suggest that paediatric renal cell carcinoma (RCC) may represent a distinct group of tumours; however, its biological behaviour and classification remain poorly understood. The aim was to analyse 13 RCCs from patients < or =23 years of age to determine their clinicopathological, immunohistochemical and molecular characteristics. The histological spectrum included: Xp11.2 translocation-associated (6/13 patients, 46%), clear cell (5/13 patients, 38%), papillary (1/13 patients) and unclassified (1/13 patients) types. The Xp11.2 translocation-associated RCCs had a wide morphological spectrum, with high nuclear grade cells with abundant cytoplasm ranging from clear to granular and architecture ranging from solid to papillary. These tumours lacked cytokeratin expression and were confirmed by nuclear reactivity for TFE3 protein. Most of these translocation-associated tumours presented at high stage and had an unfavourable outcome. Three clear cell RCCs had unusual features that have not been previously characterized, including solid and cystic architecture, cells with abundant eosinophilic cytoplasm yet low nuclear grade and focal cytoplasmic inclusions, resembling oncocytoma. Deletion of subtelomeric 3p25 was observed in two of these RCCs. Xp11.2 translocation-associated RCC represents a predominant and aggressive subtype in the paediatric age group. Increased awareness of this subtype is important due to its heterogeneous morphology.

Cutaneous angiosarcoma mimicking xanthoma: a challenging histopathologic diagnosis with important consequences.

PubMed

Llamas-Velasco, Mar; Kutzner, Heinz; Requena, Luis

2016-09-01

Cutaneous angiosarcoma may show protean histopathologic features. Rare or uncommon variants include epithelioid, clear cell, granular cell, verrucous, pseudolymphomatous and signet-ring cell types. Perhaps the rarest type consists of cutaneous angiosarcoma with xanthomization of neoplastic cells. We report an extraordinary case with almost all neoplastic cells exhibiting a xanthomatous appearance that was studied both histopathologically and immunohistochemically. We discuss the histopathologic differential diagnosis of foamy cell angiosarcoma with other neoplasms that may show similar histopathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fallopian tube cytology: a histocorrelative study of 150 washings.

PubMed

Mulvany, N J; Arnstein, M; Ostör, A G

1997-06-01

The aim of the study was to assess the relationship between fallopian tube lavage cytology and recognized microscopic prognostic features in cancer of the uterine corpus. Tubal (TW) and peritoneal washing cytology (PW), endometrial tumor grade, and tumor involvement of the cervix, myometrium, myometrial vessels, and peritoneum were assessed in 150 patients. Endometrioid adenocarcinoma grade I was considered a low-grade tumor, while endometrioid carcinoma grades 2/3, serous/clear cell carcinoma, carcinosarcoma, and high-grade stromal sarcoma were considered high grade. The overall concordance rate for paired TWs and PWs was 72% (108/150). Forward stepwise logistic regression analysis of the 150 tumors revealed that only PWs and cervical involvement were independently predictive of TWs. No relationship was evident between TWs and depth of myometrial invasion, myometrial vascular involvement, or peritoneal metastases. It is concluded that retrograde transtubal spread by malignant endometrial cells occurs independently of myometrial histoprognostic features. TWs provide supporting evidence for diagnostically difficult PWs, and malignant TWs may be detected in the presence of minimally invasive serous/clear cell carcinoma and carcinosarcoma of the endometrium.

EAULIQ: The Next Generation

NASA Technical Reports Server (NTRS)

Randall, David A.; Fowler, Laura D.

1999-01-01

This report summarizes the design of a new version of the stratiform cloud parameterization called Eauliq; the new version is called Eauliq NG. The key features of Eauliq NG are: (1) a prognostic fractional area covered by stratiform cloudiness, following the approach developed by M. Tiedtke for use in the ECMWF model; (2) separate prognostic thermodynamic variables for the clear and cloudy portions of each grid cell; (3) separate vertical velocities for the clear and cloudy portions of each grid cell, allowing the model to represent some aspects of observed mesoscale circulations; (4) cumulus entrainment from both the clear and cloudy portions of a grid cell, and cumulus detrainment into the cloudy portion only; and (5) the effects of the cumulus-induced subsidence in the cloudy portion of a grid cell on the cloud water and ice there. In this paper we present the mathematical framework of Eauliq NG; a discussion of cumulus effects; a new parameterization of lateral mass exchanges between clear and cloudy regions; and a theory to determine the mesoscale mass circulation, based on the hypothesis that the stratiform clouds remain neutrally buoyant through time and that the mesoscale circulations are the mechanism which makes this possible. An appendix also discusses some time-differencing methods.

Analysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection

NASA Astrophysics Data System (ADS)

Sinha, Rileen; Winer, Andrew G.; Chevinsky, Michael; Jakubowski, Christopher; Chen, Ying-Bei; Dong, Yiyu; Tickoo, Satish K.; Reuter, Victor E.; Russo, Paul; Coleman, Jonathan A.; Sander, Chris; Hsieh, James J.; Hakimi, A. Ari

2017-05-01

The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.

PEComa: morphology and genetics of a complex tumor family.

PubMed

Thway, Khin; Fisher, Cyril

2015-10-01

Perivascular epithelioid cell tumors, or PEComas, are mesenchymal neoplasms composed of histologically and immunohistochemically distinctive epithelioid or spindle cells, which are immunoreactive for both smooth muscle and melanocytic markers. The cells in PEComas are typically arranged around blood vessels and appear to form the vessel wall, often infiltrating the smooth muscle of small- to medium-sized vessels. Periluminal cells are usually epithelioid and the more peripheral cells are spindle shaped. The cells have small, round to oval nuclei, sometimes with focal nuclear atypia, and clear to eosinophilic cytoplasm, and no counterpart normal cell has been identified. The PEComa "family" now includes angiomyolipoma, pulmonary clear cell "sugar" tumor and lymphangioleiomyomatosis, primary extrapulmonary sugar tumor, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, abdominopelvic sarcoma of perivascular epithelioid cells, and other tumors with similar features at various sites that are simply termed PEComa. Some PEComas occur in patients with tuberous sclerosis complex and share the genetic abnormalities. There is a behavioral spectrum from benign to frankly malignant, and histologic criteria have been proposed for assessing malignant potential. The differential diagnosis can include carcinomas, smooth muscle tumors, other clear cell neoplasms, and adipocytic tumors. PEComas constitute a genetically diverse group that includes neoplasms harboring TFE3 gene rearrangements and those with TSC2 mutations, indicating alternative tumorigenic pathways. Recent advances in therapy of malignant PEComas relate to increased knowledge of specific genetic changes and their effects on metabolic pathways that are susceptible to specific interventions. We review PEComas, emphasizing the diagnostic spectrum and recent immunohistochemical and genetic findings. Copyright © 2015 Elsevier Inc. All rights reserved.

A Phenotyping Method of Giant Cells from Root-Knot Nematode Feeding Sites by Confocal Microscopy Highlights a Role for CHITINASE-LIKE 1 in Arabidopsis

PubMed Central

Cabrera, Javier; Olmo, Rocio; Ruiz-Ferrer, Virginia; Hermans, Christian; Martinez-Argudo, Isabel; Escobar, Carolina

2018-01-01

Most effective nematicides for the control of root-knot nematodes are banned, which demands a better understanding of the plant-nematode interaction. Understanding how gene expression in the nematode-feeding sites relates to morphological features may assist a better characterization of the interaction. However, nematode-induced galls resulting from cell-proliferation and hypertrophy hinders such observation, which would require tissue sectioning or clearing. We demonstrate that a method based on the green auto-fluorescence produced by glutaraldehyde and the tissue-clearing properties of benzyl-alcohol/benzyl-benzoate preserves the structure of the nematode-feeding sites and the plant-nematode interface with unprecedented resolution quality. This allowed us to obtain detailed measurements of the giant cells’ area in an Arabidopsis line overexpressing CHITINASE-LIKE-1 (CTL1) from optical sections by confocal microscopy, assigning a role for CTL1 and adding essential data to the scarce information of the role of gene repression in giant cells. Furthermore, subcellular structures and features of the nematodes body and tissues from thick organs formed after different biotic interactions, i.e., galls, syncytia, and nodules, were clearly distinguished without embedding or sectioning in different plant species (Arabidopsis, cucumber or Medicago). The combination of this method with molecular studies will be valuable for a better understanding of the plant-biotic interactions. PMID:29389847

Low enhancement on multiphase contrast-enhanced CT images: an independent predictor of the presence of high tumor grade of clear cell renal cell carcinoma.

PubMed

Zhu, Ye-Hua; Wang, Xun; Zhang, Jin; Chen, Yong-Hui; Kong, Wen; Huang, Yi-Ran

2014-09-01

The purpose of this study was to assess the relation between tumor enhancement on multiphase contrast-enhanced CT images and Fuhrman grade of clear cell renal cell carcinoma. A single-institution retrospective review was conducted on the records of 255 patients who underwent radical or partial nephrectomy and received a histologic diagnosis of clear cell renal cell carcinoma. Two radiologists recorded the radiographic features of each patient, including the attenuation value of the lesion, lesion size, calcification within the lesion, cystic versus solid appearance, and margin regularity. Parameters representing the extent of tumor enhancement were defined and calculated. The association between tumor enhancement and Fuhrman grade was analyzed, and multivariate analysis was performed to find independent predictors of high tumor grade. Significant differences existed in tumor enhancement among different Fuhrman grades (p < 0.001). High-grade tumors had significantly lower enhancement (p < 0.001). The enhancement parameter had a sensitivity of 0.84 and specificity of 0.93 in prediction of high tumor grade. In the multivariate analysis, more advanced age, irregular margin, and low tumor enhancement were the three independent predictors of high tumor grade. Tumor enhancement of clear cell renal cell carcinoma on multiphase contrast-enhanced CT images is associated with Fuhrman grade. Low tumor enhancement in the corticomedullary phase is an independent predictor of high tumor grade. This system may be helpful in clinical decision making about the care of patients treated by nonsurgical approaches.

Molecular analysis of mixed endometrial carcinomas shows clonality in most cases

PubMed Central

Hoang, Lien N.; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C. Blake; Lee, Cheng-Han

2016-01-01

Mixed endometrial carcinoma refers to a tumor that is comprised of two or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas - 11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade endometrioid carcinomas (CCC/EC), and 2 mixed clear cell and serous carcinoma (CCC/SC), using targeted next generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC and 1 SC/CCC) showed a serous carcinoma molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch repair protein (MMR) deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and one EC/CCC case showed both shared and unique molecular features in the two histotype components, suggesting early molecular divergence from a common clonal origin. In two cases, there were no shared molecular features and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphological mimicry, whereby tumors with serous-type molecular profile show morphological features of endometrioid or clear cell carcinoma, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors). PMID:26492180

The fundamental role of subcellular topography in peripheral nerve repair therapies.

PubMed

Spivey, Eric C; Khaing, Zin Z; Shear, Jason B; Schmidt, Christine E

2012-06-01

Clinical evidence suggests that nano- and microtopography incorporated into scaffolds does not merely improve peripheral nerve regeneration, but is in fact a prerequisite for meaningful restoration of nerve function. Although the biological mechanisms involved are not fully understood, grafts incorporating physical guides that mimic microscopic nerve tissue features (e.g., basal laminae) appear to provide a significant advantage over grafts that rely on purely chemical or macroscopic similarities to nerve tissue. Investigators consistently demonstrate the fundamental importance of nano- and micro-scale physical features for appropriate cell response in a wide range of biological scenarios. Additionally, recent in vivo research demonstrates that nerve regeneration scaffolds with cell-scale physical features are more effective than those that rely only on chemical or macro-scale features. Physical guidance at the cell-scale is especially important for long (>20 mm) nerve defects, for which the only reliable treatment is the autologous nerve graft. The lack of other available options exposes a clear need for the application of nano- and microfabrication techniques that will allow the next generation of engineered nerve guides to more closely mimic native tissue at those scales. This review examines current research to determine what elements of cell-scale topography in experimental scaffolds are most effective at stimulating functional recovery, and then presents an overview of fabrication techniques that could potentially improve future treatment paradigms. Relative advantages and disadvantages of these techniques are discussed, with respect to both clinical adaptation and likely effectiveness. Our intent is to more clearly delineate the remaining obstacles in the development of a next generation nerve guide, particularly for long defects, and offer new perspectives on steering current technologies towards clinically viable solutions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Atomic Force Microscopy Based Cell Shape Index

NASA Astrophysics Data System (ADS)

Adia-Nimuwa, Usienemfon; Mujdat Tiryaki, Volkan; Hartz, Steven; Xie, Kan; Ayres, Virginia

2013-03-01

Stellation is a measure of cell physiology and pathology for several cell groups including neural, liver and pancreatic cells. In the present work, we compare the results of a conventional two-dimensional shape index study of both atomic force microscopy (AFM) and fluorescent microscopy images with the results obtained using a new three-dimensional AFM-based shape index similar to sphericity index. The stellation of astrocytes is investigated on nanofibrillar scaffolds composed of electrospun polyamide nanofibers that has demonstrated promise for central nervous system (CNS) repair. Recent work by our group has given us the ability to clearly segment the cells from nanofibrillar scaffolds in AFM images. The clear-featured AFM images indicated that the astrocyte processes were longer than previously identified at 24h. It was furthermore shown that cell spreading could vary significantly as a function of environmental parameters, and that AFM images could record these variations. The new three-dimensional AFM-based shape index incorporates the new information: longer stellate processes and cell spreading. The support of NSF PHY-095776 is acknowledged.

Long term imaging of living brain cancer cells

NASA Astrophysics Data System (ADS)

Farias, Patricia M. A.; Galembeck, André; Milani, Raquel; Andrade, Arnaldo C. D. S.; Stingl, Andreas

2018-02-01

QDs synthesized in aqueous medium and functionalized with polyethylene glycol were used as fluorescent probes. They label and monitor living healthy and cancer brain glial cells in culture. Physical-chemical characterization was performed. Toxicological studies were performed by in vivo short and long-term inhalation in animal models. Healthy and cancer glial living cells were incubated in culture media with highly controlled QDs. Specific features of glial cancer cells were enhanced by QD labelling. Cytoplasmic labelling pattern was clearly distinct for healthy and cancer cells. Labelled cells kept their normal activity for same period as non-labelled control samples.

Cytological Study of Grade 3 Endometrioid Adenocarcinoma of Endometrial Origin: Cytoarchitecture and Features of Cell Clusters Assessed With Endometrial Brushing Cytology--Focusing on a comparison with endometrioid adenocarcinoma Grade 1, 2.

PubMed

Matsui, Naruaki; Kajiwara, Hiroshi; Morishita, Akihiro; Tsukada, Hitomi; Nakazawa, Kazumi; Miyazawa, Masaki; Mikami, Mikio; Nakamura, Naoya; Sato, Shinkichi

2015-06-20

Aim of study was to clarify the cytological characteristics of grade 3 endometrioid adenocarcinoma of endometrial origin (G3 EA) by endometrial brushing cytology. The subjects were 11 patients in whom G3 EA was diagnosed by review of preoperative cytological specimens obtained at our hospital and related institutions between 2000 and 2010. These patients were investigated with respect to the preoperative cytological diagnosis, background changes, cell cluster patterns, and individual cellular findings. Background changes were classified as inflammatory or tumorous, while cell clusters were classified as overlapping cell cluster, sheet-like cell cluster, clump of high dense gland, papillary, or other cell cluster. Cellular findings were investigated by comparing the incidence of squamous and clear cell metaplasia, the nuclear rounding rate, and the nuclear area with the findings in a control group (35 patients with G1-2 EA). Background changes were classified as inflammatory in 63.6% and necrotic in 36.4%. The cell clusters were classified as overlapping cell cluster in 44.8%, cell cluster in 21.7%, clump of high dense gland in 10.0%, papillary in 4.0%, and other cell cluster in 19.5%. The incidence of squamous and clear cell metaplasia was 27.2% and 18.1%, respectively. The mean nuclear rounding rate was 0.97, and the mean nuclear area was 55.98 µm2. Investigation of the cytoarchitecture of G3 EA with endometrial brushing cytology revealed overlapping cell cluster and tumor cells of a relatively uniform size. These findings suggest that it is necessary to recognize that there are differences between the cytological findings of G3 EA and the usual features of G1-2 EA.

Coding of spatial attention priorities and object features in the macaque lateral intraparietal cortex.

PubMed

Levichkina, Ekaterina; Saalmann, Yuri B; Vidyasagar, Trichur R

2017-03-01

Primate posterior parietal cortex (PPC) is known to be involved in controlling spatial attention. Neurons in one part of the PPC, the lateral intraparietal area (LIP), show enhanced responses to objects at attended locations. Although many are selective for object features, such as the orientation of a visual stimulus, it is not clear how LIP circuits integrate feature-selective information when providing attentional feedback about behaviorally relevant locations to the visual cortex. We studied the relationship between object feature and spatial attention properties of LIP cells in two macaques by measuring the cells' orientation selectivity and the degree of attentional enhancement while performing a delayed match-to-sample task. Monkeys had to match both the location and orientation of two visual gratings presented separately in time. We found a wide range in orientation selectivity and degree of attentional enhancement among LIP neurons. However, cells with significant attentional enhancement had much less orientation selectivity in their response than cells which showed no significant modulation by attention. Additionally, orientation-selective cells showed working memory activity for their preferred orientation, whereas cells showing attentional enhancement also synchronized with local neuronal activity. These results are consistent with models of selective attention incorporating two stages, where an initial feature-selective process guides a second stage of focal spatial attention. We suggest that LIP contributes to both stages, where the first stage involves orientation-selective LIP cells that support working memory of the relevant feature, and the second stage involves attention-enhanced LIP cells that synchronize to provide feedback on spatial priorities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Hepatic perivascular epithelioid cell tumor (PEComa): dynamic CT, MRI, ultrasonography, and pathologic features--analysis of 7 cases and review of the literature.

PubMed

Tan, Yan; Xiao, En-hua

2012-10-01

To evaluate the dynamic CT, MRI, ultrasonography, and pathologic features of hepatic perivascular epithelioid cell tumor (PEComa), improving the understanding and diagnosis of the tumor. A retrospective analysis of CT, MRI, ultrasonography, and pathologic features of 7 hepatic PEComas diagnosed by pathology during 1st January 2005 to 1st September 2011 in our hospital. The performance of dynamic CT, MRI, and ultrasonography revealed that lesions were regular masses with well-defined borders, the maximum diameters were 2.5-8.5 cm (mean = 4 cm), density was homogeneous, contrast-enhanced CT and MRI showed the lesions were significantly and heterogeneously enhanced on arterial phase, less enhanced on portal venous phase, and slightly hypodense on delayed phase. One patient had multiple hepatic lesions and had delayed enhancement. There were no backgrounds of hepatitis and cirrhosis, enlarged lymph nodes, or distant metastases. Pathology showed the gross appearance of the tumor was smooth. Tumor cells were round or polygonal, with clear boundaries and clear membranes, and had abundant translucent cytoplasm. Nuclei were round, with medium size. Tumor cells were epithelial-like cells and arranged in dense sheets. Immunohistochemistry showed that most of them were positive in HMB45 and MelanA, S-100, SMA, while negative in CgA, Syn, CK, CD117, CD10, and CD34. Dynamic CT, MRI, ultrasonography, and pathology of PEComa had some characteristics of benign tumor's performance. Enhanced scan showed PEComa quickly enhanced on arterial phase and enhanced less on portal venous phase. Knowing these characteristics could help to improve the understanding and diagnosis of hepatic PEComa.

What Everyone Should Know about Archeans

ERIC Educational Resources Information Center

Freeland, Peter

2013-01-01

For many years biologists supposed that one group of microorganisms, which they called archaebacteria, were an ancient and primitive type of bacteria. Following biochemical analysis of their RNA and other cell components, it soon became clear that their distinct features merited classification in a separate domain, the archea. From an evolutionary…

Clear-cell differentiation and lymphatic invasion, but not the revised TNM classification, predict lymph node metastases in pT1 penile cancer: a clinicopathologic study of 76 patients from a low incidence area.

PubMed

Mannweiler, Sebastian; Sygulla, Stephan; Tsybrovskyy, Oleksiy; Razmara, Yas; Pummer, Karl; Regauer, Sigrid

2013-10-01

Prediction of lymph node (LN) metastases in penile invasive cancer relies on clinical features and histologic characteristics of the primary tumor. Correct prediction, however, is difficult, as only 50% patients undergoing lymphadenectomies will have LN metastases. In 2009, the tumor, nodes, metastases (TNM) classification for staging of early penile cancers was revised. We tested the predictive accuracy of the revised TNM classification in a low incidence area for penile carcinoma. The presence of LN metastases in 76 men with pT1 penile cancers was correlated with the 2009 TNM subclassification, which is based on a combined evaluation of tumor grade and lymphatic invasion, but also with individual parameters, such as histologic grade, lymphatic invasion, perineural invasion, invasion depth, growth pattern and human papilloma virus (HPV) status. 76pT1 penile cancers were reclassified into 31pT1a squamous cell carcinomas (SCC) and 45pT1b (41 SCC; 4 clear-cell carcinomas); 12/22 men (55%; 8 SCC, 4 clear-cell carcinomas) undergoing lymphadenectomy for enlarged inguinal lymph nodes had metastases, 54 patients without enlarged LN and lymphadenectomies had no LN metastases during follow-up of median 47 months. Statistically, clear cell differentiation of the primary carcinoma was highly associated with metastases (100% clear-cell carcinomas vs. 11% SCC) and poor survival (50% vs. 5.5%). Among conventional SCC, only lymphatic invasion showed a highly significant association with metastases with 100% specificity. The 2009 TNM classification, tumor grade alone, perineural invasion, growth pattern, invasion depth or HPV status could not predict LN status. Lymphadenectomy for enlarged LN resulted in 100% sensitivity and 42% predictive probability for identifying metastases and a 16% false positive rate. Statistically, survival correlated significantly with clear-cell differentiation and with lymphatic invasion in both clear-cell carcinomas and conventional SCC. Penile clear-cell carcinomas are more aggressive cancers than SCC. Our observation suggests a benefit of a prophylactic lymphadenectomy for patients with clear-cell carcinomas. Among conventional SCC, only lymphatic invasion predicted LN metastases. Neither tumor grade alone nor perineural invasion, growth pattern, depth of invasion, and subgrouping according to the revised TNM classification correlated with metastases. Clinical evaluation of the LN status was superior to histologic risk stratification. Copyright © 2013 Elsevier Inc. All rights reserved.

TFE3 break-apart FISH has a higher sensitivity for Xp11.2 translocation-associated renal cell carcinoma compared with TFE3 or cathepsin K immunohistochemical staining alone: expanding the morphologic spectrum.

PubMed

Rao, Qiu; Williamson, Sean R; Zhang, Shaobo; Eble, John N; Grignon, David J; Wang, Mingsheng; Zhou, Xiao-Jun; Huang, Wenbin; Tan, Puay-Hoon; Maclennan, Gregory T; Cheng, Liang

2013-06-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation is uncommon, characterized by several different translocations involving the TFE3 gene. We assessed the utility of break-apart fluorescence in situ hybridization (FISH) in establishing the diagnosis for suspected or unclassified cases with negative or equivocal TFE3 immunostaining by analyzing 24 renal cancers with break-apart TFE3 FISH and comparing the molecular findings with the results of TFE3 and cathepsin K immunostaining in the same tumors. Ten tumors were originally diagnosed as Xp11.2 RCC on the basis of positive TFE3 immunostaining, and 14 were originally considered unclassified RCCs with negative or equivocal TFE3 staining, but with a range of features suspicious for Xp11.2 RCC. Seventeen cases showed TFE3 rearrangement associated with Xp11.2 translocation by FISH, including all 13 tumors with moderate or strong TFE3 (n=10) or cathepsin K (n=7) immunoreactivity. FISH-positive cases showed negative or equivocal immunoreactivity for TFE3 or cathepsin K in 7 and 10 tumors, respectively (both=3). None had positive immunohistochemistry but negative FISH. Morphologic features were typical for Xp11.2 RCC in 10/17 tumors. Unusual features included 1 melanotic Xp11.2 renal cancer, 1 tumor with mixed features of Xp11.2 RCC and clear cell RCC, and other tumors mimicking clear cell RCC, multilocular cystic RCC, or high-grade urothelial carcinoma. Morphology mimicking high-grade urothelial carcinoma has not been previously reported in these tumors. Psammoma bodies, hyalinized stroma, and intracellular pigment were preferentially identified in FISH-positive cases compared with FISH-negative cases. Our results support the clinical application of a TFE3 break-apart FISH assay for diagnosis and confirmation of Xp11.2 RCC and further expand the histopathologic spectrum of these neoplasms to include tumors with unusual features. A renal tumor with pathologic or clinical features highly suggestive of translocation-associated RCC but exhibiting negative or equivocal TFE3 immunostaining should be evaluated by TFE3 FISH assay to fully assess this possibility.

Pathological significance and prognostic roles of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios in clear cell renal cell carcinoma.

PubMed

Nakanishi, Hiromi; Miyata, Yasuyoshi; Mochizuki, Yasushi; Yasuda, Takuji; Nakamura, Yuichiro; Araki, Kyohei; Sagara, Yuji; Matsuo, Tomohiro; Ohba, Kojiro; Sakai, Hideki

2018-05-19

The immune system is closely associated with malignant behavior in renal cell carcinoma (RCC). Therefore, understanding the pathological roles of immune cells in tumor stroma is essential to discuss the pathological characteristics of RCC. In this study, the clinical significance of densities of CD57+ cells, CD68+ cells, and mast cells, and their ratios were investigated in patients with clear cell RCC. The densities of CD57+, CD68+, and mast cells were evaluated by immunohistochemical techniques in 179 patients. Proliferation index (PI), apoptotic index (AI), and microvessel density (MVD) were evaluated by using anti-Ki-67, anti-cleaved caspase-3, and anti-CD31 antibodies, respectively. The density of CD57+ cell was negatively correlated with grade, pT stage, and metastasis, although densities of CD68+ cell and mast cell were positively correlated. Ratios of CD68+ cell/CD57+ cell and mast cell/CD57+ cell were significantly correlated with grade, pT stage, and metastasis. Survival analyses showed that the CD68+ cell/CD57+ cell ratio was a significant predictor for cause-specific survival by multi-variate analyses (hazard ratio=1.41, 95% confidential interval=1.03-1.93, P=.031), and was significantly correlated with PI, AI, and MVD (r=.47; P <. 001, r=-.31, P<.001, and r=.40, P<.001, respectively). In conclusion, CD57+ cell, CD68+ cell, and mast cell played important roles in malignancy in clear cell RCC. The CD68+ cell/CD57+ cell ratio was strongly correlated with pathological features and prognosis in these patients because this ratio reflected the status of cancer cell proliferation, apoptosis, and angiogenesis. Copyright © 2018. Published by Elsevier Inc.

Cyto-histological correlation of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinoma: Report of a case with review of literature.

PubMed

Manucha, Varsha; Sessums, Mary T; Lewin, Jack; Akhtar, Israh

2018-03-01

The MiT family translocation renal cell carcinomas (RCCs) are relatively rare in comparison to the conventional RCC. The cytologic features overlap with conventional clear cell RCC and papillary RCCs, thereby making the diagnosis extremely challenging. Here, we describe a case of TFE3 translocation associated RCC in a 58-year-old patient, with emphasis on cytomorphologic features and clues toward this diagnostic entity. Correlating the cytohistologic findings and review of touch imprints revealed that presence of hyaline nodules resembling leisegang rings and psammoma bodies in cytologic smears from kidney tumors serve as an important clue in raising a suspicion for the diagnosis of MiT family translocation RCCs. © 2017 Wiley Periodicals, Inc.

Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.

PubMed

Zhou, Ting; Kinney, Marsha C; Scott, Linda M; Zinkel, Sandra S; Rebel, Vivienne I

2015-08-27

Much-needed attention has been given of late to diseases specifically associated with an expanding elderly population. Myelodysplastic syndrome (MDS), a hematopoietic stem cell-based blood disease, is one of these. The lack of clear understanding of the molecular mechanisms underlying the pathogenesis of this disease has hampered the development of efficacious therapies, especially in the presence of comorbidities. Mouse models could potentially provide new insights into this disease, although primary human MDS cells grow poorly in xenografted mice. This makes genetically engineered murine models a more attractive proposition, although this approach is not without complications. In particular, it is unclear if or how myelodysplasia (abnormal blood cell morphology), a key MDS feature in humans, presents in murine cells. Here, we evaluate the histopathologic features of wild-type mice and 23 mouse models with verified myelodysplasia. We find that certain features indicative of myelodysplasia in humans, such as Howell-Jolly bodies and low neutrophilic granularity, are commonplace in healthy mice, whereas other features are similarly abnormal in humans and mice. Quantitative hematopoietic parameters, such as blood cell counts, are required to distinguish between MDS and related diseases. We provide data that mouse models of MDS can be genetically engineered and faithfully recapitulate human disease. © 2015 by The American Society of Hematology.

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder: report of 3 cases and review of the literature.

PubMed

Sukov, William R; Cheville, John C; Amin, Mahul B; Gupta, Ruta; Folpe, Andrew L

2009-02-01

The perivascular epithelioid cell family of tumors (PEComas) includes familiar lesions such as angiomyolipoma, lymphangioleiomyoma, and clear-cell "sugar" tumors of the lung. Less frequently, PEComas arise in various other locations throughout the body including soft tissue, bone, and visceral organs. We report 3 cases of PEComa arising in the urinary bladder in 2 men in their fourth decade, and 1 woman in her third decade. All 3 tumors showed histologic features characteristic of PEComa including spindled and epithelioid cell morphology with variable clear cell change, and all coexpressed melanocytic and smooth muscle associated markers by immunohistochemistry. Follow-up demonstrated an indolent course for 2 patients with no evidence of disease at 10 and 21 months, respectively, and the third case was recently diagnosed. We also provide a review of the 4 previously reported PEComas occurring in the bladder. PEComas of the urinary bladder should be carefully distinguished from a variety of histologically similar, but clinically dissimilar entities.

TFE3 Translocation Associated Perivascular Epithelioid Cell Neoplasm (PEComa) of the Gynecologic Tract: Morphology, Immunophenotype, Differential Diagnosis

PubMed Central

Schoolmeester, J. Kenneth; Dao, Linda N.; Sukov, William R.; Park, Kay J.; Murali, Rajmohan; Hameed, Meera R.; Soslow, Robert A.

2016-01-01

TFE3 translocation associated PEComa is a distinct form of perivascular epithelioid cell neoplasm, the features of which are poorly defined owing to their general infrequency and limited prior reports with confirmed rearrangement or fusion totaling nine cases. Recent investigation has found a lack of TSC gene mutation in these tumors compared to their nonrearranged counterparts which underscores the importance of recognizing the translocated variant due to hypothetical ineffectiveness of targeted mTOR inhibitor therapy. Six cases were identified and TFE3 rearrangement was confirmed by FISH. Patient age ranged 46 to 66 years (median 50) and none had a history of tuberous sclerosis complex. Three cases arose in the uterine corpus, one in the vagina, and one pelvic tumor and one pulmonary tumor were likely a recurrence/metastasis from a probable uterine primary. Five cases had purely clear cell epithelioid morphology that showed a spectrum of atypia while one case had a mixture of clear cell epithelioid and spindle cells. A mostly consistent immunophenotype was observed in the purely clear cell epithelioid cases: each demonstrated diffuse TFE3, HMB45, CathepsinK labeling, either focal or no melanA staining and variably weak reactivity to smooth muscle markers. The mixed clear cell epithelioid and spindle cell case had a similar pattern in its epithelioid component, but strong muscle marker positivity in its spindle cell component. Follow up ranged 1 to 57 months. Three cases demonstrated aggressive behavior and three cases had no evidence of recurrence. Both GYN-specific and traditional sets of criteria for malignancy were evaluated. The GYN model showed improved inclusion and specificity in comparison to the traditional model. PMID:25517951

TFE3 translocation-associated perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: morphology, immunophenotype, differential diagnosis.

PubMed

Schoolmeester, J Kenneth; Dao, Linda N; Sukov, William R; Wang, Lu; Park, Kay J; Murali, Rajmohan; Hameed, Meera R; Soslow, Robert A

2015-03-01

TFE3 translocation-associated PEComa is a distinct form of perivascular epithelioid cell neoplasm, the features of which are poorly defined owing to their general infrequency and limited prior reports with confirmed rearrangement or fusion. Recent investigation has found a lack of TSC gene mutation in these tumors compared with their nonrearranged counterparts, which underscores the importance of recognizing the translocated variant because of hypothetical ineffectiveness of targeted mTOR inhibitor therapy. Six cases were identified, and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Patient age ranged from 46 to 66 years (median 50 y), and none had a history of a tuberous sclerosis complex. Three cases arose in the uterine corpus, 1 in the vagina, 1 pelvic tumor, and 1 pulmonary tumor that was likely a recurrence/metastasis from a probable uterine primary. Five cases had clear cell epithelioid morphology that showed a spectrum of atypia, while 1 case had a mixture of clear cell epithelioid and spindle cells. A mostly consistent immunophenotype was observed in the clear cell epithelioid cases: each demonstrated diffuse TFE3, HMB45, cathepsinK labeling, either focal or no melanA staining, and variably weak reactivity to smooth muscle markers. The mixed clear cell epithelioid and spindle cell case had a similar expression pattern in its epithelioid component but strong muscle marker positivity in its spindle cell component. Follow-up ranged from 1 to 57 months. Three cases demonstrated aggressive behavior, and 3 cases had no evidence of recurrence. Both GYN-specific and traditional sets of criteria for malignancy were evaluated. The GYN model showed improved inclusion and specificity in comparison to the traditional model.

Malignant nodular hidradenoma on the scalp: report of a case with fine needle aspiration cytology features and histologic correlation.

PubMed

Garcia-Bonafe, María Magdalena; Campins, Maria M Company; Redecilla, Pere Huguet

2009-01-01

Malignant nodular hidradenoma (MNH) is a malignant adnexal tumor of the eccrine sweat glands. The histology is similar to that of benign nodular hidradenoma, but MNH shows an infiltrative and invasive pattern, necrosis and angiolymphatic invasion. A 60-year-old woman, diagnosed with rectal adenocarcinoma 6 months before, underwent fine needle aspiration (FNA) of a nodule on the scalp. The aspirate smears showed (1) necrotic debris; (2) cohesive cell clusters and tissue fragments; (3) tubular formations; (4) globoid or cylindrical clear cells; (5) cells showing dense cytoplasm and a basaloid appearance; (6) cell sheets with anaplasia and squamous differentiation; and (7) multinucleated giant cells. The histology showed a lobulated pattern with necrosis and cyst formation. The clear cells that were seen on cytology occupied the periphery of the lobules, whereas the anaplastic cells were located in the central portion. Squamous differentiation and tubular formations were observed. Rapid, accurate diagnosis of these tumors is important, particularly when they develop at sites where a metastatic process must be ruled out. Cytology of FNA material provides this capability.

Ultrastructural characteristics of carcinogen-induced nondysplastic changes in tracheal epithelium.

PubMed Central

Klein-Szanto, A. J.; Topping, D. C.; Heckman, C. A.; Nettesheim, P.

1980-01-01

Nondysplastic hypotrophic and metaplastic epithelial alterations induced by dimethylbenz(a)anthracene in isogenic tracheal transplants were studied by light and electron microscopy 3--24 months after cessation of a 4-week carcinogen exposure. Hypotrophic epithelium observed at all time points was characterized by the presence of nonciliated cells that adopted either cuboidal or squamous shapes, forming simple or bistratified epithelia. Most of these cells, as well as some metaplastic cells, exhibited features of mucin-secreting cells. The metaplastic epithelia showed nonkeratinizing squamous metaplasia, closely related to transitional metaplasia, and keratinizing squamous metaplasia, which presented either an atrophic or an acanthotic epithelium. Although many of these epithelia showed morphologic features of normal stratified epithelia, several nonkeratinizing squamous metaplasias and acanthotic keratinizing squamous metaplasias exhibited some irregularities, probably representing very early atypical ultrastructural features (ie, perinuclear concentration of tonofilament bundles, the presence of dark and clear basal epithelial cells, interruptions and alterations of the basal lamina). These features were not observed in a group of early squamous metaplasias studied for comparative purposes 2 weeks after cessation of dimethylbenz(a)anthracene exposure, which were characterized by a combination of degenerative phenomena and increased cell proliferation. Images Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 14 Figure 15 Figure 6 Figure 7 PMID:6766047

Folliculocentric squamous cell carcinoma with tricholemmal differentiation: a reappraisal of tricholemmal carcinoma.

PubMed

Misago, N; Toda, S; Narisawa, Y

2012-07-01

The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation. To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma. In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2-40] seen in normal hair follicles was retained in the selected lesions. Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34. Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC. © The Author(s). CED © 2012 British Association of Dermatologists.

Feasibility and Biocompatibility of 3D-Printed Photopolymerized and Laser Sintered Polymers for Neuronal, Myogenic, and Hepatic Cell Types.

PubMed

Rimington, Rowan P; Capel, Andrew J; Player, Darren J; Bibb, Richard J; Christie, Steven D R; Lewis, Mark P

2018-06-13

The integration of additive manufacturing (AM) technology within biological systems holds significant potential, specifically when refining the methods utilized for the creation of in vitro models. Therefore, examination of cellular interaction with the physical/physicochemical properties of 3D-printed polymers is critically important. In this work, skeletal muscle (C 2 C 12 ), neuronal (SH-SY5Y) and hepatic (HepG2) cell lines are utilized to ascertain critical evidence of cellular behavior in response to 3D-printed candidate polymers: Clear-FL (stereolithography, SL), PA-12 (laser sintering, LS), and VeroClear (PolyJet). This research outlines initial critical evidence for a framework of polymer/AM process selection when 3D printing biologically receptive scaffolds, derived from industry standard, commercially available AM instrumentation. C 2 C 12 , SH-SY5Y, and HepG2 cells favor LS polymer PA-12 for applications in which cellular adherence is necessitated. However, cell type specific responses are evident when cultured in the chemical leachate of photopolymers (Clear-FL and VeroClear). With the increasing prevalence of 3D-printed biointerfaces, the development of rigorous cell type specific biocompatibility data is imperative. Supplementing the currently limited database of functional 3D-printed biomaterials affords the opportunity for experiment-specific AM process and polymer selection, dependent on biological application and intricacy of design features required. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A case of PSF-TFE3 gene fusion in Xp11.2 renal cell carcinoma with melanotic features.

PubMed

Zhan, He-Qin; Chen, Hong; Wang, Chao-Fu; Zhu, Xiong-Zeng

2015-03-01

Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) with PSF-TFE3 gene fusion is a rare neoplasm. Only 22 cases of Xp11.2 RCCs with PSF-TFE3 have been reported to date. We describe an additional case of Xp11.2 RCC with PSF-TFE3 showing melanotic features. Microscopically, the histologic features mimic clear cell renal cell carcinoma. However, the dark-brown pigments were identified and could be demonstrated as melanins. Immunohistochemically, the tumor cells were widely positive for CD10, human melanoma black 45, and TFE3 but negative for cytokeratins, vimentin, Melan-A, microphthalmia-associated transcription factor, smooth muscle actin, and S-100 protein. Genetically, we demonstrated PSF-TFE3 fusion between exon 9 of PSF and exon 5 of TFE3. The patient was free of disease with 50 months of follow-up. The prognosis of this type of tumor requires more cases because of limited number of cases and follow-up period. Xp11.2 RCC with PSF-TFE3 inevitably requires differentiation from other kidney neoplasms. Immunohistochemical and molecular genetic analyses are essential for accurate diagnosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues.

PubMed

Laskin, William B; Miettinen, Markku

2002-04-01

Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).

Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?

PubMed

Kodiatte, Thomas Alex; George, Sam Varghese; Chacko, Raju Titus; Ramakrishna, Banumathi

2017-01-01

Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.

Ependymal tumors with oligodendroglioma like clear cells: Experience from a tertiary care hospital in Pakistan

PubMed Central

Hashmi, Fauzan Alam; Khan, Muhammad Faheem; Khan, Saad Akhtar; Waqas, Muhammad; Bari, Muhammad Ehsan; Ahmed, Arsalan

2015-01-01

Background: Ependymal tumors with oligodendroglioma like clear cells have never been reported from Pakistan. We aimed to see the features and outcomes of this rare entity. Methods: It was retrospective cohort conducted at the Department of Neurosurgery, Aga Khan University from 2003 to 2013. The medical records and radiology of patients with proven histopathology were reviewed. Analysis was done on SPSS 20. Results: Eleven cases of ependymal tumors with clear cells were found, which equated to 1.5% of the total tumor burden in 11 years. The median age was 49 years. Most common presenting symptom was headache 54.5%. Out of 11 patients, 9 patients had a supratentorial tumor. Magnetic resonance imaging showed hypointense signals on T1 and hyperintense signals on T2-weighted images in all cases. Contrast enhancement was found in 9 patients (77.8%), necrosis and hemorrhage was found in 4 (36%) and 3 (27%) patients, respectively. Immunohistochemistry showed glial fibrillary acidic protein and epithelial membrane antigen positivity in all cases. Ki-67 showed high proliferative index in 6 patients. According to the World Health Organization grading of ependymal tumors, 2 patients had Grade II tumors, and 9 patients had Grade III tumors with clear cells. Gross total resection was achieved in 6 (54.5%) and subtotal resection in 5 patients (45.4%). Recurrence was observed in 9 patients. Six patients died of the disease. Median progression-free survival and overall survival was 8 months and 10 months, respectively. Conclusion: Ependymal tumors with clear cells presented more commonly in Grade III lesions and were more aggressive in behavior with poorer outcome compared to similar studies. PMID:26664928

New pathologic entities in penile carcinomas: an update of the 2004 world health organization classification.

PubMed

Chaux, Alcides; Velazquez, Elsa F; Barreto, José E; Ayala, Enrique; Cubilla, Antonio L

2012-05-01

Most primary malignant tumors of the penis are squamous cell carcinomas (SCC) of the usual type. In recent years several variants, each with distinctive clinicopathologic features, have been described. Pseudohyperplastic carcinoma and carcinoma cuniculatum are both low-grade, extremely well-differentiated SCC variants characterized by an indolent clinical course and good prognosis. The former, which may be confused with pseudoepitheliomatous hyperplasia, preferentially affects the inner foreskin mucosa of elderly men and the latter is a verruciform tumor with an endophytic, burrow-like pattern of growth. Pseudoglandular carcinoma (featuring solid tumor nests with extensive central acantholysis simulating glandular lumina) and clear cell carcinoma (human papillomavirus [HPV]-related tumors composed of periodic acid-Schiff positive clear cells) are aggressive tumors with a high incidence of inguinal nodal metastases. Papillary carcinomas are HPV-unrelated verruciform tumors composed of complex papillae with acanthosis, hyper- and parakeratosis, absence of koilocytes, irregular fibrovascular cores, and jagged tumor base. Finally, in warty-basaloid carcinomas areas of warty (condylomatous) and basaloid carcinomas coexist in the same tumor, either separated or intermingled, giving the tumor a variegated appearance. In this review special emphasis is given to the differential diagnosis of these special variants with a discussion of the possible implications for clinical management.

Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature.

PubMed

Stuart, Lauren N; Tipton, Russell G; DeWall, Michael R; Parker, Douglas C; Stelton, Christina D; Morrison, Annie O; Coleman, Landon W; Fosko, Scott W; Vidal, Claudia I; Yadira Hurley, Maria; Deeken, Amy H; Gardner, Jerad M

2017-08-01

PEComas represent a family of uncommon mesenchymal tumors composed of "perivascular epithelioid cells" with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell "sugar" tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB-45 and/or Melan-A/MART-1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow-up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinicopathologic Characteristics and Prognosis of Xp11.2 Translocation Renal Cell Carcinoma: Multicenter, Propensity Score Matching Analysis.

PubMed

Choo, Min Soo; Jeong, Chang Wook; Song, Cheryn; Jeon, Hwang Gyun; Seo, Seong Il; Hong, Sung Kyu; Byun, Seok-Soo; Chung, Jin Soo; Hong, Sung-Hoo; Hwang, Eu Chang; Kim, Hyeon Hoe; Kwak, Cheol

2017-10-01

We evaluated the clinicopathologic characteristics and prognosis of Xp11.2 translocation (Xp11.2t) renal cell carcinoma (RCC) from a multicenter study and compare them with clear-cell RCC using a propensity score matching analysis. Between 2004 and 2013, 8384 consecutive patients from 7 institutions who were diagnosed with RCC were reviewed, and the pathologically confirmed Xp11.2t cases were enrolled. The oncological outcomes of Xp11.2t were compared with those of clear-cell RCC by selecting matched cases using 1:3 propensity score matching methods in a precollected clear-cell RCC data set from our hospital. The patients were divided into 2 subgroups on the basis of age of onset, either before (early) or after (late) 45 years old. Xp11.2t was found in 61 cases, corresponding to 0.72% of RCC cases for the 10 years. The mean age was 38.2 ± 19.4 years, and the mean tumor size was 6.2 ± 3.9 cm. The Xp11.2t cases were at more advanced stages and showed tendencies to involve lymph nodes at diagnosis. After the matching, there were no significant differences in recurrence-free and overall survival compared with clear-cell RCC. The age of incidence for Xp11.2t had a bimodal distribution, which was most common in the 30s and smaller peak in the 60s. Xp11.2t corresponded to a significantly worse prognosis for overall survival in late onset (after 45 years) subgroup (P = .038; hazard ratio, 3.199; 95% confidence interval, 1.065-9.609). This neoplasm has more aggressive clinicopathologic features at diagnosis. In older patients with onset age > 45 years, Xp11.2t showed a significantly worse prognosis than clear-cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

IR spectroscopic characteristics of cell cycle and cell death probed by synchrotron radiation based Fourier transform IR spectromicroscopy

NASA Technical Reports Server (NTRS)

Holman, H. Y.; Martin, M. C.; Blakely, E. A.; Bjornstad, K.; McKinney, W. R.

2000-01-01

Synchrotron radiation based Fourier transform IR (SR-FTIR) spectromicroscopy allows the study of individual living cells with a high signal to noise ratio. Here we report the use of the SR-FTIR technique to investigate changes in IR spectral features from individual human lung fibroblast (IMR-90) cells in vitro at different points in their cell cycle. Clear changes are observed in the spectral regions corresponding to proteins, DNA, and RNA as a cell changes from the G(1)-phase to the S-phase and finally into mitosis. These spectral changes include markers for the changing secondary structure of proteins in the cell, as well as variations in DNA/RNA content and packing as the cell cycle progresses. We also observe spectral features that indicate that occasional cells are undergoing various steps in the process of cell death. The dying or dead cell has a shift in the protein amide I and II bands corresponding to changing protein morphologies, and a significant increase in the intensity of an ester carbonyl C===O peak at 1743 cm(-1) is observed. Copyright John Wiley & Sons, Inc. Biopolymers (Biospectroscopy) 57: 329-335, 2000.

Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy

PubMed Central

Docheva, Denitsa; Padula, Daniela; Popov, Cvetan; Mutschler, Wolf; Clausen-Schaumann, Hauke; Schieker, Matthias

2008-01-01

Abstract Within the bone lie several different cell types, including osteoblasts (OBs) and mesenchymal stem cells (MSCs). The MSCs are ideal targets for regenerative medicine of bone due to their differentiation potential towards OBs. Human MSCs exhibit two distinct morphologies: rapidly self-renewing cells (RS) and flat cells (FC) with very low proliferation rates. Another cell type found in pathological bone conditions is osteosarcoma. In this study, we compared the topographic and morphometric features of RS and FC cells, human OBs and MG63 osteosarcoma cells by atomic force microscopy (AFM). The results demonstrated clear differences: FC and hOB cells showed similar ruffled topography, whereas RS and MG63 cells exhibited smoother surfaces. Furthermore, we investigated how selected substrates influence cell morphometry. We found that RS and MG63 cells were flatter on fibrous substrates such as polystyrene and collagen I, but much more rounded on glass, the smoothest surface. In contrast, cells with large area, namely FC and hOB cells, did not exhibit pronounced changes in flatness with regards to the different substrates. They were, however, remarkably flatter in comparison to RS and MG63 cells. We could explain the differences in flatness by the extent of adhesion. Indeed, FC and hOB cells showed much higher content of focal adhesions. Finally, we used the AFM to determine the cellular Young's modulus. RS, FC and hOB cells showed comparable stiffness on the three different substrates, while MG63 cells demonstrated the unique feature of increased elasticity on collagen I. In summary, our results show, for the first time, a direct comparison between the morphometric and biophysical features of different human cell types derived from normal and pathological bone. Our study manifests the opinion that along with RNA, proteomic and functional research, morphological and biomechanical characterization of cells also reveals novel cell features and interrelationships. PMID:18419596

Radiotherapy on hidradenocarcinoma.

PubMed

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. POST OPERATIVE RADIOTHERAPY ALLOWS BETTER LOCAL CONTROL AND SHOULD BE MANDATORY WHEN HISTOLOGICAL FEATURES PREDICTIVE OF RECURRENCE ARE PRESENT: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread.

[IgG4-related disease].

PubMed

González-Moreno, Juan; Losada López, Inés; Ortego Centeno, Norberto

2015-12-21

IgG4-related disease is a recently described clinicopathological entity showing a wide spectrum of clinical manifestations that share a common pathology. Its most characteristic feature is the formation of inflammatory tumors in different organs, which makes differentiation mainly with neoplastic diseases fundamental. The inflammatory process is typically comprised of IgG4 lymphoplasmacytic cells. The pathophysiological role of the immunoglobulin is not clear. The treatment of choice is corticosteroids. This article aims to summarize the main features of the disease. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Molecular-genetic analysis is essential for accurate classification of renal carcinoma resembling Xp11.2 translocation carcinoma.

PubMed

Hayes, Malcolm; Peckova, Kvetoslava; Martinek, Petr; Hora, Milan; Kalusova, Kristyna; Straka, Lubomir; Daum, Ondrej; Kokoskova, Bohuslava; Rotterova, Pavla; Pivovarčikova, Kristyna; Branzovsky, Jindrich; Dubova, Magdalena; Vesela, Pavla; Michal, Michal; Hes, Ondrej

2015-03-01

Xp11.2-translocation renal carcinoma (TRCC) is suspected when a renal carcinoma occurs in young patients, patients with a prior history of exposure to chemotherapy and when the neoplasm has morphological features suggestive of that entity. We retrieved 20 renal tumours (from 17,500 archival cases) of which morphology arose suspicion for TRCC. In nine cases, TFE3 translocation was confirmed by fluorescence in situ hybridisation analysis. In 9 of the remaining 11 TRCC-like cases (7 male, 4 female, aged 22-84 years), material was available for further study. The morphological spectrum was diverse. Six tumours showed a mixture of cells with eosinophilic or clear cytoplasm in tubular, acinar and papillary architecture. One case was high grade with epithelioid, spindle cell and sarcomatoid areas. Another showed tubular, solid, and papillary areas and foci containing spindle cells reminiscent of mucinous tubular and spindle cell carcinoma. The third showed dyscohesive nests of large epithelioid and histiocytoid cells in a background of dense lymphoplasmacytic infiltrate. By immunohistochemistry, keratin AE1/AE3 was diffusely positive in three tumours, while CK7 strongly stained one tumour and another focally and weakly. CD10 and Pax8 were expressed by eight, AMACR and vimentin by seven, CA-IX by four and TFE3 and cathepsin K by two tumours. Of the two TFE3-positive tumours, one showed polysomy of chromosome 7 and the other of 17; they were VHL normal and diagnosed as unclassifiable RCC. Of the seven TFE3-negative tumours, three showed polysomy of 7/17 and VHL abnormality and were diagnosed as combined clear cell RCC/papillary RCC. One TFE3-negative tumour with normal 7/17 but LOH 3p (VHL abnormality) was diagnosed as clear cell RCC. One TFE3-negative tumour with polysomy 7/17 but normal VHL was diagnosed as papillary RCC, and two with normal chromosomes 7/17 and VHL gene were considered unclassifiable. As morphological features and IHC are heterogeneous, TRCC-like renal tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis.

probing the atmosphere with high power, high resolution radars

NASA Technical Reports Server (NTRS)

Hardy, K. R.; Katz, I.

1969-01-01

Observations of radar echoes from the clear atmosphere are presented and the scattering mechanisms responsible for the two basic types of clear-air echoes are discussed. The commonly observed dot echo originates from a point in space and usually shows little variation in echo intensity over periods of about 0.1 second. The second type of clear-air radar echo appears diffuse in space, and signal intensities vary considerably over periods of less than 0.1 second. The echoes often occur in thin horizontal layers or as boundaries of convective activity; these are characterized by sharp gradients of refractive index. Some features of clear-air atmospheric structures as observed with radar are presented. These structures include thin stable inversions, convective thermals, Benard convection cells, breaking gravity waves, and high tropospheric layers which are sufficiently turbulent to affect aircraft.

Roles of GSK3 in metabolic shift toward abnormal anabolism in cell senescence.

PubMed

Kim, You-Mie; Seo, Yong-Hak; Park, Chan-Bae; Yoon, Soo-Han; Yoon, Gyesoon

2010-07-01

Diverse metabolic alterations, including mitochondrial dysfunction, have often been reported as characteristic phenotypes of senescent cells. However, the overall consequence of senescent metabolic features, how they develop, and how they are linked to other senescent phenotypes, such as enlarged cell volume, increased granularity, and oxidative stress, is not clear. We investigated the potential roles of glycogen synthase kinase 3 (GSK3), a multifunctional kinase, in the development of the metabolic phenotypes in cell senescence. The inactivation of GSK3 via phosphorylation is commonly observed in diverse cell senescences. Furthermore, subcytotoxic concentration of GSK3 inhibitor was sufficient to induce cellular senescence, accompanied by augmented anabolism, such as enhanced protein synthesis, and increased glycogenesis and lipogenesis, in addition to mitochondrial dysfunction. Anabolism was accomplished through glycogen synthase, eIF2B, and SREBP1. These metabolic features seem to contribute to an increase in cellular mass by increasing glycogen granules, protein mass, and organelles. Taken together, our results suggest that GSK3 is one of the key modulators of metabolic alteration, leading the cells to senescence.

Mouse strain and injection site are crucial for detecting linked suppression in transplant recipients by trans-vivo DTH assay.

PubMed

Burlingham, W J; Jankowska-Gan, E

2007-02-01

Chemokine-driven accumulation of lymphocytes, mononuclear and polymorphonuclear proinflammatory cells in antigenic tissue sites is a key feature of several types of T-cell-dependent autoimmunity and transplant rejection pathology. It is now clear that the immune system expends considerable energy to control this process, exemplified by the sequential layers of regulatory cell input, both innate and adaptive, designed to prevent a classical Type IV or 'delayed-type' hypersensitivity (DTH) reaction from occurring in the visual field of the eye. Yet, despite an abundance of in vitro assays currently available to the human T-cell immunologist, none of them adequately models the human DTH response and its various control features. The theme of this article is that it is relatively easy to model the effector side of the human DTH response with xenogeneic adoptive transfer models. However, we show that in order to detect inhibition of a recall DTH in response to colocalized donor antigen (linked suppression)--a characteristic feature of peripheral tolerance to an organ transplant--both the challenge site and the immunocompetence of the mouse adoptive host are critical factors limiting the sensitivity of the trans-vivo DTH test.

[Knockdown of ATG5 enhances the sensitivity of human renal carcinoma cells to sunitinib].

PubMed

Li, Peng; Han, Qi; Tang, Ming; Zhang, Keqin

2017-03-01

Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown. Proliferation rate of A-498 cells in control group and ATG5 low expression group was determined by flow cytometry. Finally, the survival rate was detected by MTT assay after A-498 cells were treated with different concentrations of sunitinib. Results The expression levels of ATG5 and LC3 in renal clear cell carcinoma tissues were significantly higher than those in para-tumor tissues. The expression levels of ATG5 and LC3 were associated with classification, histological grade, TNM stage and survival rate, rather than gender, age, location, tumor size. Compared with the control group, the protein expressions of ATG5 and LC3 significantly decreased in A-498 cells with ATG5 low expression. The cell proliferation rate in ATG5 downregulation group was lower than that in the control group. Compared with control group, the survival rate in ATG5 low expression group were significantly reduced in a dose-dependent manner after sunitinib treatment. Conclusion Autophagy is active in renal clear cell carcinoma, and the drug sensitivity to sunitinib in renal cancer cells can be enhanced by the downregulation of ATG5.

Extraction of multi-scale landslide morphological features based on local Gi* using airborne LiDAR-derived DEM

NASA Astrophysics Data System (ADS)

Shi, Wenzhong; Deng, Susu; Xu, Wenbing

2018-02-01

For automatic landslide detection, landslide morphological features should be quantitatively expressed and extracted. High-resolution Digital Elevation Models (DEMs) derived from airborne Light Detection and Ranging (LiDAR) data allow fine-scale morphological features to be extracted, but noise in DEMs influences morphological feature extraction, and the multi-scale nature of landslide features should be considered. This paper proposes a method to extract landslide morphological features characterized by homogeneous spatial patterns. Both profile and tangential curvature are utilized to quantify land surface morphology, and a local Gi* statistic is calculated for each cell to identify significant patterns of clustering of similar morphometric values. The method was tested on both synthetic surfaces simulating natural terrain and airborne LiDAR data acquired over an area dominated by shallow debris slides and flows. The test results of the synthetic data indicate that the concave and convex morphologies of the simulated terrain features at different scales and distinctness could be recognized using the proposed method, even when random noise was added to the synthetic data. In the test area, cells with large local Gi* values were extracted at a specified significance level from the profile and the tangential curvature image generated from the LiDAR-derived 1-m DEM. The morphologies of landslide main scarps, source areas and trails were clearly indicated, and the morphological features were represented by clusters of extracted cells. A comparison with the morphological feature extraction method based on curvature thresholds proved the proposed method's robustness to DEM noise. When verified against a landslide inventory, the morphological features of almost all recent (< 5 years) landslides and approximately 35% of historical (> 10 years) landslides were extracted. This finding indicates that the proposed method can facilitate landslide detection, although the cell clusters extracted from curvature images should be filtered using a filtering strategy based on supplementary information provided by expert knowledge or other data sources.

BRAF and MEK inhibitor therapy eliminates nestin expressing melanoma cells in human tumors.

PubMed

Doxie, Deon B; Greenplate, Allison R; Gandelman, Jocelyn S; Diggins, Kirsten E; Roe, Caroline E; Dahlman, Kimberly B; Sosman, Jeffrey A; Kelley, Mark C; Irish, Jonathan M

2018-05-19

Little is known about the in vivo impacts of targeted therapy on melanoma cell abundance and protein expression. Here, 21 antibodies were added to an established melanoma mass cytometry panel to measure 32 cellular features, distinguish malignant cells, and characterize dabrafenib and trametinib responses in BRAF V 600mut melanoma. Tumor cells were biopsied before neoadjuvant therapy and compared to cells surgically resected from the same site after 4 weeks of therapy. Approximately 50,000 cells per tumor were characterized by mass cytometry and computational tools t-SNE/viSNE, FlowSOM, and MEM. The resulting single cell view of melanoma treatment response revealed initially heterogeneous melanoma tumors were consistently cleared of Nestin expressing melanoma cells. Melanoma cells subsets that persisted to week 4 were heterogeneous but expressed SOX2 or SOX10 proteins and specifically lacked surface expression of MHC I proteins by MEM analysis. Traditional histology imaging of tissue microarrays from the same tumors confirmed mass cytometry results, including persistence of NES- SOX10+ S100β+ melanoma cells. This quantitative single cell view of melanoma treatment response revealed protein features of malignant cells that are not eliminated by targeted therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Radiotherapy on hidradenocarcinoma

PubMed Central

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Context: Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. Case Report: We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. Conclusion: Post operative radiotherapy allows better local control and should be mandatory when histological features predictive of recurrence are present: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread. PMID:22540063

Immunohistochemical characterization of endometrial carcinomas: endometrioid, serous and clear cell adenocarcinomas in association with genetic analysis.

PubMed

Yasuda, Masanori

2014-12-01

Developments in immunohistochemistry, which are closely linked with the advances in the analyses of genetic abnormalities and their associated molecular disorders as early and late histogenetic events, have contributed greatly to the improvement of pathological diagnostic confirmation and validation. Immunohistochemistry has also generated great benefit to the innovation of therapeutic strategies for various kinds of cancers. In this article, the three representative histological types of corpus cancer, namely, endometrioid adenocarcinoma, serous adenocarcinoma and clear cell adenocarcinoma, will be histologically approached in association with their immunohistochemical profiles as well as genetic disorders. First, the focus will be on 'Conventional/prototypic features,' followed by 'Controversy over conventional histological subclassification,' and subsequently 'Tumorigenesis and re-subclassification'. © 2014 The Author. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Enhancing facial features by using clear facial features

NASA Astrophysics Data System (ADS)

Rofoo, Fanar Fareed Hanna

2017-09-01

The similarity of features between individuals of same ethnicity motivated the idea of this project. The idea of this project is to extract features of clear facial image and impose them on blurred facial image of same ethnic origin as an approach to enhance a blurred facial image. A database of clear images containing 30 individuals equally divided to five different ethnicities which were Arab, African, Chines, European and Indian. Software was built to perform pre-processing on images in order to align the features of clear and blurred images. And the idea was to extract features of clear facial image or template built from clear facial images using wavelet transformation to impose them on blurred image by using reverse wavelet. The results of this approach did not come well as all the features did not align together as in most cases the eyes were aligned but the nose or mouth were not aligned. Then we decided in the next approach to deal with features separately but in the result in some cases a blocky effect was present on features due to not having close matching features. In general the available small database did not help to achieve the goal results, because of the number of available individuals. The color information and features similarity could be more investigated to achieve better results by having larger database as well as improving the process of enhancement by the availability of closer matches in each ethnicity.

Time-lapse electrical impedance spectroscopy for monitoring the cell cycle of single immobilized S. pombe cells.

PubMed

Zhu, Zhen; Frey, Olivier; Haandbaek, Niels; Franke, Felix; Rudolf, Fabian; Hierlemann, Andreas

2015-11-26

As a complement and alternative to optical methods, wide-band electrical impedance spectroscopy (EIS) enables multi-parameter, label-free and real-time detection of cellular and subcellular features. We report on a microfluidics-based system designed to reliably capture single rod-shaped Schizosaccharomyces pombe cells by applying suction through orifices in a channel wall. The system enables subsequent culturing of immobilized cells in an upright position, while dynamic changes in cell-cycle state and morphology were continuously monitored through EIS over a broad frequency range. Besides measuring cell growth, clear impedance signals for nuclear division have been obtained. The EIS system has been characterized with respect to sensitivity and detection limits. The spatial resolution in measuring cell length was 0.25 μm, which corresponds to approximately a 5-min interval of cell growth under standard conditions. The comprehensive impedance data sets were also used to determine the occurrence of nuclear division and cytokinesis. The obtained results have been validated through concurrent confocal imaging and plausibilized through comparison with finite-element modeling data. The possibility to monitor cellular and intracellular features of single S. pombe cells during the cell cycle at high spatiotemporal resolution renders the presented microfluidics-based EIS system a suitable tool for dynamic single-cell investigations.

Time-lapse electrical impedance spectroscopy for monitoring the cell cycle of single immobilized S. pombe cells

PubMed Central

Zhu, Zhen; Frey, Olivier; Haandbaek, Niels; Franke, Felix; Rudolf, Fabian; Hierlemann, Andreas

2015-01-01

As a complement and alternative to optical methods, wide-band electrical impedance spectroscopy (EIS) enables multi-parameter, label-free and real-time detection of cellular and subcellular features. We report on a microfluidics-based system designed to reliably capture single rod-shaped Schizosaccharomyces pombe cells by applying suction through orifices in a channel wall. The system enables subsequent culturing of immobilized cells in an upright position, while dynamic changes in cell-cycle state and morphology were continuously monitored through EIS over a broad frequency range. Besides measuring cell growth, clear impedance signals for nuclear division have been obtained. The EIS system has been characterized with respect to sensitivity and detection limits. The spatial resolution in measuring cell length was 0.25 μm, which corresponds to approximately a 5-min interval of cell growth under standard conditions. The comprehensive impedance data sets were also used to determine the occurrence of nuclear division and cytokinesis. The obtained results have been validated through concurrent confocal imaging and plausibilized through comparison with finite-element modeling data. The possibility to monitor cellular and intracellular features of single S. pombe cells during the cell cycle at high spatiotemporal resolution renders the presented microfluidics-based EIS system a suitable tool for dynamic single-cell investigations. PMID:26608589

Interplay between YB-1 and IL-6 promotes the metastatic phenotype in breast cancer cells.

PubMed

Castellana, Bàrbara; Aasen, Trond; Moreno-Bueno, Gema; Dunn, Sandra E; Ramón y Cajal, Santiago

2015-11-10

Epithelial to mesenchymal transition (EMT) induces cell plasticity and promotes metastasis. The multifunctional oncoprotein Y-box binding protein-1 (YB-1) and the pleiotropic cytokine interleukin 6 (IL-6) have both been implicated in tumor cell metastasis and EMT, but via distinct pathways. Here, we show that direct interplay between YB-1 and IL-6 regulates breast cancer metastasis. Overexpression of YB-1 in breast cancer cell lines induced IL-6 production while stimulation with IL-6 increased YB-1 expression and YB-1 phosphorylation. Either approach was sufficient to induce EMT features, including increased cell migration and invasion. Silencing of YB-1 partially reverted the EMT and blocked the effect of IL-6 while inhibition of IL-6 signaling blocked the phenotype induced by YB-1 overexpression, demonstrating a clear YB-1/IL-6 interdependence. Our findings describe a novel signaling network in which YB-1 regulates IL-6, and vice versa, creating a positive feed-forward loop driving EMT-like metastatic features during breast cancer progression. Identification of signaling partners or pathways underlying this co-dependence may uncover novel therapeutic opportunities.

Membrane traffic and synaptic cross-talk during host cell entry by Trypanosoma cruzi.

PubMed

Butler, Claire E; Tyler, Kevin M

2012-09-01

It is widely accepted that Trypanosoma cruzi can exploit the natural exocytic response of the host to cell damage, utilizing host cell lysosomes as important effectors. It is, though, increasingly clear that the parasite also exploits endocytic mechanisms which allow for incorporation of plasma membrane into the parasitophorous vacuole. Further, that these endocytic mechanisms are involved in cross-talk with the exocytic machinery, in the recycling of vesicles and in the manipulation of the cytoskeleton. Here we review the mechanisms by which T. cruzi exploits features of the exocytic and endocytic pathways in epithelial and endothelial cells and the evidence for cross-talk between these pathways. © 2012 Blackwell Publishing Ltd.

Mouse model for acute Epstein-Barr virus infection.

PubMed

Wirtz, Tristan; Weber, Timm; Kracker, Sven; Sommermann, Thomas; Rajewsky, Klaus; Yasuda, Tomoharu

2016-11-29

Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas. We have modeled acute EBV infection of naive and GC B cells in mice through timed expression of LMP1 and LMP2A. Although lethal when induced in all B cells, induction of LMP1 and LMP2A in just a small fraction of naive B cells initiated a phase of rapid B-cell expansion followed by a proliferative T-cell response, clearing the LMP-expressing B cells. Interfering with T-cell activity prevented clearance of LMP-expressing B cells. This was also true for perforin deficiency, which in the human causes a life-threatening EBV-related immunoproliferative syndrome. LMP expression in GC B cells impeded the GC reaction but, upon loss of T-cell surveillance, led to fatal B-cell expansion. Thus, timed expression of LMP1 together with LMP2A in subsets of mouse B cells allows one to study major clinically relevant features of human EBV infection in vivo, opening the way to new therapeutic approaches.

The histological diagnosis of metastases to the breast from extramammary malignancies

PubMed Central

Lee, Andrew H S

2007-01-01

This study aims to review histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. Histological features were compared between non‐haematological metastases to the breast and 100 consecutive core biopsy specimens of primary invasive carcinomas of the breast. 18 non‐haematological metastases to the breast were diagnosed over a 10‐year period (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen only in primary mammary cancers. Two‐thirds of tumours had features raising the possibility of metastasis, such as clear cell carcinoma suggestive of renal origin and small cell carcinoma suggestive of pulmonary origin. The features observed in haematological metastases are also described. Immunohistochemical panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid protein‐15) from common metastases to the breast, including carcinoma of the lung (thyroid transcription factor‐1), malignant melanoma (S100, HMB45, melan‐A) and ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The pathologist has a key role in considering the diagnosis of metastasis to the breast if the histological features are unusual for a primary mammary tumour. The clinical history is vital in some cases. Immunohistochemistry plays a useful supplementary role. PMID:18042689

The histological diagnosis of metastases to the breast from extramammary malignancies.

PubMed

Lee, Andrew H S

2007-12-01

This study aims to review histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. Histological features were compared between non-haematological metastases to the breast and 100 consecutive core biopsy specimens of primary invasive carcinomas of the breast. 18 non-haematological metastases to the breast were diagnosed over a 10-year period (0.3% of malignant mammary tumours). Elastosis and carcinoma in situ were seen only in primary mammary cancers. Two-thirds of tumours had features raising the possibility of metastasis, such as clear cell carcinoma suggestive of renal origin and small cell carcinoma suggestive of pulmonary origin. The features observed in haematological metastases are also described. Immunohistochemical panels to distinguish mammary carcinoma (oestrogen receptor, gross cystic fluid protein-15) from common metastases to the breast, including carcinoma of the lung (thyroid transcription factor-1), malignant melanoma (S100, HMB45, melan-A) and ovarian serous papillary carcinoma (Wilms' tumour 1), are discussed. The pathologist has a key role in considering the diagnosis of metastasis to the breast if the histological features are unusual for a primary mammary tumour. The clinical history is vital in some cases. Immunohistochemistry plays a useful supplementary role.

The many faces and mimics of papillary thyroid carcinoma.

PubMed

Albores-Saavedra, Jorge; Wu, Jianhua

2006-01-01

This article provides an overview of the 15 histologic variants of papillary thyroid carcinoma listed by the 2004 World Health Organization (WHO) monograph on endocrine tumors. The histologic features, differential diagnosis, and clinical course of each variant are discussed in some detail. The follicular variants (conventional and macrofollicular) constitute a morphologic challenge because the majority of these tumors are encapsulated and, also, because, in many tumors, not all neoplastic cells show the nuclear features considered to be diagnostic of papillary carcinoma. As a result, most of these tumors are missed even by experienced pathologists. Moreover, hyperplastic thyroid lesions, follicular adenomas, and Hashimoto's thyroiditis may contain cells with clear nuclei resembling those of papillary carcinoma. Papillary carcinomas composed entirely of hyperchromatic cells have been overlooked. The WHO monograph defines papillary carcinoma with focal spindle and giant cell carcinoma components but its clinical behavior is unknown. Papillary carcinoma with an insular pattern that does not show the artifactual separation of the cell nests has been misinterpreted as the solid variant of papillary carcinoma. Papillary microcarcinomas include not only the conventional type and the follicular variants but also the tall cell and columnar cell variants.

Leukemia-lymphoma cell lines as model systems for hematopoietic research.

PubMed

Drexler, Hans G; MacLeod, Roderick A F

2003-01-01

Continuous human leukemia-lymphoma (LL) cell lines comprise a rich self-renewing resource of accessible and manipulable living cells which has illuminated the pathophysiology of hematopoietic tumors as well as basic cell biology. The major key advantages of continuous cell lines are the unlimited supply and worldwide availability of identical cell material and their cryopreservation. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro with preservation of most cellular features, and specific genetic alterations. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines may be distinguished from Epstein-Barr virus (EBV)-immortalized normal cells, using various operational and conceptual parameters. The characterization and publication of new LL cell lines provides important and informative core data which, by opening new avenues for investigation, have become ubiquitous powerful research tools that are available to every investigator by reference cell repositories. There is a need in the scientific community for clean and authenticated LL cell lines to which every scientist has access as offered by these institutionalized public cell line banks. A list of the most useful, robust and freely available reference cell lines is proposed in this review. Clearly, studies of LL cell lines have provided seminal insights into the biology of hematopoietic neoplasia.

Confocal Fluorescence Microscopy of Mung Beanleaves

NASA Astrophysics Data System (ADS)

Chen, Zhiwei; Liu, Dongwu

Recently, confocal microscope has become a routine technique and indispensable tool for cell biological studies and molecular investigations. The light emitted from the point out-of-focus is blocked by the pinhole and can not reach the detector, which is one of the critical features of the confocal microscope. In present studies, the probes acridine orange (AO) and rhodamine-123 were used to research stoma and mitochondria of mung bean leaves, respectively. The results indicated that the stomatal guard cells and mitochondria were clearly seen in epidermic tissue of mung bean leaves. Taken together, it is a good method to research plant cells with confocal microscope and fluorescence probes.

Dynamic Computed Tomographic Features of Adult Renal Cell Carcinoma Associated With Xp11.2 Translocation/TFE3 Gene Fusions: Comparison With Clear Cell Renal Cell Carcinoma.

PubMed

He, Jian; Gan, Weidong; Liu, Song; Zhou, Kefeng; Zhang, Gutian; Guo, Hongqian; Zhu, Bin

2015-01-01

To investigate the dynamic contrast-enhanced computed tomography (CT) characteristics of renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusion (Xp11.2 RCC) by comparison with clear cell renal cell carcinoma (CCRCC). Dynamic contrast-enhanced CT images and clinical and pathological records of 20 adult patients with Xp11.2 RCC confirmed by TFE3 immunohistochemical and fluorescence in situ hybridization assay were retrospectively analyzed and compared with the findings of 21 contemporary CCRCCs. Renal cell carcinoma associated with Xp11.2 translocation and TFE gene fusions often occurred in young (30.6 ± 8.6 years) patients with hematuria (9/20). They presented as well-defined (17/20) cystic-solid (17/20) mass with hemorrhage (8/20) and circular/rim calcifications (6/20). Dynamic contrast-enhanced CT showed heterogeneous moderate prolonged enhancement. A tumor-to-cortex attenuation ratio in corticomedullary phase less than 0.62 gave a sensitivity of 90.0% and a specificity of 92.9% in differentiating Xp11.2 RCC from CCRCC (area under the receiver operating characteristic curve = 0.957, P < 0.001). Computed tomographic characteristics and dynamic contrast-enhanced patterns and index can differentiate Xp11.2 RCC from CCRCC.

Selective plane illumination microscopy (SPIM) with time-domain fluorescence lifetime imaging microscopy (FLIM) for volumetric measurement of cleared mouse brain samples

NASA Astrophysics Data System (ADS)

Funane, Tsukasa; Hou, Steven S.; Zoltowska, Katarzyna Marta; van Veluw, Susanne J.; Berezovska, Oksana; Kumar, Anand T. N.; Bacskai, Brian J.

2018-05-01

We have developed an imaging technique which combines selective plane illumination microscopy with time-domain fluorescence lifetime imaging microscopy (SPIM-FLIM) for three-dimensional volumetric imaging of cleared mouse brains with micro- to mesoscopic resolution. The main features of the microscope include a wavelength-adjustable pulsed laser source (Ti:sapphire) (near-infrared) laser, a BiBO frequency-doubling photonic crystal, a liquid chamber, an electrically focus-tunable lens, a cuvette based sample holder, and an air (dry) objective lens. The performance of the system was evaluated with a lifetime reference dye and micro-bead phantom measurements. Intensity and lifetime maps of three-dimensional human embryonic kidney (HEK) cell culture samples and cleared mouse brain samples expressing green fluorescent protein (GFP) (donor only) and green and red fluorescent protein [positive Förster (fluorescence) resonance energy transfer] were acquired. The results show that the SPIM-FLIM system can be used for sample sizes ranging from single cells to whole mouse organs and can serve as a powerful tool for medical and biological research.

Methuosis

PubMed Central

Maltese, William A.; Overmeyer, Jean H.

2015-01-01

Apoptosis is the most widely recognized form of physiological programmed cell death. During the past three decades, various nonapoptotic forms of cell death have gained increasing attention, largely because of their potential importance in pathological processes, toxicology, and cancer therapy. A recent addition to the panoply of cell death phenotypes is methuosis. The neologism is derived from the Greek methuo (to drink to intoxication) because the hallmark of this form of cell death is displacement of the cytoplasm by large fluid-filled vacuoles derived from macropinosomes. The demise of the cell resembles many forms of necrosis, insofar as there is a loss of metabolic capacity and plasma membrane integrity, without the cell shrinkage and nuclear fragmentation associated with apoptosis. Methuosis was initially defined in glioblastoma cells after ectopic expression of activated Ras, but recent reports have described small molecules that can induce the features of methuosis in a broad spectrum of cancer cells, including those that are resistant to conventional apoptosis-inducing drugs. This review summarizes the available information about the distinguishing morphological characteristics and underlying mechanisms of methuosis. We compare and contrast methuosis with other cytopathological conditions in which accumulation of clear cytoplasmic vacuoles is a prominent feature. Finally, we highlight key questions that need to be answered to determine whether methuosis truly represents a unique form of regulated cell death. PMID:24726643

Uncommon Localization of Extrarenal Xp11.2 Translocation-associated Renal Cell Carcinoma (RCC): Case Report.

PubMed

Al-Maghrabi, Jaudah Ahmed; Khabaz, Mohamad Nidal

2017-09-04

The World Health Organization has recognized Xp11.2 translocation-associated renal cell carcinoma (RCC) as a distinct neoplasm that arises within the kidney. Although many reports of extrarenal carcinoma may be found in the literature, to the best of our knowledge, Xp11 translocation-associated RCC with intact kidneys has not been documented. This report describes a multilobulated right retroperitoneal soft tissue mass (7.9×5.3×12.6 cm) of a 37-year-old man complaining of abdominal pain in the right side. The patient underwent a computed tomography-guided biopsy. Microscopic evaluation reveals a tumor with papillary and sheaths architectures with cells revealing clear to eosinophilic cytoplasm. Immunohistochemical evaluation on the biopsy reveals that the tumor is positive for PAX-8, CD10, and TFE3. It is negative for CK7, EMA, Vimentin, RCC, CK8/18, D20, CD3, PLAP, OCT4, CD30, MART-1, Inhibin, S-100, HMB-45, Desmin, SMA, and DOG-1. The diagnosis was malignant epithelioid neoplasm and the diagnosis of translocation RCC was suggested. Excision was recommended. The patient underwent right radical nephrectomy with removal of this large mass. Pathologic examination showed a large cystic and solid, nonhomogenous mass with some necrotic areas, originating from the perirenal fat between the adrenal gland and the kidney. Microscopic features showed a tumor with papillary, rhabdoid, and clear cell features. Immunohistochemical stains showed that the tumor cells positively expressed AMACR, PAX-8, CD10, RCC, and TFE3, but were negative for cytokeratins, vimentin, HMB-45, desmin, SMA, EMA, and MSA. Cytogenetic studies confirmed the diagnosis of Xp11.2 translocation-associated RCC with positive TFE3 gene rearrangement. To the best of our knowledge, this type of extrarenal tumor has never been reported.

SFRP1 is a possible candidate for epigenetic therapy in non-small cell lung cancer.

PubMed

Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki

2016-08-12

Non-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments. Recent studies have indicated that epigenetic therapy, which targets epigenetic effects, might be a new therapeutic methodology for NSCLC. However, it is not clear which objects (e.g., genes) this treatment specifically targets. Secreted frizzled-related proteins (SFRPs) are promising candidates for epigenetic therapy in many cancers, but there have been no reports of SFRPs targeted by epigenetic therapy for NSCLC. This study performed a meta-analysis of reprogrammed NSCLC cell lines instead of the direct examination of epigenetic therapy treatment to identify epigenetic therapy targets. In addition, mRNA expression/promoter methylation profiles were processed by recently proposed principal component analysis based unsupervised feature extraction and categorical regression analysis based feature extraction. The Wnt/β-catenin signalling pathway was extensively enriched among 32 genes identified by feature extraction. Among the genes identified, SFRP1 was specifically indicated to target β-catenin, and thus might be targeted by epigenetic therapy in NSCLC cell lines. A histone deacetylase inhibitor might reactivate SFRP1 based upon the re-analysis of a public domain data set. Numerical computation validated the binding of SFRP1 to WNT1 to suppress Wnt signalling pathway activation in NSCLC. The meta-analysis of reprogrammed NSCLC cell lines identified SFRP1 as a promising target of epigenetic therapy for NSCLC.

SHBG Is an Important Factor in Stemness Induction of Cells by DHT In Vitro and Associated with Poor Clinical Features of Prostate Carcinomas

PubMed Central

Ma, Yuanyuan; Liang, Dongming; Liu, Jian; Wen, Jian-Guo; Servoll, Einar; Waaler, Gudmund; Sæter, Thorstein; Axcrona, Karol; Vlatkovic, Ljiljana; Axcrona, Ulrika; Paus, Elisabeth; Yang, Yue; Zhang, Zhiqian; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

2013-01-01

Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog. Moreover, sex hormone binding globulin (SHBG) was also simultaneously upregulated in these cells. When the SHBG gene was blocked by SHBG siRNA knock-down, the induction of Oct3/4, Nanog, CD44 and CD90 by DHT was also correspondingly blocked in these cells. Immunohistochemical evaluation of clinical samples disclosed weakly positive, and areas negative for SHBG expression in the benign prostate tissues, while most of the prostate carcinomas were strongly positive for SHBG. In addition, higher levels of SHBG expression were significantly associated with higher Gleason score, more seminal vesicle invasions and lymph node metastases. Collectively, our results show a role of SHBG in upregulating stemness of prostate cancer cells upon DHT exposure in vitro, and SHBG expression in prostate cancer samples is significantly associated with poor clinicopathological features, indicating a role of SHBG in prostate cancer progression. PMID:23936228

Pancreatic mixed serous neuroendocrine neoplasm with clear cells leading to diagnosis of von Hippel Lindau disease.

PubMed

Kakkar, Aanchal; Sharma, Mehar C; Yadav, Rajni; Panwar, Rajesh; Mathur, Sandeep R; Iyer, Venkateswaran K; Sahni, Peush

2016-08-01

Mixed serous neuroendocrine neoplasms are extremely rare tumors that are usually seen in female patients and are often associated with von Hippel Lindau (VHL) disease. We describe the case of a 38-year-old male who presented with complaints of anorexia, weight loss, and abdominal pain. CT abdomen showed a mass in the head of the pancreas, multiple small nodules in the body of pancreas, and bilateral adrenal masses. Fine needle aspiration cytology (FNAC) from the mass showed features of a neuroendocrine tumor, with many of the cells demonstrating abundant clear cytoplasm. Histopathological examination of the pancreaticoduodenectomy specimen showed a mixed serous neuroendocrine neoplasm with two components viz. serous cystadenoma and neuroendocrine tumor (NET) World Health Organization (WHO) grade 2. In addition, he was diagnosed to have bilateral pheochromocytomas and a paraganglioma. The synchronicity of these tumors suggested the possibility of VHL disease. Thus, identification of a NET with clear cells or of a mixed serous neuroendocrine neoplasm should raise suspicion of VHL disease. In a mixed tumor, FNAC may identify only one of the two components. Thorough processing of all pancreatic serous tumors for pathological examination is recommended, as NET may occur as a small nodule within the serous cystadenoma. Copyright © 2016 Elsevier GmbH. All rights reserved.

Beyond the frontiers of neuronal types

PubMed Central

Battaglia, Demian; Karagiannis, Anastassios; Gallopin, Thierry; Gutch, Harold W.; Cauli, Bruno

2012-01-01

Cortical neurons and, particularly, inhibitory interneurons display a large diversity of morphological, synaptic, electrophysiological, and molecular properties, as well as diverse embryonic origins. Various authors have proposed alternative classification schemes that rely on the concomitant observation of several multimodal features. However, a broad variability is generally observed even among cells that are grouped into a same class. Furthermore, the attribution of specific neurons to a single defined class is often difficult, because individual properties vary in a highly graded fashion, suggestive of continua of features between types. Going beyond the description of representative traits of distinct classes, we focus here on the analysis of atypical cells. We introduce a novel paradigm for neuronal type classification, assuming explicitly the existence of a structured continuum of diversity. Our approach, grounded on the theory of fuzzy sets, identifies a small optimal number of model archetypes. At the same time, it quantifies the degree of similarity between these archetypes and each considered neuron. This allows highlighting archetypal cells, which bear a clear similarity to a single model archetype, and edge cells, which manifest a convergence of traits from multiple archetypes. PMID:23403725

Elucidating encounters of atypical ductal hyperplasia arising in gynaecomastia.

PubMed

Wells, Justin M; Liu, Yifang; Ginter, Paula S; Nguyen, Michaela T; Shin, Sandra J

2015-02-01

Atypical ductal hyperplasia (ADH) rarely arises in gynaecomastia. We set out to understand more clearly the clinical, histological and immunohistochemical features of ADH in this setting. Twenty-five cases of ADH arising in gynaecomastia, nine cases of ductal carcinoma in situ (DCIS) and 36 cases of gynaecomastia with usual ductal hyperplasia (UDH) were studied. Reviews of clinical, morphological and immunohistochemical findings were performed. The extent of cytokeratin 5/6 (CK5/6) luminal epithelial cell staining was assessed (0% = 0, < 10% = 1, 10-50% = 2 and > 50% = 3). Oestrogen receptor (ER) was evaluated using the H-scoring system. The average age of ADH patients was 35 years (range 14-78). ADH was bilateral in 20% and less frequent in active gynaecomastia (24%). ADH often showed a cribriform pattern (72%), with less nuclear variation/size and similar frequency of mitoses than UDH cells. CK5/6 luminal epithelial staining was decreased in ADH (68%) versus UDH (11%). ADH showed high ER expression compared to UDH (H score > 270 in 88% and 14%, respectively). ADH in gynaecomastia can be distinguished from UDH by morphological and immunohistochemical features. We also identified a subset of young patients (< 25 years) with extensive bilateral ADH. More studies are needed to characterize this patient subset more clearly. © 2014 John Wiley & Sons Ltd.

Diagnostic pitfall on the histological spectrum of adult-onset renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

PubMed

Kuroda, Naoto; Katto, Kazunobu; Tanaka, Yukichi; Yamaguchi, Tadanori; Inoue, Kaori; Ohara, Masahiko; Mizuno, Keiko; Hes, Ondrej; Michal, Michal; Lee, Gang-Hong

2010-06-01

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion recently has been found. In this article, we demonstrate an unusual features of such a case. A 73-year-old Japanese woman presented with macroscopic hematuria. The imaging examinations disclosed the renal tumor. Histological examination showed the finding of ASPL-TFE3 RCC, which was characterized by papillary, alveolar, or solid growth of voluminous cell with clear and eosinophilic cells, and stromal psammoma body and hyaline nodules. Additionally, shrunken nuclei, thick cell border, and perinuclear clearing characteristic of chromophobe renal cell carcinoma were observed in the alveolar growth area and the transitional zone between stromal hyalinization, and osseous metaplasia was identified. Immunohistochemically, nuclei of tumorous cell were diffusely positive for TFE3. A RT-PCR study revealed the ASPL-TFE3 chimeric transcript. Finally, pathologists should recognize that the histology of RCC associated with Xp11.2 translocation/TFE3 gene fusion may focally resemble that of chromophobe RCC, but TFE3 immunohistochemistry and molecular genetic study may be helpful in the differential diagnosis. Moreover, osseous metaplasia as well as psammoma bodies should be added to the histological spectrum of the stromal change in RCC associated with Xp11.2 translocations/TFE3 gene fusions.

Influence of salinomycin treatment on division and movement of individual cancer cells cultured in normoxia or hypoxia evaluated with time-lapse digital holographic microscopy

PubMed Central

Kamlund, Sofia; Strand, Daniel; Janicke, Birgit; Alm, Kersti; Oredsson, Stina

2017-01-01

ABSTRACT Most studies on new cancer drugs are based on population-derived data, where the absence of response of a small population may pass unnoticed. Thus, individual longitudinal tracking of cells is important for the future development of efficient cancer treatments. We have used digital holographic microscopy to track individual JIMT-1 human breast cancer cells and L929 mouse fibroblast cultivated in normoxia or hypoxia. In addition, JIMT-1 cells were treated with salinomycin, a cancer stem cell targeting compound. Three-day time-lapse movies were captured and individual cells were analysed with respect to cell division (cell cycle length) and cell movement. Comparing population-doubling time derived from population-based growth curves and individual cell cycle time data from time-lapse movies show that the former hide a sub-population of dividing cells. Salinomycin treatment increased the motility of cells, however, this motility did not result in an increased distant migration i.e. the cells increased their local movement. MCF-7 breast cancer cells showed similar motility behaviour as salinomycin-treated JIMT-1 cells. We suggest that combining features, such as motility and migration, can be used to distinguish cancer cells with mesenchymal (JIMT-1) and epithelial (MCF-7) features. The data clearly emphasize the importance of longitudinal cell tracking to understand the biology of individual cells under different conditions. PMID:28933990

Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

NASA Astrophysics Data System (ADS)

Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

2014-03-01

Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

Angiomyolipoma with Minimal Fat: Can It Be Differentiated from Clear Cell Renal Cell Carcinoma by Using Standard MR Techniques?

PubMed Central

Hindman, Nicole; Ngo, Long; Genega, Elizabeth M.; Melamed, Jonathan; Wei, Jesse; Braza, Julia M.; Rofsky, Neil M.

2012-01-01

Purpose: To retrospectively assess whether magnetic resonance (MR) imaging with opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses. Materials and Methods: Institutional review board approval and a waiver of informed consent were obtained for this HIPAA-compliant study. MR images from 108 pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs from 64 men and 44 women) at two academic institutions were evaluated. The signal intensity (SI) of each renal mass and spleen on opposed-phase and in-phase GRE images was used to calculate an SI index and tumor-to-spleen SI ratio. Two radiologists who were blinded to the pathologic results independently assessed the subjective presence of intravoxel fat (ie, decreased SI on opposed-phase images compared with that on in-phase images), SI on T1-weighted and T2-weighted images, cystic degeneration, necrosis, hemorrhage, retroperitoneal collaterals, and renal vein thrombosis. Results were analyzed by using the Wilcoxon rank sum test, two-tailed Fisher exact test, and multivariate logistic regression analysis for all renal masses and for small masses. A P value of less than .05 was considered to indicate a statistically significant difference. Results: There were no differences between minimal fat AMLs and clear cell RCCs for the SI index (8.05% ± 14.46 vs 14.99% ± 19.9; P = .146) or tumor-to-spleen ratio (−8.96% ± 16.6 and −15.8% ± 22.4; P = .227) when all masses or small masses were analyzed. Diagnostic accuracy (area under receiver operating characteristic curve) for the SI index and tumor-to-spleen ratio was 0.59. Intratumoral necrosis and larger size were predictive of clear cell RCC (P < .001) for all lesions, whereas low SI (relative to renal parenchyma SI) on T2-weighted images, smaller size, and female sex correlated with minimal fat AML (P < .001) for all lesions. Conclusion: The diagnostic accuracy of opposed-phase and in-phase GRE MR imaging for the differentiation of minimal fat AML and clear cell RCC is poor. In this cohort, low SI on T2-weighted images relative to renal parenchyma and small size suggested minimal fat AML, whereas intratumoral necrosis and large size argued against this diagnosis. © RSNA, 2012 PMID:23012463

Juxtaglomerular cell tumor of the kidney: report of two cases with a papillary pattern.

PubMed

Têtu, B; Vaillancourt, L; Camilleri, J P; Bruneval, P; Bernier, L; Tourigny, R

1993-11-01

We report the clinicopathologic, immunohistochemical, and electron microscopic study of two cases of juxtaglomerular cell tumor of the kidney with a hitherto unreported dominant papillary pattern. Both tumors were associated with high blood pressure that did not respond to medical therapy, but that returned to normal after removal of the kidney. They were well delineated, tan, and had no necrosis. The cores of the papillary structures consisted of polygonal cells found to express renin by immunohistochemistry and to contain renin protogranules by electron microscopy. The papillary fronds were covered by one layer of cuboidal epithelial cells that did not stain for renin and had ultrastructural features reminiscent of the collecting duct epithelium. These tumors must be differentiated from malignant papillary tumors of the kidney, such as papillary clear cell carcinoma, transitional cell carcinoma, and collecting duct carcinoma.

Label-free and live cell imaging by interferometric scattering microscopy.

PubMed

Park, Jin-Sung; Lee, Il-Buem; Moon, Hyeon-Min; Joo, Jong-Hyeon; Kim, Kyoung-Hoon; Hong, Seok-Cheol; Cho, Minhaeng

2018-03-14

Despite recent remarkable advances in microscopic techniques, it still remains very challenging to directly observe the complex structure of cytoplasmic organelles in live cells without a fluorescent label. Here we report label-free and live-cell imaging of mammalian cell, Escherischia coli , and yeast, using interferometric scattering microscopy, which reveals the underlying structures of a variety of cytoplasmic organelles as well as the underside structure of the cells. The contact areas of the cells attached onto a glass substrate, e.g. , focal adhesions and filopodia, are clearly discernible. We also found a variety of fringe-like features in the cytoplasmic area, which may reflect the folded structures of cytoplasmic organelles. We thus anticipate that the label-free interferometric scattering microscopy can be used as a powerful tool to shed interferometric light on in vivo structures and dynamics of various intracellular phenomena.

Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression.

PubMed

Brooks, Samira A; Khandani, Amir H; Fielding, Julia R; Lin, Weili; Sills, Tiffany; Lee, Yueh; Arreola, Alexandra; Milowsky, Mathew I; Wallen, Eric M; Woods, Michael E; Smith, Angie B; Nielsen, Mathew E; Parker, Joel S; Lalush, David S; Rathmell, W Kimryn

2016-06-15

Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans. ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis. Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype. Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Histotype-genotype correlation in 36 high-grade endometrial carcinomas.

PubMed

Hoang, Lien N; McConechy, Melissa K; Köbel, Martin; Han, Guangming; Rouzbahman, Marjan; Davidson, Ben; Irving, Julie; Ali, Rola H; Leung, Sam; McAlpine, Jessica N; Oliva, Esther; Nucci, Marisa R; Soslow, Robert A; Huntsman, David G; Gilks, C Blake; Lee, Cheng-Han

2013-09-01

Endometrioid, serous, and clear cell carcinomas are the major types of endometrial carcinoma. Histologic distinction between these different tumor types can be difficult in high-grade cases, in which significant interobserver diagnostic disagreement exists. Endometrioid and clear cell carcinomas frequently harbor ARID1A and/or PTEN mutations. Serous carcinoma acquires TP53 mutations/inactivation at onset, with a significant subset harboring an additional mutation in PPP2R1A. This study examines the correlation between tumor histotype and genotype in 36 previously genotyped high-grade endometrial carcinomas. This included 23 endometrioid/clear cell genotype and 13 serous genotype tumors. Eight subspecialty pathologists reviewed representative online slides and rendered diagnoses before and after receiving p53, p16, and estrogen receptor immunostaining results. κ statistics for histotype-genotype concordance were calculated. The average κ values for histotype-genotype concordance was 0.55 (range, 0.30 to 0.67) on the basis of morphologic evaluation alone and it improved to 0.68 (range, 0.54 to 0.81) after immunophenotype consideration (P<0.001). Genotype-incompatible diagnoses were rendered by at least 2 pathologists in 12 of 36 cases (33%) (3 cases by 2/8 pathologists, 2 by 3/8, 2 by 4/8, 3 by 6/8, 1 by 7/8, and 1 case by 8/8 pathologists). Six of the 12 were endometrioid/clear cell genotype tumors, and the other 6 were serous genotype tumors. The histopathologic features associated with histotype-genotype-discordant cases were reviewed, and specific diagnostic recommendations were made to improve concordance. This study found that although the majority of morphologic diagnoses are genotype concordant, genotype-incompatible diagnoses are made in a significant subset of cases. Judicious use and interpretation of p53 immunohistochemistry in selected scenarios can improve histotype-genotype concordance.

Familial Non-VHL Clear Cell Renal Cell Carcinoma

MedlinePlus

... Cell Carcinoma Request Permissions Familial Non-VHL Clear Cell Renal Cell Carcinoma Approved by the Cancer.Net Editorial Board , 12/2017 What is familial non-VHL clear cell renal cell carcinoma? Familial non-VHL clear cell ...

[Case report of rare co-occurrence of renal cell carcinoma and crossed renal dystopia (L-shaped kidney)].

PubMed

Bakov, V N; Los, M S

2017-10-01

L-shaped kidney refers to a rare anomaly of the relative kidney positioning. Due to low prevalence, the literature on the co-occurrence of this anomaly with malignancy is lacking. And, if the diagnosis of a renal anomaly does not present difficulties, if a tumor is detected in such a kidney, even MSCT does not always help differentiate a pelvic tumor from a tumor of the renal parenchyma spreading to the pelvicalyceal system. This has important implications for choosing an appropriate surgical strategy. A feature of the presented clinical observation is the co-occurrence of the rare anomaly of kidney position and locally advanced renal cell carcinoma spreading to the renal pelvis. Due to the massive spread of the tumor, an organ-sparing surgery was not feasible. Due to the suspicion of tumor spread to the renal pelvis, the patient underwent nephrureterectomy of the L-shaped kidney. Introduction to renoprival state with transfer to chronic hemodialysis became the only option to maintain homeostasis and extend the patients life. Histological examination revealed clear cell renal cell carcinoma with invasion of the pelvis and renal capsule, with no clear demarcation between the fused kidneys.

Simultaneous targeted activation of Notch1 and Vhl-disruption in the kidney proximal epithelial tubular cells in mice

PubMed Central

Johansson, Elinn; Rönö, Birgitte; Johansson, Martin; Lindgren, David; Möller, Christina; Axelson, Håkan; Smith, Emma M. K.

2016-01-01

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, representing approximately 75% of all renal neoplasms. ccRCC is known to be strongly associated with silencing of the von Hippel Lindau (VHL) tumor suppressor gene, yet VHL deficiency alone does not seem to be sufficient to drive the oncogenic transformation of normal renal epithelium and induce renal tumorigenesis. We, and others, have previously suggested that constitutive activation of the Notch signaling pathway, alongside with VHL loss, contribute to the oncogenic features of ccRCC. Here we report a prevailing hyperactivation of the Notch1 receptor in human ccRCC relative to the healthy counterpart. To explore the consequences of the elevated Notch1 signaling observed in ccRCC patient material, we made use of a conditional mouse model based on concurrent ectopic expression of constitutively active Notch1 (NICD1) and deletion of the Vhl gene. Histological examination of the kidneys of the conditional mice demonstrate the existence of nests of dysplastic cells with a clear cytoplasm as a consequence of lipid accumulation, thus displaying a one important hallmark of human ccRCC. PMID:27491826

Clinical and Pathologic Study of Feline Merkel Cell Carcinoma With Immunohistochemical Characterization of Normal and Neoplastic Merkel Cells.

PubMed

Dohata, A; Chambers, J K; Uchida, K; Nakazono, S; Kinoshita, Y; Nibe, K; Nakayama, H

2015-11-01

The authors herein describe the morphologic and immunohistochemical features of normal Merkel cells as well as the clinicopathologic findings of Merkel cell carcinoma in cats. Merkel cells were characterized as vacuolated clear cells and were individually located in the epidermal basal layer of all regions examined. Clusters of Merkel cells were often observed adjacent to the sinus hair of the face and carpus. Immunohistochemically, Merkel cells were positive for cytokeratin (CK) 20, CK18, p63, neuron-specific enolase, synaptophysin, and protein gene product 9.5. Merkel cell carcinoma was detected as a solitary cutaneous mass in 3 aged cats (13 to 16 years old). On cytology, large lymphocyte-like cells were observed in all cases. Histologic examinations of surgically resected tumors revealed nests of round cells separated by various amounts of a fibrous stroma. Tumor cells were commonly immunopositive for CK20, CK18, p63, neuron-specific enolase, and synaptophysin, representing the characteristics of normal Merkel cells. © The Author(s) 2015.

Single-cell MALDI-MS as an analytical tool for studying intrapopulation metabolic heterogeneity of unicellular organisms.

PubMed

Amantonico, Andrea; Urban, Pawel L; Fagerer, Stephan R; Balabin, Roman M; Zenobi, Renato

2010-09-01

Heterogeneity is a characteristic feature of all populations of living organisms. Here we make an attempt to validate a single-cell mass spectrometric method for detection of changes in metabolite levels occurring in populations of unicellular organisms. Selected metabolites involved in central metabolism (ADP, ATP, GTP, and UDP-Glucose) could readily be detected in single cells of Closterium acerosum by means of negative-mode matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The analytical capabilities of this approach were characterized using standard compounds. The method was then used to study populations of individual cells with different levels of the chosen metabolites. With principal component analysis and support vector machine algorithms, it was possible to achieve a clear separation of individual C. acerosum cells in different metabolic states. This study demonstrates the suitability of mass spectrometric analysis of metabolites in single cells to measure cell-population heterogeneity.

A dual-emission and large Stokes shift fluorescence probe for real-time discrimination of ROS/RNS and imaging in live cells.

PubMed

Guo, Ting; Cui, Lei; Shen, Jiaoning; Wang, Rui; Zhu, Weiping; Xu, Yufang; Qian, Xuhong

2013-03-04

A novel dual-emission fluorescence probe has been developed for specific and sensitive detection of hypochlorite (ClO(-)). Upon addition of ClO(-), significant changes in fluorescence emission intensity at two discrete wavelengths were observed. Meanwhile OONO(-) led to only a single-channel fluorescence enhancement. This feature makes it a clear advantage in distinguishing ClO(-), RNS from other ROS.

[Clinicopathologic study of sinonasal teratocarcinosarcoma and its contrast with olfactory neuroblastoma].

PubMed

Li, Xue; Liu, Hong-Gang; Xie, Xin-Ji; Han, Yi-Ding; Li, Ming

2008-07-01

To study the clinicopathologic features, diagnosis and differential diagnosis of sinonasal teratocarcinosarcoma (SNTCS) and olfactory neuroblastoma (ONB), and to discuss the histogenesis and possible relationship between SNTCS and ONB. Seven cases of SNTCS and 34 cases of ONB were retrieved from the pathological archives together with one case each of malignant teratoma and immature embryonic tissue at 8 weeks were collected from Beijing Tongren Hospital. The clinicopathologic features were analyzed and immunohistochemical staining was performed on paraffin sections. Six of the SNTCS patients were male and one was female. The patients age range was 25 to 69 years (mean age 46). Four cases were initial presentation and three were recurrences. Histologically, the tumor shows multiple tissue components derived from three germ layers. There were mixture of teratoma-like tissue and carcinosarcoma. The components include fetal clear cell squamous epithelium derived from ectoderm. Glandular and tubular structures and ciliated columnar epithelium derived from endoderm. Fibroblasts, striated muscle, smooth muscle, cartilage and osteoid matrix derived from mesoderm. The carcinoma component exhibited mostly adenocarcinoma and squamous cell carcinoma, whereas the sarcoma component mostly exhibited rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In addition, carcinoid, and primitive mesenchymal tissue and the ONB component were also seen. The morphological characteristics of SNTCS comprised fetal clear cell squamous epithelium, carcinosarcoma and the ONB component. By immunohistochemistry, the epithelial component and cells with epithelium differentiation were positive for cytokeratin (pan) and EMA. The ONB component was positive for Syn, NSE, CD99, NF and CgA to different degrees. Neurofibril bundles were positive for S-100, and Flexner-Wintersteiner rosettes expressed cytokeratin (pan) and EMA. The spindle cells expressed vimentin, SMA, desmin, myosin and myoglobin. The primitive mesenchymal tissue expressed vimentin, and the mucoid materials and glycogen were positive for PAS. GFAP was negative in all cases. The 34 cases of ONB, included 18 men and 16 women, the age ranged from 12 to 72 years (mean 42.8 years). Microscopically, the tumor shows epithelial nests, net of angioma-like fibrous connective tissues, small round and spindle cells, glandular, squamous-like cells, and cells of rhabdomyoblastic differentiation, Homer-Wright and Flexner rosette, bundles of neurofibrils, etc. NSE and CgA were expressed in small cells. S-100 protein was positive in the areas of bunches of neurofibril. Cytokeratin (pan) was positive in epithelial cells. Myoglobin was positive in the cells of rhabdomyoblastic differentiation. The single case of immature malignant teratoma exhibited primitive nerve tissue, but fetal clear cell squamous epithelium was not found. In the immature embryonic tissue, rudimentary organs were formed, with fetal clear cell squamous epithelium lining present on the nasal and oral cavities surface. SNTCS is a rare and aggressive malignant neoplasm. Most of ONB are low-grade malignant tumors. Morphological differences are the most important basis to make differentiate SNTCS from ONB. As SNTCS may demonstrate a multiplicity of structures and pleomorphism, inadequate sampling at biopsy, therefore, may lead to errors in diagnosis. No evidence show that SNTCS are derived from germ cells and sinonasal teratoid carcinosarcoma may be a more proper name. SNTCS probably arises from primitive totipotential cells of olfactory/sinonasal membrane, and the relationship between SNTCS and ONB needs further study.

Clear cell renal cell carcinoma: validation of World Health Organization/International Society of Urological Pathology grading.

PubMed

Dagher, Julien; Delahunt, Brett; Rioux-Leclercq, Nathalie; Egevad, Lars; Srigley, John R; Coughlin, Geoffrey; Dunglinson, Nigel; Gianduzzo, Troy; Kua, Boon; Malone, Greg; Martin, Ben; Preston, John; Pokorny, Morgan; Wood, Simon; Yaxley, John; Samaratunga, Hemamali

2017-12-01

In 2012, the International Society of Urological Pathology (ISUP) introduced a novel grading system for clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma. This system is incorporated into the latest World Health Organization renal tumour classification, being designated WHO/ISUP grading. This study was undertaken to compare WHO/ISUP and Fuhrman grading and to validate WHO/ISUP grading as a prognostic parameter in a series of clear cell RCC. Analysis of 681 cases of ccRCC showed that 144 tumours could not be assigned a Fuhrman grade on the basis of ambiguous grading features. The application of WHO/ISUP grading resulted in a general down-grading of cases when compared with Fuhrman grading. In a sub-group of 374 cases, for which outcome data were available, 9.3% were WHO/ISUP grade 1, 50.3% were grade 2, 24.1% grade 3 and 16.3% grade 4, while the distribution of Fuhrman grades was 0.4% grade 1, 48.7% grade 2, 29.4% grade 3 and 21.5% grade 4. There were no recurrence/metastases amongst patients with WHO/ISUP grade 1 tumours and there was a significant difference in outcome for WHO/ISUP grades 2, 3 and 4. For Fuhrman grading the cancer-free survival was not significantly different for grade 2 and grade 3 tumours. On multivariate analysis WHO/ISUP grade and pT staging category were found to retain prognostic significance. The study demonstrates that FG cannot be applied in >20% of cases of ccRCC and the WHO/ISUP provides superior prognostic information. © 2017 John Wiley & Sons Ltd.

Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer.

PubMed

Ramalingam, Preetha

2016-02-01

Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical markers are routinely employed in the diagnosis of epithelial ovarian carcinomas. However, molecular testing of these tumors, unlike in endometrial carcinoma, is not routinely used in clinical practice.

Morphology and ultrastructure of the adrenal gland in Bactrian camels (Camelus bactrianus).

PubMed

Ye, Wen-Ling; Wang, Feng-Ling; Wang, Hong-Ju; Wang, Jian-Lin

2017-04-01

In the present study, we examined the morphological features of the adrenal gland in Bactrian camel by means of digital anatomy, light and electron microscopy. Our findings testified that the gland was divided into three parts, capsule, cortex and medulla from outside to inside as other mammals, and the cortex itself was further distinguished into four zones: zona glomerulosa, zona intermedia, zona fasciculate and zona reticularis. Notably, the zona intermedia could be seen clearly in the glands from females and castrated males, whereas it was not morphologically clear in male. There was a great deal of lipid droplets in the zona fasciculate, while it was fewer in the zona glomerulosa and zona reticularis. The cytoplasm of adrenocortical cell contained rich mitochondria and endoplasmic reticulum. The adrenal medulla was well-developed with two separations of external and internal zones. The most obvious histological property of adrenal medulla cells were that they contained a huge number of electron-dense granules enveloped by the membrane, and so medulla cells could be divided into norepinephrine cells and epinephrine cells. Moreover, the cortical cuffs were frequently present in adrenal gland. Results of this study provides a theoretical basis necessary for ongoing investigations on Bactrian camels and their good adaptability in arid and semi-arid circumstances. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perivascular Epithelioid Cell Tumor of Gastrointestinal Tract

PubMed Central

Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Kuiper, Roland P.; Song, Minmin; Zhang, Xiaoli; Song, Shunxin; van Kessel, Ad Geurts; Iwamoto, Aikichi; Wang, Jianping; Liu, Huanliang

2015-01-01

Perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas) are exceedingly rare, with only a limited number of published reports worldwide. Given the scarcity of GI PEComas and their relatively short follow-up periods, our current knowledge of their biologic behavior, molecular genetic alterations, diagnostic criteria, and prognostic factors continues to be very limited. We present 2 cases of GI PEComas, one of which showed an aggressive histologic behavior that underwent multiple combined chemotherapies. We also review the available English-language medical literature on GI PEComas-not otherwise specified (PEComas-NOS) and discuss their clinicopathological and molecular genetic features. Pathologic analyses including histomorphologic, immunohistochemical, and ultrastructural studies were performed to evaluate the clinicopathological features of GI PEComas, their diagnosis, and differential diagnosis. Immunohistochemistry, semiquantitative reverse transcriptase polymerase chain reaction, and DNA sequencing assays were carried out to detect the potential molecular genetic alterations in our cases Microscopically, the tumors showed distinctive histologic features of PEComas-NOS, including fascicular or nested architecture, epithelioid or spindled cell type, and clear to eosinophilic cytoplasm. The tumor cells were immunohistochemically positive for melanocytic markers. Molecular pathological assays confirmed a PSF-TFE3 gene fusion in one of our cases. Furthermore, in this case microphthalmia-associated transcription factor and its downstream genes were found to exhibit elevated transcript levels. Knowledge about the molecular genetic alterations in GI PEComas is still limited and warrants further study. PMID:25621681

Clinicopathological findings of primary esophageal malignant melanoma: report of six cases and review of literature.

PubMed

Zheng, Jinfeng; Mo, Haiying; Ma, Shufang; Wang, Zhenzheng

2014-01-01

We studied images and histopathological features of primary esophageal malignant melanoma to explore the clinical pathological features, diagnosis, differential diagnoses, and treatment. Immunolabelling was conducted on six cases of esophageal malignant melanoma using histological and immunohistochemical techniques. Combined with the related literature, the clinical manifestations, imaging, histopathological and immunohistochemical features, treatment, and prognosis of primary esophageal malignant melanoma were observed and analyzed. The six patients with primary esophageal malignant melanoma were all male with an average age of 63.4 years. Poor food intake was observed in all patients, and the symptoms showed progressive aggravation. Endoscopic feed tube revealed dark brown and black nodular and polypoid lesions, 1/4-1/2 loop cavity. Tumor histopathology revealed the following characteristics: tumor cells arranged in nests, sheets and cords, round or polygonal, abundant and red-stained cytoplasm, melanin granules in the cytoplasm, heterogeneous nucleus sizes, centered or deviated nuclei, clearly identifiable nucleoli, and apparent pathological mitosis. The immune phenotype was as follows: tumor cells had diffuse expression of HMB45, Melan A, and S100. The cells were CK negative, and the Ki67-positive cell number was 40%-45%. Primary esophageal malignant melanoma is rare with high malignancy and poor prognosis. Immunohistochemical staining is helpful for diagnosing this tumor. The differential diagnosis includes low differentiated carcinoma, primitive neuroectodermal tumor, esophageal sarcomatoid carcinoma, esophageal lymphoma, and other tumors.

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.

PubMed

Huang, Hsien-Neng; Chiang, Ying-Cheng; Cheng, Wen-Fang; Chen, Chi-An; Lin, Ming-Chieh; Kuo, Kuan-Ting

2015-02-01

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P<0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age >45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.

The Impact of parasitic loss on solar cells with plasmonic nano-textured rear reflectors.

PubMed

Disney, Claire E R; Pillai, Supriya; Green, Martin A

2017-10-09

Significant photocurrent enhancement has been demonstrated using plasmonic light-trapping structures comprising nanostructured metallic features at the rear of the cell. These structures have conversely been identified as suffering heightened parasitic absorption into the metal at certain resonant wavelengths severely mitigating benefits of light trapping. In this study, we undertook simulations exploring the relationship between enhanced absorption into the solar cell, and parasitic losses in the metal. These simulations reveal that resonant wavelengths associated with high parasitic losses in the metal could also be associated with high absorption enhancement in the solar cell. We identify mechanisms linking these parasitic losses and absorption enhancements, but found that by ensuring correct design, the light trapping structures will have a positive impact on the overall solar cell performance. Our results clearly show that the large angle scattering provided by the plasmonic nanostructures is the reason for the enhanced absorption observed in the solar cells.

Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing.

PubMed

Gao, Shuai; Yan, Liying; Wang, Rui; Li, Jingyun; Yong, Jun; Zhou, Xin; Wei, Yuan; Wu, Xinglong; Wang, Xiaoye; Fan, Xiaoying; Yan, Jie; Zhi, Xu; Gao, Yun; Guo, Hongshan; Jin, Xiao; Wang, Wendong; Mao, Yunuo; Wang, Fengchao; Wen, Lu; Fu, Wei; Ge, Hao; Qiao, Jie; Tang, Fuchou

2018-06-01

The development of the digestive tract is critical for proper food digestion and nutrient absorption. Here, we analyse the main organs of the digestive tract, including the oesophagus, stomach, small intestine and large intestine, from human embryos between 6 and 25 weeks of gestation as well as the large intestine from adults using single-cell RNA-seq analyses. In total, 5,227 individual cells are analysed and 40 cell types clearly identified. Their crucial biological features, including developmental processes, signalling pathways, cell cycle, nutrient digestion and absorption metabolism, and transcription factor networks, are systematically revealed. Moreover, the differentiation and maturation processes of the large intestine are thoroughly investigated by comparing the corresponding transcriptome profiles between embryonic and adult stages. Our work offers a rich resource for investigating the gene regulation networks of the human fetal digestive tract and adult large intestine at single-cell resolution.

Adenoid basal cell carcinoma: a rare facet of basal cell carcinoma

PubMed Central

Saxena, Kartikay; Manohar, Vidya; Bhakhar, Vikas; Bahl, Sumit

2016-01-01

Basal cell carcinoma (BCC) is a common, locally invasive epithelial malignancy of skin and its appendages. Every year, close to 10 million people get diagnosed with BCC worldwide. While the histology of this lesion is mostly predictable, some of the rare histological variants such as cystic, adenoid, morpheaform, infundibulocystic, pigmented and miscellaneous variants (clear-cell, signet ring cell, granular, giant cell, adamantanoid, schwannoid) are even rarer, accounting for <10% of all BCC's. Adenoid BCC (ADBCC) is a very rare histopathological variant with reported incidence of only approximately 1.3%. The clinical appearance of this lesion can be a pigmented or non-pigmented nodule or ulcer without predilection for any particular site. We share a case report of ADBCC, a rare histological variant of BCC that showed interesting features not only histologically but also by clinically mimicking a benign lesion. PMID:27095806

Limbal explants from cryopreserved cadaver human corneas. Immunofluorescence and light microscopy of epithelial cells growing in culture.

PubMed

Bratanov, M; Neronov, A; Nikolova, E

2009-01-01

The aim of the present study was to determine whether human cadaver corneas, that were subject to cryopreservation, would be a source of migrating epithelial cells in vitro and what kind of morphological features these cells possess. Limbal explant culture was used for expanding the epithelial cells. Non-quantitative light microscopical examinations of the cultures within a period of 28 days were carried out. The phenotype of cultured cells, particularly of the presumed adult stem cell population, was examined by indirect fluorescent immunostaining using antibodies against corneal stem cell associated markers p63 and vimentin. The effectiveness of the freezing-thawing protocol was confirmed by cultivation of limbal explants taken from non-cryopreserved cadaver corneoscleral rims. The result clearly showed that limbal tissue, subjected to cryopreservation and long lasting (up to 12 months) storage in liquid nitrogen, retains the capacity to be source of migrating and proliferating epithelial cells in vitro including the presumed adult stem cells and transient amplifying cells.

A clear cell variant of mucoepidermoid carcinoma harboring CRTC1-MAML2 fusion gene found in buccal mucosa: report of a case showing a large clear cell component and lacking typical epidermoid cells and intermediate cells.

PubMed

Tajima, Shogo; Namiki, Ichiro; Koda, Kenji

2017-06-01

The predominance of clear cells in mucoepidermoid carcinomas (MEC) is rare, and cases in which this occurs are termed clear cell variants of MEC. We present a case of a 70-year-old woman complaining of a right buccal mucosal mass, which had increased in size over 1 year. Histological examination revealed the mass to be composed predominantly of clear tumor cells, with mucin-containing cells and intermediate cell-like cells. Immunohistochemistry indicated that the tumor was positive for CK5/6 and p63, but negative for myoepithelial markers such as S-100 protein, αSMA, and calponin. These findings ruled out the possibility of a clear cell myoepithelial carcinoma, which is the most frequently observed type of salivary carcinoma composed predominantly of clear cells. However, it is difficult to distinguish between clear cell variants of MEC and hyalinizing clear cell carcinoma. Therefore, we performed fluorescence in situ hybridization to determine whether MAML2 rearrangement had occurred in this mass. Direct sequencing of the RT-PCR product demonstrated CRTC1-MAML2 fusion between exon 1 of CRTC1 and exon 2 of MAML2. Thus, the diagnosis of clear cell variant of MEC was confirmed. This is the first report of CRTC1-MAML2 fusion gene detection in a clear cell variant of MEC.

Comparison of Pyranometers and Reference Cells on Fixed and One-axis Tracking Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dooraghi, Michael R; Sengupta, Manajit; Vignola, Frank

Photovoltaic (PV) system perfomance is monitored by a wide variety of sensors. These instruments range from secondary standard pyranometers to photodiode-based pyranometers to reference cells. Although instruments are mounted in the plane of array of the modules a wide range of results have been obtained. Some of these difference have been assumed to come from systematic uncertainties associated with the irradiance sensors. This study is an attempt to quantify these differences by comparing the output of selected thermopile-based pyranometers to photodiode-based pyranometers and reference cells on a horizontal surface, a fixed-tilt surface, and a one-axis tracking surface. This analysis focusesmore » on clear-sky results from two sites with different climatic conditions. Several important features were observed. Photodiode-based pyranometers and reference cells produce widely different results under clear skies, especially at larger angles-of-incidence even though both instruments are based on measuring the short circuit current of solar cells. The difference is caused by the scattering of light as it passes through the glazing of the reference cell or the diffuser lens of the photodioded- base pyranometer. Both instruments are shown to have similar response to the spectral distribution of the irradiance when compared to the thermopile-based pyranometer that has a response nearly independent of the wavelength of light used by PV modules.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kajita, Shin, E-mail: kajita.shin@nagoya-u.jp; Hwangbo, Dogyun; Ohno, Noriyasu

In recent experiments, clear transitions in velocity and trail width of an arc spot initiated on nanostructured tungsten were observed on the boundary of the thick and thin nanostructured layer regions. The velocity of arc spot was significantly decreased on the thick nanostructured region. It was suggested that the grouping decreased the velocity of arc spot. In this study, we try to explain the phenomena using a simple random walk model that has properties of directionality and self-avoidance. And grouping feature was added by installing an attractive force between spot cells with dealing with multi-spots. It was revealed that anmore » entanglement of arc spot cells decreased the spot velocity, and spot cells tend to stamp at the same location many times.« less

[Clear cell carcinoma of the ovary simulating a yolk sac tumor].

PubMed

Bahri, Ibticem; Boudawara, Tahya; Khabir, Abdelmajid; Beyrouti, Mohamed Issam; Frikha, Mounir; Jlidi, Rachid

2003-04-01

Clear cell carcinoma (CCC) of the ovary is uncommon. In young patients, this tumor may simulate a yolk sac tumor. In this case, the morphologic distinction between these tumors is often difficult but the immunohistochemical staining for CA125 and alpha foeto protein (AFP) and the response to chemotherapy are particularly helpful to resolve this problem of differential diagnosis. We report a case of a 17 year old patient who was operated for a tumor of the right ovary. The diagnosis of a yolk sac tumor was first suggested. However, because of the non response to chemotherapy, a second laparotomy was performed; the definitive pathologic examination concluded to the diagnosis of a CCC of the ovary. The young age and the immunohistochemical staining for AFP are unusual and misleading features for a CCC. Our objective about this particular case is to discuss the anatomoclinical aspects of the CCC of the ovary and to prove the role of immunohistochemistry in the differential diagnosis.

Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia.

PubMed

Cario, Gunnar; Stanulla, Martin; Fine, Bernard M; Teuffel, Oliver; Neuhoff, Nils V; Schrauder, André; Flohr, Thomas; Schäfer, Beat W; Bartram, Claus R; Welte, Karl; Schlegelberger, Brigitte; Schrappe, Martin

2005-01-15

Treatment resistance, as indicated by the presence of high levels of minimal residual disease (MRD) after induction therapy and induction consolidation, is associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL). We hypothesized that treatment resistance is an intrinsic feature of ALL cells reflected in the gene expression pattern and that resistance to chemotherapy can be predicted before treatment. To test these hypotheses, gene expression signatures of ALL samples with high MRD load were compared with those of samples without measurable MRD during treatment. We identified 54 genes that clearly distinguished resistant from sensitive ALL samples. Genes with low expression in resistant samples were predominantly associated with cell-cycle progression and apoptosis, suggesting that impaired cell proliferation and apoptosis are involved in treatment resistance. Prediction analysis using randomly selected samples as a training set and the remaining samples as a test set revealed an accuracy of 84%. We conclude that resistance to chemotherapy seems at least in part to be an intrinsic feature of ALL cells. Because treatment response could be predicted with high accuracy, gene expression profiling could become a clinically relevant tool for treatment stratification in the early course of childhood ALL.

HMB-45 negative clear cell perivascular epithelioid cell tumor of the skin.

PubMed

Pusiol, Teresa; Morichetti, Doriana; Zorzi, Maria Grazia; Dario, Surace

2012-01-01

The first case of cutaneous clear cell perivascular epithelioid cell tumor (PEComa) with negative HMB-45 marker is presented. The tumor was a nodule 3x2 cm in size, located on the right foot in a 60-year-old man. The lesion consisted of large irregularly shaped cells with clear cytoplasm, negative for S-100 protein, HMB-45, Melan-A, pancytokeratin, epithelial membrane antigen and CAM5.2. Multifocal positivity for desmin, microphthalmia transcription factor and tyrosinase was found. The diagnosis of cutaneous PEComa of clear cell type was made. Clear cell change is a very unusual finding in PEComa and may pose problems in diagnostic differentiation from other clear cell cutaneous lesions that may be excluded with immunohistochemistry. In our case, the HMB-45 negativity may be explained by extensive clear cell change. Additional studies are necessary to accept the clear cell cutaneous HMB-45 negative PEComa as a new variant of perivascular epithelioid cell tumor.

Co-option of endocytic functions of cellular caveolae by pathogens

PubMed Central

Shin, J-S; Abraham, S N

2001-01-01

It is increasingly becoming clear that various immune cells are infected by the very pathogens that they are supposed to attack. Although many mechanisms for microbial entry exist, it appears that a common route of entry shared by certain bacteria, viruses and parasites involves cellular lipid-rich microdomains sometimes called caveolae. These cellular entities, which are characterized by their preferential accumulation of glycosylphosphatidylinositol (GPI)-anchored molecules, cholesterol and various glycolipids, and a distinct protein (caveolin), are present in many effector cells of the immune system including neutrophils, macrophages, mast cells and dendritic cells. These structures have an innate capacity to endocytoze various ligands and traffic them to different intracellular sites and sometimes, back to the extracellular cell surface. Because caveolae do not typically fuse with lysosomes, the ligands borne by caveolar vesicles are essentially intact, which is in marked contrast to ligands endocytozed via the classical endosome–lysosome pathway. A number of microbes or their exotoxins co-opt the unique features of caveolae to enter and traffic, without any apparent loss of viability and function, to different sites within immune and other host cells. In spite of their wide disparity in size and other structural attributes, we predict that a common feature among caveolae-utilizing pathogens and toxins is that their cognate receptor(s) are localized within plasmalemmal caveolae of the host cell. PMID:11168630

Accurate label-free 3-part leukocyte recognition with single cell lens-free imaging flow cytometry.

PubMed

Li, Yuqian; Cornelis, Bruno; Dusa, Alexandra; Vanmeerbeeck, Geert; Vercruysse, Dries; Sohn, Erik; Blaszkiewicz, Kamil; Prodanov, Dimiter; Schelkens, Peter; Lagae, Liesbet

2018-05-01

Three-part white blood cell differentials which are key to routine blood workups are typically performed in centralized laboratories on conventional hematology analyzers operated by highly trained staff. With the trend of developing miniaturized blood analysis tool for point-of-need in order to accelerate turnaround times and move routine blood testing away from centralized facilities on the rise, our group has developed a highly miniaturized holographic imaging system for generating lens-free images of white blood cells in suspension. Analysis and classification of its output data, constitutes the final crucial step ensuring appropriate accuracy of the system. In this work, we implement reference holographic images of single white blood cells in suspension, in order to establish an accurate ground truth to increase classification accuracy. We also automate the entire workflow for analyzing the output and demonstrate clear improvement in the accuracy of the 3-part classification. High-dimensional optical and morphological features are extracted from reconstructed digital holograms of single cells using the ground-truth images and advanced machine learning algorithms are investigated and implemented to obtain 99% classification accuracy. Representative features of the three white blood cell subtypes are selected and give comparable results, with a focus on rapid cell recognition and decreased computational cost. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Future perspectives for diagnostic imaging in urology: from anatomic and functional to molecular imaging].

PubMed

Macis, Giuseppe; Di Giovanni, Silvia; Di Franco, Davide; Bonomo, Lorenzo

2013-01-01

The future approach of diagnostic imaging in urology follows the technological progress, which made the visualization of in vivo molecular processes possible. From anatomo-morphological diagnostic imaging and through functional imaging molecular radiology is reached. Based on molecular probes, imaging is aimed at assessing the in vivo molecular processes, their physiology and function at cellular level. The future imaging will investigate the complex tumor functioning as metabolism, aerobic glycolysis in particular, angiogenesis, cell proliferation, metastatic potential, hypoxia, apoptosis and receptors expressed by neoplastic cells. Methods for performing molecular radiology are CT, MRI, PET-CT, PET-MRI, SPECT and optical imaging. Molecular ultrasound combines technological advancement with targeted contrast media based on microbubbles, this allowing the selective registration of microbubble signal while that of stationary tissues is suppressed. An experimental study was carried out where the ultrasound molecular probe BR55 strictly bound to prostate tumor results in strong enhancement in the early phase after contrast, this contrast being maintained in the late phase. This late enhancement is markedly significant for the detection of prostatic cancer foci and to guide the biopsy sampling. The 124I-cG250 molecular antibody which is strictly linked to cellular carbonic anhydrase IX of clear cell renal carcinoma, allows the acquisition of diagnostic PET images of clear cell renal carcinoma without biopsy. This WG-250 (RENCAREX) antibody was used as a therapy in metastatic clear cell renal carcinoma. Future advancements and applications will result in early cancer diagnosis, personalized therapy that will be specific according to the molecular features of cancer and leading to the development of catheter-based multichannel molecular imaging devices for cystoscopy-based molecular imaging diagnosis and intervention.

The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma.

PubMed

Miess, Heike; Dankworth, Beatrice; Gouw, Arvin M; Rosenfeldt, Mathias; Schmitz, Werner; Jiang, Ming; Saunders, Becky; Howell, Michael; Downward, Julian; Felsher, Dean W; Peck, Barrie; Schulze, Almut

2018-06-05

Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis. Moreover, silencing of enzymes of the GSH biosynthesis pathway or glutathione peroxidases, which depend on GSH for the removal of cellular hydroperoxides, selectively reduced viability of ccRCC cells but did not affect the growth of non-malignant renal epithelial cells. Inhibition of GSH synthesis triggered ferroptosis, an iron-dependent form of cell death associated with enhanced lipid peroxidation. VHL is a major tumour suppressor in ccRCC and loss of VHL leads to stabilisation of hypoxia inducible factors HIF-1α and HIF-2α. Restoration of functional VHL via exogenous expression of pVHL reverted ccRCC cells to an oxidative metabolism and rendered them insensitive to the induction of ferroptosis. VHL reconstituted cells also exhibited reduced lipid storage and higher expression of genes associated with oxidiative phosphorylation and fatty acid metabolism. Importantly, inhibition of β-oxidation or mitochondrial ATP-synthesis restored ferroptosis sensitivity in VHL reconstituted cells. We also found that inhibition of GSH synthesis blocked tumour growth in a MYC-dependent mouse model of renal cancer. Together, our data suggest that reduced fatty acid metabolism due to inhibition of β-oxidation renders renal cancer cells highly dependent on the GSH/GPX pathway to prevent lipid peroxidation and ferroptotic cell death.

Coupling between apical tension and basal adhesion allow epithelia to collectively sense and respond to substrate topography over long distances.

PubMed

Broaders, Kyle E; Cerchiari, Alec E; Gartner, Zev J

2015-12-01

Epithelial sheets fold into complex topographies that contribute to their function in vivo. Cells can sense and respond to substrate topography in their immediate vicinity by modulating their interfacial mechanics, but the extent to which these mechanical properties contribute to their ability to sense substrate topography across length scales larger than a single cell has not been explored in detail. To study the relationship between the interfacial mechanics of single cells and their collective behavior as tissues, we grew cell-sheets on substrates engraved with surface features spanning macroscopic length-scales. We found that many epithelial cell-types sense and respond to substrate topography, even when it is locally nearly planar. Cells clear or detach from regions of local negative curvature, but not from regions with positive or no curvature. We investigated this phenomenon using a finite element model where substrate topography is coupled to epithelial response through a balance of tissue contractility and adhesive forces. The model correctly predicts the focal sites of cell-clearing and epithelial detachment. Furthermore, the model predicts that local tissue response to substrate curvature is a function of the surrounding topography of the substrate across long distances. Analysis of cell-cell and cell-substrate contact angles suggests a relationship between these single-cell interfacial properties, epithelial interfacial properties, and collective epithelial response to substrate topography. Finally, we show that contact angles change upon activation of oncogenes or inhibition of cell-contractility, and that these changes correlate with collective epithelial response. Our results demonstrate that in mechanically integrated epithelial sheets, cell contractility can be transmitted through multiple cells and focused by substrate topography to affect a behavioral response at distant sites.

Cytologic Features of Renal Carcinoma Associated with Xp11.2 Translocations/ TFE3 Gene Fusions: A Case Report with Voided and Catheterized Urine Cytology and a Literature Review.

PubMed

Kuwamoto, Satoshi; Murai, Yuki; Endo, Yukari; Masago, Toshihiko; Kuroda, Naoto; Horie, Yasushi

2014-01-01

Renal carcinomas associated with Xp11.2 translocations/TFE3 gene fusions are rare subtypes of renal neoplasm that predominantly occur in younger individuals. There are very few reports describing the cytologic features of these tumors. A 27-year-old man presented with hematuria and was found to have a mass in the lower part of the right kidney. Cytology of catheterized urine obtained from the right renal pelvis showed clusters of cells with abundant clear or eosinophilic granular cytoplasm, large round nuclei and prominent nucleoli. Papillary clusters containing thin fibrous stroma were occasionally seen. Voided urine cytology showed similar cell clusters but degeneration made the features obscure. Nephroureterectomy revealed a renal tumor showing a mixed papillary and nested architecture. The diagnosis was confirmed by immunohistochemistry and fluorescence in situ hybridization. The present case indicates that the characteristic features of these tumor subtypes can be retained in urine cytology. Cytology may be enough to suspect these tumors as part of the differential diagnosis when the patient's age and imaging findings are taken into account and may facilitate further studies for a definitive diagnosis. © 2014 S. Karger AG, Basel.

SWI/SNF Protein Expression Status in Fumarate Hydratase-deficient Renal Cell Carcinoma: Immunohistochemical Analysis of 32 Tumors from 28 Patients.

PubMed

Agaimy, Abbas; Amin, Mahul B; Gill, Anthony J; Popp, Bernt; Reis, André; Berney, Daniel M; Magi-Galluzzi, Cristina; Sibony, Mathilde; Smith, Steven C; Suster, Saul; Trpkov, Kiril; Hes, Ondřej; Hartmann, Arndt

2018-04-21

Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare, aggressive RCC type, originally described in the setting of hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome which is defined by germline FH gene inactivation. Inactivation of components of the SWI/SNF chromatin remodelling complex is involved in renal medullary carcinoma (SMARCB1/INI1 loss), clear cell RCC (PBRM1 loss) and in subsets of dedifferentiated RCC of clear cell, chromophobe and papillary types (loss of different SWI/SNF components). FH-RCC and SWI/SNF-deficient RCC share anaplastic nuclear features and highly aggressive course. We analysed 32 FH-RCCs from 28 patients using seven commercially available SWI/SNF antibodies (SMARCB1/INI1, SMARCA2, SMARCA4, SMARCC1, SMARCC2, PBRM1 and ARID1A). Variable loss of SMARCB1, ARID1A and SMARCC1 was observed in 1/31, 2/31 and 1/29 evaluable cases, respectively; three of these four SWI/SNF-deficient tumors had confirmed FH mutations. No correlation of SWI/SNF loss with solid or sarcomatoid features was observed. Two tumors with SMARCB1 and ARID1A deficiency had available SWI/SNF molecular data; both lacked SMARCB1 and ARID1A mutations. The remaining five SWI/SNF components were intact in all cases. Especially PBRM1 seems not to be involved in the pathogenesis or progression of FH-deficient RCC. Our data showed that, a subset of FH-RCC (12%) have a variable loss of SWI/SNF complex subunits, likely as secondary genetic events. This should not be confused with SWI/SNF-deficient RCC of other types. Evaluation of FH and SWI/SNF together with comprehensive molecular-genetic profiling is needed to explore possible prognostic implications of FH/SWI-SNF double deficiency and to better understand the somatic mutation landscape in high-grade RCC. Copyright © 2018. Published by Elsevier Inc.

Perivascular Epithelioid Cell Tumor of the Uterus with Ovarian Involvement: A Case Report and Review of the Literature.

PubMed

Fitzpatrick, Megan; Pulver, Tanya; Klein, Molly; Murugan, Paari; Khalifa, Mahmoud; Amin, Khalid

2016-05-06

Perivascular epithelioid cell tumors (PEComas) are a rare group of neoplasms composed of epithelioid cells that express both melanocytic and myoid markers. When considering PEComas of the female genital tract, the uterus is the most common location. Involvement of the ovary in the context of a primary uterine PEComa, in the absence of systemic disease associated with tuberous sclerosis, however, has only been reported in 1 previous case. We report a case of a PEComa of the uterus with metastasis to the left ovary in a 61-year-old Caucasian woman. Gross examination of the uterus revealed a 10.7×10.5×10.2 cm tan-brown, mostly solid, partially cystic mass. Microscopic examination showed epithelioid cells with clear to eosinophilic cytoplasm, arranged in fascicles. Intranuclear pseudoinclusions were also noted. The tumor cells were smooth muscle actin, caldesmon, and desmin positive (diffuse); HMB-45 positive (focal); and Melan-A, AE1/AE3, CD10, and S100 negative by immunohistochemistry. Distinguishing among mesenchymal neoplasms, including PEComas, endometrial stromal sarcomas, and leiomyosarcomas, can be difficult. Careful analysis of morphologic and immunohistochemical features is of the utmost importance. Differential diagnosis, including morphologic features and immunohistochemical patterns, is also discussed.

Adipogenesis of the mesenchymal stromal cells and bone oedema in rheumatoid arthritis.

PubMed

Okada, A; Yamasaki, S; Koga, T; Kawashiri, S Y; Tamai, M; Origuchi, T; Nakamura, H; Eguchi, K; Kawakami, A

2012-01-01

Bone oedema is a pathological change in rheumatoid arthritis (RA) that is detectable by magnetic resonance imaging (MRI). Recent histological analyses revealed that a prominent feature of bone oedema is the replacement of adipose tissue with inflammatory cells. Here, we demonstrate the possible roles of mesenchymal stromal cells (MSCs) in bone oedema formation and the pathogenic potential of the cells in RA. Adipogenesis of bone marrow-derived human MSCs was induced by a standard adipogenic induction medium in the presence or absence of cytokines. The cytokine productions from MSCs were screened by an antibody array system and confirmed by ELISA. The migration assay was performed to determine the locomotive abilities of undifferentiated MSCs or MSCs after adipogenesis. The expression of α smooth muscle actin (SMA) and F-actin was examined by immunostaining and phalloidin staining, respectively. TNF-α, interleukin (IL)-1β, IL-6, and TGF-β clearly inhibited the adipogenesis of MSCs. Production of IL-6 was markedly reduced, and IL-8 secretion was augmented in MSCs after adipogenesis. The mobility of MSCs after adipogenesis was clearly reduced in migration assays compared to that of undifferentiated MSCs. Consistent with these findings, SMA and F-actin expressions were clearly suppressed in MSCs committed to adipogenesis. Our data suggest that the inflammatory milieu promotes bone oedema by blocking adipogenesis of MSCs. In bone oedema, the enhanced IL-6 production and the increased mobility of MSCs may contribute to the progression of RA. Therefore, bone oedema may be an important target lesion in the treatment of RA.

Advanced nanobiomaterial strategies for the development of organized tissue engineering constructs.

PubMed

An, Jia; Chua, Chee Kai; Yu, Ting; Li, Huaqiong; Tan, Lay Poh

2013-04-01

Nanobiomaterials, a field at the interface of biomaterials and nanotechnologies, when applied to tissue engineering applications, are usually perceived to resemble the cell microenvironment components or as a material strategy to instruct cells and alter cell behaviors. Therefore, they provide a clear understanding of the relationship between nanotechnologies and resulting cellular responses. This review will cover recent advances in nanobiomaterial research for applications in tissue engineering. In particular, recent developments in nanofibrous scaffolds, nanobiomaterial composites, hydrogel systems, laser-fabricated nanostructures and cell-based bioprinting methods to produce scaffolds with nanofeatures for tissue engineering are discussed. As in native niches of cells, where nanofeatures are constantly interacting and influencing cellular behavior, new generations of scaffolds will need to have these features to enable more desirable engineered tissues. Moving forward, tissue engineering will also have to address the issues of complexity and organization in tissues and organs.

Filopodia and Viruses: An Analysis of Membrane Processes in Entry Mechanisms

PubMed Central

Chang, Kenneth; Baginski, John; Hassan, Samer F.; Volin, Michael; Shukla, Deepak; Tiwari, Vaibhav

2016-01-01

Filopodia are thin, actin rich bundles protruding from cell plasma membranes, serving physiological purposes, such as probing the environment and facilitating cell-to-cell adhesion. Recent studies have highlighted that actively polymerized filopodial-protrusions are exploited during virus entry, trafficking, spread, and the development of clinical pathology of viral diseases. These observations have caused a surge in investigation of the key determinants of filopodial induction and their influence on cell topography including receptor expression for viral entry. It is now very clear that filopodia can provide unique opportunities for many viruses to invade host cells vertically during primary infection, or horizontally during virus spread from cell-to-cell. These emerging concepts can explain the unprecedented ability of viruses to invade both nearby and long-distant host cells, a feature that may directly contribute to viral tropism. In this review, we summarize the significance of filopodia in viral diseases and discuss future therapeutic possibilities to precisely target filopodial-flyovers to prevent or control infectious diseases. PMID:27014223

Biomarker-specific conjugated nanopolyplexes for the active coloring of stem-like cancer cells

NASA Astrophysics Data System (ADS)

Hong, Yoochan; Lee, Eugene; Choi, Jihye; Haam, Seungjoo; Suh, Jin-Suck; Yang, Jaemoon

2016-06-01

Stem-like cancer cells possess intrinsic features and their CD44 regulate redox balance in cancer cells to survive under stress conditions. Thus, we have fabricated biomarker-specific conjugated polyplexes using CD44-targetable hyaluronic acid and redox-sensible polyaniline based on a nanoemulsion method. For the most sensitive recognition of the cellular redox at a single nanoparticle scale, a nano-scattering spectrum imaging analyzer system was introduced. The conjugated polyplexes showed a specific targeting ability toward CD44-expressing cancer cells as well as a dramatic change in its color, which depended on the redox potential in the light-scattered images. Therefore, these polyaniline-based conjugated polyplexes as well as analytical processes that include light-scattering imaging and measurements of scattering spectra, clearly establish a systematic method for the detection and monitoring of cancer microenvironments.

Aspects of vertebrate gustatory phylogeny: morphology and turnover of chick taste bud cells.

PubMed

Ganchrow, J R; Ganchrow, D; Royer, S M; Kinnamon, J C

1993-10-01

The taste bud is a receptor form observed across vertebrates. The present report compares chick taste buds to those of other vertebrates using light and electron microscopy. Unlike mammals, but common to many modern avians, the dorsal surface of chick anterior tongue lacks taste papillae and taste buds. Ultrastructurally, chick buds located in the anterior floor of the mouth (as in some reptiles and amphibians) and palate contain dark, intermediate, light, and basal cell types. Dark, intermediate, and light cells extend microvilli into intragemmal lumina and pores communicating with the oral cavity. As specialized features, dark cell apices lack dense granules and exhibit short microvilli relative to light and intermediate cells. Dark cell cytoplasmic fingers envelop intragemmal nerve fibers and cells as in other species, and sometimes contain abundant clear vesicles. Nerve profile expansions often are located adjacent to dark, intermediate, and light cell nuclei. Classical afferent synaptic contacts are rarely observed. Taste cell turnover is suggested by mitotic and degenerating figures in chick buds. In addition, tritiated thymidine injected into hatchlings, whose anterior mandibular oral taste bud population approximates that in adults, reveals a turnover rate of about 4.5 days. This is about half that observed in altricial mammals, reflecting a species difference or developmental factor in precocial avians. It is concluded that chick taste buds exhibit morphologic features common to other vertebrate buds with specializations reflecting the influences of niche, glandular relations, and/or age.

Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells

PubMed Central

Yin, Yan; Lin, Congxing; Veith, G. Michael; Chen, Hong; Dhandha, Maulik; Ma, Liang

2012-01-01

SUMMARY Developmental exposure to diethylstilbestrol (DES) causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of peroxisome proliferator-activated receptor-γ (PPARγ)-mediated adipogenesis and lipid metabolism, including PPARγ itself, are targets of DES in the neonatal uterus. Transmission electron microscopy and Oil-Red O staining further demonstrate a dramatic increase in lipid deposition in uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor-induced reproductive abnormalities. PMID:22679223

Diabetes and Risk of Renal Cell Carcinoma

PubMed Central

Habib, Samy L; Prihoda, Thomas J; Luna, Maria; Werner, Sherry A

2012-01-01

Background and objectives: There is evidence that the incidence of solid tumors is markedly increased in patients with diabetes mellitus. In the current study, we investigate the association between diabetes and renal cancer. Patients and Methods: A single-center retrospective analysis of 473 patients who underwent nephrectomy for renal cell carcinoma (RCC) was performed. Diabetic RCC patients were screened for age, gender, ethnicity, HgA1C, glucose levels and renal function. Results: Of the 473 cases with RCC, we identified 120 patients (25.4%) with a history of diabetes. The incidence of diabetes in RCC patients was higher in female than male subjects and in Hispanic compared to White and Other ethnic backgrounds. At diagnosis, the majority of diabetic RCC patients were 50-59 years of age. In diabetic RCC cases, clear cell type histology (92.0%), nuclear grade 2 (56.1%) and tumor size range from 1-5 cm (65.7%) were the most common in each category. Conclusion: Our findings indicate that diabetic RCC patients have a predominance of localized, small clear cell RCC. In addition, females with a history of RCC have a higher frequency of diabetes compared to males. This is the first report of clinical and histopathological features of RCC associated with diabetes. PMID:22232697

An unusual presentation of adult Wilms' tumor.

PubMed

Mydlo, J H; Horowitz, M; Del Rosario, C; Cosgrove, J; Macchia, R J

1996-01-01

Wilms' tumor (nephroblastoma), a primary renal neoplasm containing primitive blastema and embryonic glomerulotubular structures, is the most common malignant tumor of the urinary tract in children. There have been about 240 cases of adult Wilms' tumor reported in the world literature, however due to some differences in histologic findings, many cases have been reclassified as rhabdoid or clear cell sarcomas, both of which are recognized as separate entities. We report a case of an adult Wilms' tumor and discuss the clinical, radiographic and histologic features of this tumor.

Clear cell variant of follicular thyroid carcinoma with normal thyroid-stimulating hormone value: a case report

PubMed Central

2014-01-01

Introduction Clear cell carcinomas of the thyroid gland with normal thyroid-stimulating hormone value are very rare, but clear cell changes are described in most reported cases of thyroidal lesions. Case presentation In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor was 1cm in diameter and consisted of pure clear cells. Conclusion Clear cell variants of follicular thyroid carcinoma are rarely seen, especially it is misdiagnosed with metastatic renal cell carcinoma. In this report, we describe the case of a patient with a clear cell variant of follicular thyroid carcinoma with an interesting pathology. PMID:24884725

Observed Properties of Giant Cells

NASA Technical Reports Server (NTRS)

Hathaway, David H.; Upton, Lisa; Colegrove, Owen

2014-01-01

The existence of Giant Cells has been suggested by both theory and observation for over 45 years. We have tracked the motions of supergranules in SDO/HMI Doppler velocity data and find larger (Giant Cell) flows that persist for months. The flows in these cells are clockwise around centers of divergence in the north and counter-clockwise in the south. Equatorward flows are correlated with prograde flows - giving the transport of angular momentum toward the equator that is needed to maintain the Sun's rapid equatorial rotation. The cells are most pronounced at mid- and high-latitudes where they exhibit the rotation rates representative of those latitudes. These are clearly large, long-lived, cellular features, with the dynamical characteristics expected from the effects of the Sun's rotation, but the shapes of the cells are not well represented in numerical models. While the Giant Cell flow velocities are small (<10 m/s), their long lifetimes should nonetheless substantially impact the transport of magnetic flux in the Sun's near surface layers.

Angiofibroma of soft tissue with fibrohistiocytic features and intratumor genetic heterogeneity of NCOA2 gene rearrangement revealed by chromogenic in situ hybridization: a case report.

PubMed

Fukuda, Yumiko; Motoi, Toru; Kato, Ikuma; Ikegami, Masachika; Funata, Nobuaki; Ohtomo, Rie; Horiguchi, Shinichiro; Goto, Takahiro; Hishima, Tsunekazu

2014-05-01

Angiofibroma of soft tissue is a recently described soft tissue tumor that is characterized by fibroblastic spindle tumor cells with arborizing capillary proliferation. Cytogenetically, it harbors a specific fusion gene involving the nuclear receptor coactivator 2 (NCOA2) gene. We report here additional new pathological and cytogenetic features. A soft tissue tumor in the left thigh of 73-year-old female was investigated. Microscopically, histiocytoid tumor cells were scattered in an edematous background with branching capillary proliferation. Immunohistochemically, we identified that the tumor cells were positive for histiocytic markers such as CD68 and CD163. Rearrangement of the NCOA2 gene was detected successfully by chromogenic in situ hybridization; however, abnormal signal patterns were observed in only a small subset of tumor cells. Unlike typical tumors with bland spindle cells, the present tumor needs to be distinguished from myxoid, dendritic and clear cell tumors. This case may suggest that angiofibroma of soft tissue is not in the center of the fibroblastic/myofibroblastic tumor group, but rather shows a fibrohistiocytic nature. We also found intratumor genetic heterogeneity, which is uncommon for a translocation-associated tumor. Therefore, careful evaluation is required to detect the gene rearrangement in this tumor entity. © 2014 The Authors. Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Perivascular epithelioid cell tumor (PEComa) of gynecologic origin: a clinicopathological study of three cases.

PubMed

Ye, H Y; Chen, J G; Luo, D L; Jiang, Z M; Chen, Z H

2012-01-01

Perivascular epithelioid cell tumors (PEComas), occasionally associated with the tuberous sclerosis complex, are characterized by varying amounts of spindle and epithelioid cells with clear to eosinophilic cytoplasm that display immunoreactivity for melanocytic markers, most frequently HMB-45. Perivascular epithelioid cell tumor of gynecologic origin is very rare, and there have been only a few reported cases. This study describes the clinical, histological, and immunohistochemical features and prognoses of three cases of gynecologic origin. Two of the three tumors were confined to the uterus and one to the vagina. None of the patients had tuberous sclerosis complex. Immunohistochemistry indicated that all three cases expressed at least one melanocytic marker, and HMB45 was a positive marker for all of them. These markers can be found in both epithelial cells and spindle cells. Except for MiTF, which was located in the nucleus, all the other antibodies were located in the cytoplasm. The three cases have been followed up for 26, 22, and three months, respectively, with disease-free survival in all cases. We conclude that PEComas of gynecologic origin have morphological and immunohistochemical features of the PEComa family, which are rare and should be included in the differential diagnosis with other tumors. Until more cases of this rare tumor are evaluated with longer follow-up, firm criteria for malignancy remain uncertain.

Water-clear cell adenoma of the parathyroid. A case report with immunohistochemistry and electron microscopy.

PubMed

Grenko, R T; Anderson, K M; Kauffman, G; Abt, A B

1995-11-01

We report a water-clear cell adenoma of the parathyroid gland, a lesion which to our knowledge has not been described previously. Like its rare but well-described hyperplastic counterpart, water-clear cell hyperplasia, this adenoma is composed of cells with abundant foamy-to-granular cytoplasm and mild nuclear pleomorphism. The cells form glandular structures and cell nests separated by fine fibrovascular septae. The tumor cells stain positively with anti-parathyroid hormone and show characteristic glassy and flocculate material by electron microscopy. Unlike water-clear cell hyperplasia, water-clear cell adenoma is a solitary lesion that compresses the residual nonneoplastic parathyroid gland.

Inductive phenomena at low frequencies in impedance spectra of proton exchange membrane fuel cells - A review

NASA Astrophysics Data System (ADS)

Pivac, Ivan; Barbir, Frano

2016-09-01

The results of electrochemical impedance spectroscopy of proton exchange membrane (PEM) fuel cells may exhibit inductive phenomena at low frequencies. The occurrence of inductive features at high frequencies is explained by the cables and wires of the test system. However, explanation of inductive loop at low frequencies requires a more detailed study. This review paper discusses several possible causes of such inductive behavior in PEM fuel cells, such as side reactions with intermediate species, carbon monoxide poisoning, and water transport, also as their equivalent circuit representations. It may be concluded that interpretation of impedance spectra at low frequencies is still ambiguous, and that better equivalent circuit models are needed with clearly defined physical meaning of each of the circuit elements.

[Endometrial carcinomas and precursor lesions--new aspects].

PubMed

Schmidt, D

2009-07-01

Endometrial carcinomas can be separated into two groups which are designated as type I and type II carcinomas today. Both groups of tumors are clearly different with regard to conventional light microscopy, immunohistochemistry, molecular pathology and clinical features. Only type I carcinomas are associated with hyperestrogenism. The group of type I carcinomas consists of endometrioid carcinoma and its variants, and mucinous carcinoma. The prototypes of type II carcinomas are serous and clear cell carcinoma. Not all carcinomas, however, can be assigned to one of the two groups, because there are hybrid tumors and mixed carcinomas, e.g. endometrioid carcinoma with a serous component. The precursor lesions of the endometrioid carcinoma and the serous carcinoma are well characterized morphologically and by molecular pathology. Atypical hyperplasia is the precursor lesion of endometrioid carcinoma, whereas endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma. No precursor lesion has as yet been identified for clear cell carcinoma. Immunohistochemical markers for endometrial carcinoma are CK7 and vimentin, for serous carcinoma markers are p53 and p16. Correct typing is of essential prognostic necessity in endometrial carcinoma. Of utmost importance is the detection of a serous component, because serous carcinoma leads to early tumor spread with the necessity of radical surgery, chemotherapy and radiotherapy.

Comparison of ThinPrep and conventional preparations on fine needle aspiration cytology material.

PubMed

Dey, P; Luthra, U K; George, J; Zuhairy, F; George, S S; Haji, B I

2000-01-01

To compare the various cytologic features on ThinPrep 2000 (TP) (Cytyc Corporation, Marlborough, Massachusetts, U.S.A.) and conventional preparation (CP) specimens from fine needle aspiration cytology (FNAC) material by a semiquantitative scoring system. In this prospective study a total of 71 consecutive cases were included. In each case, two passes were performed. The first pass was used for conventional preparations, with direct smears made and fixed immediately in 95% alcohol for Papanicolaou stain. For TP preparation a second pass produced material for processing in the ThinPrep 2000. The TP and CP slides were studied independently by two observers and representative slides of CP and TP compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of monolayer cells, and nuclear and cytoplasmic details by a semiquantitative scoring system. Statistical analysis was performed by Wilcoxon's signed rank test on an SPSS program (Chicago, Illinois, U.S.A.). TP preparations contained adequate diagnostic cells in all cases and were tangibly superior to CP preparations concerning monolayer cells, absence of blood and necrosis, and preservation of nuclear and cytoplasmic detail (statistically significant, Wilcoxon's signed rank test, P < .000). TP preparations are superior to conventional preparations with regard to clear background, monolayer cell preparation and cell preservation. It is easier and less time consuming to screen and interpret TP preparations because the cells are limited to smaller areas on clear backgrounds, with excellent cellular preservation. However, TP preparations are more expensive than CP and require some experience for interpretation.

Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

PubMed

Fadare, Oluwole; Liang, Sharon X

2012-12-01

Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear cell metaplasia) displayed some degree of HNF1β immunoreactivity, with an average nuclear staining score of 7.3. We conclude that although HNF1β is frequently expressed in clear cell carcinomas, it should be used with caution as a diagnostic marker because of its lack of specificity. It neither distinguishes endometrial serous carcinomas from clear cell carcinomas nor clear cell carcinomas from its benign mimics. The greatest diagnostic utility of HNF1β expression may be in a supportive evidentiary role favoring clear cell carcinoma when the principal differential diagnostic consideration is endometrioid carcinoma.

Altered expression of key cell cycle regulators in renal cell carcinoma associated with Xp11.2 translocation.

PubMed

Barroca, H; Castedo, S; Vieira, J; Teixeira, M; Müller-Höcker, J

2009-01-01

Renal cell carcinoma (RCC) is a rare tumor in the pediatric population. Recently, a phenotypically and genetically distinct kidney carcinoma, mainly prevalent in children and associated with an Xp11.2 translocation or TFE3 gene fusion, has been described. It has been advanced that in this subtype of RCC, there is an accumulation of cyclin D1, cyclin D3, and p21 ((wafl/cip1)). The aim of the present study was to figure out in two pediatric RCC recently diagnosed in our department (one clear cell-type RCC and one TFE3-positive RCC) whether those features are indeed specific of the latter tumor or occur in pediatric RCC irrespective of the tumor type. The following immunostains were performed in both cases: Ki67, p16(ink4a), p21 ((wafl/cip1)), p27(kip1), p53, p63, mdm2, cyclin D1, cyclin D3, TFE3, CD10, vimentin, E-cadherin, and RCC-antigen. We observed in the TFE3-positive carcinoma an intense immunoreaction for p21 ((wafl/cip1)), cyclin D1, and cyclin D3, without expression for p53, p16, p27(kip1), and mdm2, whereas the immunoexpression profile observed in the classic RCC was similar to that of clear cell, adult-type RCC. Our study confirms that TFE3-positive RCC exhibits a deregulation of the cell cycle apparently unrelated to the young age of the patients.

Comparison of Pyranometers and Reference Cells on Fixed and One-Axis Tracking Surfaces: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dooraghi, Michael R; Sengupta, Manajit; Vignola, Frank

A wide variety of sensors are used to monitor the irradiance incident on solar modules to evaluate the performance of photovoltaic (PV) systems. These instruments range from secondary standard pyranometers to photodiode-based pyranometers to reference cells. Although instruments are mounted in the plane of array of the modules, a wide range of results have been obtained. Some of these difference have been assumed to come from systematic uncertainties associated with the irradiance sensors. This study is an attempt to quantify these differences by comparing the output of selected thermopile pyranometers to photodiode-based pyranometers and reference cells on a horizontal surface,more » a fixed-tilt surface, and a one-axis tracking surface. This analysis focuses on clear-sky results from two sites with different climatic conditions. Several important features were observed. Photodiode-based pyranometers and reference cells produce widely different results under clear skies, especially at larger angles of incidence, even though both instruments are based on measuring the short-circuit current of solar cells. The difference is caused by the scattering of light as it passes through the glazing of the reference cell or the diffuser lens of the photodioded-base pyranometer. Both instruments are shown to have similar response to the spectral distribution of the irradiance when compared to the thermopile-based pyranometer, which has a response nearly independent of the wavelength of light used by PV modules.« less

[New features in the 2014 WHO classification of uterine neoplasms].

PubMed

Lax, S F

2016-11-01

The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma). Besides a papillary architecture serous carcinomas may show solid and glandular features and TP53 immunohistochemistry with an "all or null pattern" assists in the diagnosis of serous carcinoma with ambiguous features. Neuroendocrine neoplasms are categorized in a similar way to the gastrointestinal tract into well differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas (small cell and large cell types). Leiomyosarcomas of the uterus are typically high grade and characterized by marked nuclear atypia and lively mitotic activity. Low grade stromal neoplasms frequently show gene fusions, such as JAZF1/SUZ12. High grade endometrial stromal sarcoma is newly defined by cyclin D1 overexpression and the presence of the fusion gene YWHAE/FAM22 and must be distinguished from undifferentiated uterine sarcoma. Carcinosarcomas (malignant mixed Mullerian tumors MMMT) show biological and molecular similarities to high-grade carcinomas.

Linking minds and brains.

PubMed

Barlow, Horace

2013-11-01

When I first came across William James' dictum that " … this sense of sameness is the very keel and backbone of our thinking," I thought he had foreseen the importance of cross-correlation in the brain, and told myself to find out how he had reached this conclusion. When I finally did this a year or two ago, I slowly came to realize that I had completely misunderstood him; from the full quote it is absolutely clear that his dictum cannot be referring to the process by which a cortical simple cell responds selectively to the orientation of features in a visual image, as I had originally supposed. If one translates the original dictum into two more prosaic modern versions, his version would say: "Our minds could not think at all without neural circuits in our brains that compute auto-correlations," but in my mistaken interpretation the last word would be "cross-correlations." Others may have made the same mistake, but the difference is profound, and finding what he really meant has been a revelation to me. This essay explains the revelation, describes how to determine experimentally whether the brain does auto- or cross-correlation, and gives the result of preliminary experiments showing clearly that it does both. A revised view of the visual cortex as autocorrelator as well as cross-correlator claims to tell us what complex cells in the visual cortex do, and it assigns a role to its columnar structure that is as important to fulfilling that role as the concept of the receptive field has been to understanding the simple cells' fulfillment of theirs. The new view has compelling features, broad implications, and suggests a plausible model of how neural circuits in the cortex achieve thought, but it needs further testing.

Adult pituitary stem cells: from pituitary plasticity to adenoma development.

PubMed

Florio, Tullio

2011-01-01

The pituitary needs high plasticity of the hormone-producing cell compartment to generate the continuously changing hormonal signals that govern the key physiological processes it is involved in, as well as homeostatic cell turnover. However, the underlying mechanisms are still poorly understood. It was proposed that adult stem cells direct the generation of newborn cells with a hormonal phenotype according to the physiological requirements. However, only in recent years adult pituitary stem cells have begun to be phenotypically characterized in several studies that identified multiple stem/progenitor cell candidates. Also considering the incompletely defined features of this cell subpopulation, some discrepancies among the different reports are clearly apparent and long-term self-renewal remains to be unequivocally demonstrated. Here, all the recently published evidence is analyzed, trying, when possible, to reconcile the results of the different studies. Finally, with the perspective of shedding light on pituitary tumorigenesis and the development of potentially new pharmacological approaches directed against these cells, very recent evidence on the presence of putative cancer stem cells in human pituitary adenomas is discussed. Copyright © 2011 S. Karger AG, Basel.

Interstitial Cells: Regulators of Smooth Muscle Function

PubMed Central

Sanders, Kenton M.; Ward, Sean M.; Koh, Sang Don

2014-01-01

Smooth muscles are complex tissues containing a variety of cells in addition to muscle cells. Interstitial cells of mesenchymal origin interact with and form electrical connectivity with smooth muscle cells in many organs, and these cells provide important regulatory functions. For example, in the gastrointestinal tract, interstitial cells of Cajal (ICC) and PDGFRα+ cells have been described, in detail, and represent distinct classes of cells with unique ultrastructure, molecular phenotypes, and functions. Smooth muscle cells are electrically coupled to ICC and PDGFRα+ cells, forming an integrated unit called the SIP syncytium. SIP cells express a variety of receptors and ion channels, and conductance changes in any type of SIP cell affect the excitability and responses of the syncytium. SIP cells are known to provide pacemaker activity, propagation pathways for slow waves, transduction of inputs from motor neurons, and mechanosensitivity. Loss of interstitial cells has been associated with motor disorders of the gut. Interstitial cells are also found in a variety of other smooth muscles; however, in most cases, the physiological and pathophysiological roles for these cells have not been clearly defined. This review describes structural, functional, and molecular features of interstitial cells and discusses their contributions in determining the behaviors of smooth muscle tissues. PMID:24987007

Apocrine hidradenocarcinoma showing Paget's disease and mucinous metaplasia.

PubMed

Wahl, Carter E; Todd, Douglas H; Binder, Scott W; Cassarino, David S

2009-05-01

A 54-year-old man presented with a solitary, erythematous, rapidly growing 1-cm nodule on his scalp that had arisen over the previous 3 months. He had no history of skin cancer. An excisional biopsy of the lesion showed a fairly well-circumscribed but focally invasive tumor consisting of areas of typical-appearing clear cell hidradenoma as well as areas with mucinous goblet-type cells and cells with eosinophilic cytoplasm and decapitation-type secretion. There was marked cellular atypia, numerous atypical mitotic figures and focal necrosis. The tumor cells focally involved the overlying epidermis (Paget's disease). Large areas of mucin were identified throughout the lesion. The tumor cells stained with markers for cytokeratin 7 and focally for EMA and CEA, confirming ductal differentiation. The goblet cells and mucinous areas stained with mucicarmine and PASD. The patient was diagnosed with hidradenocarcinoma with mucinous differentiation. Associated Paget's disease has only rarely been reported, and mucinous metaplasia is a previously unreported feature in hidradenocarcinoma.

Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

PubMed Central

Mourad, Nathalie; Mounier, Nicolas; Brière, Josette; Raffoux, Emmanuel; Delmer, Alain; Feller, Alfred; Meijer, Chris J. L. M.; Emile, Jean-François; Bouabdallah, Réda; Bosly, André; Diebold, Jacques; Haioun, Corinne; Coiffier, Bertrand; Gisselbrecht, Christian

2008-01-01

To evaluate the prognostic significance of clinicobiologic and pathological features in angioimmunoblastic T-cell lymphoma (AITL), 157 AITL patients were retrieved from the GELA LNH87-LNH93 randomized clinical trials. One hundred forty-seven patients received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)–like regimen with intensified courses in half of them. Histologically, 41 cases were classified as “rich in large cells” and 116 as “classic” (including 19 rich in epithelioid cells, 14 rich in clear cells, and 4 with hyperplastic germinal centers). Sixty-two cases were scored for CD10 and CXCL13 expression according to the abundance of positive lymphoid cells. Median age was 62 years, with 81% advanced stage, 72% B symptoms, 65% anemia, 50% hypergammaglobulinemia, and 66% elevated LDH. Overall 7-year survival was 30%. In multivariate analysis, only male sex (P = .004), mediastinal lymphadenopathy (P = .041), and anemia (P = .042) adversely affected overall survival. Increase in large cells and high level of CD10 and CXCL13 did not affect survival. Intensive regimen did not improve survival. In conclusion, AITL is a morphologically heterogeneous T-cell lymphoma commonly expressing CXCL13 and CD10 and carrying few prognostic factors. It portends a poor prognosis even when treated intensively. However, AITL is not always lethal with 30% of patients alive at 7 years. PMID:18292286

The Effect of Anatomical Location of Lymph Node Metastases on Cancer Specific Survival in Patients with Clear Cell Renal Cell Carcinoma.

PubMed

Nini, Alessandro; Larcher, Alessandro; Cianflone, Francesco; Trevisani, Francesco; Terrone, Carlo; Volpe, Alessandro; Regis, Federica; Briganti, Alberto; Salonia, Andrea; Montorsi, Francesco; Bertini, Roberto; Capitanio, Umberto

2018-01-01

Positive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND). To describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM). The study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions. Descriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes. Median number of removed LN was 14 (IQR 9-19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI 95%: 1.3-3.9, p < 0.01) represented an independent predictor of CSM. When ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes. Lymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary kidney tumour, would aid patient risk stratification and multimodality upfront treatment.

Niches for the Long-Term Maintenance of Tissue-Resident Memory T Cells

PubMed Central

Takamura, Shiki

2018-01-01

Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection. CD4+ TRM cells typically localize below the epithelial layers, such as below the basement membrane, and cluster in lymphoid structures designed to optimize interactions with antigen-presenting cells upon reinfection. A key feature of TRM populations is their ability to be maintained in barrier tissues for prolonged periods of time. For example, skin CD8+ TRM cells displace epidermal niches originally occupied by γδ T cells, thereby enabling their stable persistence for years. It is also clear that the long-term maintenance of TRM cells in different microenvironments is dependent on multiple tissue-specific survival cues, although the specific details are poorly understood. However, not all TRM persist over the long term. Recently, we identified a new spatial niche for the maintenance of CD8+ TRM cells in the lung, which is created at the site of tissue regeneration after injury [termed repair-associated memory depots (RAMD)]. The short-lived nature of RAMD potentially explains the short lifespans of CD8+ TRM cells in this particular tissue. Clearly, a better understanding of the niche-dependent maintenance of TRM cells will be important for the development of vaccines designed to promote barrier immunity. In this review, we discuss recent advances in our understanding of the properties and nature of tissue-specific niches that maintain TRM cells in different tissues. PMID:29904388

Cytoplasmic expression of CD133 stemness marker is associated with tumor aggressiveness in clear cell renal cell carcinoma.

PubMed

Saeednejad Zanjani, Leili; Madjd, Zahra; Abolhasani, Maryam; Andersson, Yvonne; Rasti, Arezoo; Shariftabrizi, Ahmad; Asgari, Mojgan

2017-10-01

Prominin-1 (CD133) is one of the most commonly used markers for cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CSCs in renal cell carcinoma (RCC) remains unclear. The aim of this study was to investigate the expression patterns and prognostic significance of the cancer stem cell marker CD133 in different histological subtypes of RCC. CD133 expression was evaluated using immunohistochemistry in 193 well-defined renal tumor samples on tissue microarrays, including 136 (70.5%) clear cell renal cell carcinomas (CCRCCs), 26 (13.5%) papillary RCCs, and 31 (16.1%) chromophobe RCCs. The association between CD133 expression and clinicopathological features as well as the survival outcomes was determined. There was a statistically significant difference between CD133 expression among the different RCC subtypes. In CCRCC, higher cytoplasmic expression of CD133 was significantly associated with increase in grade, stage, microvascular invasion (MVI) and lymph node invasion (LNI), while no association was found with the membranous expression. Moreover, on multivariate analysis, TNM stage and nuclear grade were independent prognostic factors for overall survival (OS) in cytoplasmic expression. We showed that higher cytoplasmic CD133 expression was associated with more aggressive tumor behavior and more advanced disease in CCRCC but not in the other examined subtypes. Our results demonstrated that higher cytoplasmic CD133 expression is clinically significant in CCRCC and is associated with increased tumor aggressiveness and is useful for predicting cancer progression. Copyright © 2017 Elsevier Inc. All rights reserved.

PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

ClinicalTrials.gov

2017-08-23

VHL Gene Mutation; VHL; VHL Syndrome; VHL Gene Inactivation; Von Hippel; Von Hippel-Lindau Disease; Von Hippel's Disease; Von Hippel-Lindau Syndrome, Modifiers of; Clear Cell Renal Cell Carcinoma; Clear Cell RCC; ccRCC

Color edges extraction using statistical features and automatic threshold technique: application to the breast cancer cells.

PubMed

Ben Chaabane, Salim; Fnaiech, Farhat

2014-01-23

Color image segmentation has been so far applied in many areas; hence, recently many different techniques have been developed and proposed. In the medical imaging area, the image segmentation may be helpful to provide assistance to doctor in order to follow-up the disease of a certain patient from the breast cancer processed images. The main objective of this work is to rebuild and also to enhance each cell from the three component images provided by an input image. Indeed, from an initial segmentation obtained using the statistical features and histogram threshold techniques, the resulting segmentation may represent accurately the non complete and pasted cells and enhance them. This allows real help to doctors, and consequently, these cells become clear and easy to be counted. A novel method for color edges extraction based on statistical features and automatic threshold is presented. The traditional edge detector, based on the first and the second order neighborhood, describing the relationship between the current pixel and its neighbors, is extended to the statistical domain. Hence, color edges in an image are obtained by combining the statistical features and the automatic threshold techniques. Finally, on the obtained color edges with specific primitive color, a combination rule is used to integrate the edge results over the three color components. Breast cancer cell images were used to evaluate the performance of the proposed method both quantitatively and qualitatively. Hence, a visual and a numerical assessment based on the probability of correct classification (PC), the false classification (Pf), and the classification accuracy (Sens(%)) are presented and compared with existing techniques. The proposed method shows its superiority in the detection of points which really belong to the cells, and also the facility of counting the number of the processed cells. Computer simulations highlight that the proposed method substantially enhances the segmented image with smaller error rates better than other existing algorithms under the same settings (patterns and parameters). Moreover, it provides high classification accuracy, reaching the rate of 97.94%. Additionally, the segmentation method may be extended to other medical imaging types having similar properties.

The changing view of eukaryogenesis - fossils, cells, lineages and how they all come together.

PubMed

Dacks, Joel B; Field, Mark C; Buick, Roger; Eme, Laura; Gribaldo, Simonetta; Roger, Andrew J; Brochier-Armanet, Céline; Devos, Damien P

2016-10-15

Eukaryogenesis - the emergence of eukaryotic cells - represents a pivotal evolutionary event. With a fundamentally more complex cellular plan compared to prokaryotes, eukaryotes are major contributors to most aspects of life on Earth. For decades, we have understood that eukaryotic origins lie within both the Archaea domain and α-Proteobacteria. However, it is much less clear when, and from which precise ancestors, eukaryotes originated, or the order of emergence of distinctive eukaryotic cellular features. Many competing models for eukaryogenesis have been proposed, but until recently, the absence of discriminatory data meant that a consensus was elusive. Recent advances in paleogeology, phylogenetics, cell biology and microbial diversity, particularly the discovery of the 'Candidatus Lokiarcheaota' phylum, are now providing new insights into these aspects of eukaryogenesis. The new data have allowed the time frame during which eukaryogenesis occurred to be finessed, a more precise identification of the contributing lineages and the biological features of the contributors to be clarified. Considerable advances have now been used to pinpoint the prokaryotic origins of key eukaryotic cellular processes, such as intracellular compartmentalisation, with major implications for models of eukaryogenesis. © 2016. Published by The Company of Biologists Ltd.

Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

PubMed

Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

2018-05-01

Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[The characters and specific features of new human embryonic stem cells lines].

PubMed

Krylova, T A; Kol'tsova, A M; Zenin, V V; Gordeeva, O F; Musorina, A S; Goriachaia, T S; Shlykova, S A; Kamenetskaia, Iu K; Pinaev, G P; Polianskaia, G G

2009-01-01

Four continuous human embryonic stem cell lines (SC1, SC2, SC3 and SC4), derived from the blastocysts has been described. The cell lines were cultivated on mitotically inactivated human feeder cells. The cell lines SC1 and SC2 have passed through 150 population doublings and the cell lines SC3 and SC4 -- near 120 populations doublings, which exceeds Hayflick limit sufficiently. These cell lines maintain high activity of alkaline phosphatase, expression of transcription factor OCT-4 and cell surface antigens (SSEA-4, TRA-1-60 and TRA-1-81), confirming their ESC status and human specificity. Immunofluorescent detection of antigens, characteristic of ectoderm, endoderm and mesoderm confirms the ability of these cells to retain their pluripotency under in vitro condition. PCR analysis revealed expression of six genes specific for pluripotent cells (OCT-4, NANOG, DPPA3/STELLA, TDGF/CRIPTO and LEFTYA). Correlation between the level of proliferative activity and the character of DNA-bound fluorescent staining was found. Fluorescent dyes, Hoechst 33342 and PI, produced diffuse staining of the nuclei in slowly proliferating cells of the SC1 and SC2 lines. In contrast, in actively proliferating cells of the SC3 and SC4 lines, the clear staining of the nuclei was observed. Upon changing the cultivation condition, proliferative activity of SC3 and SC4 lines decreased and became similar to that of SC1 and SC2 lines. The character of the fluorescent staining of all these lines was also shown to be similar. These results show that quality of the fluorescent staining with Hoechst 33342 and PI reflects the level of proliferation. Possible causes and mechanisms of this feature of human ESC are discussed.

Characterization of histological subtypes of clear cell renal cell carcinoma using contrast-enhanced ultrasound (CEUS).

PubMed

Reimann, R; Rübenthaler, J; Hristova, P; Staehler, M; Reiser, M; Clevert, D A

2015-10-16

The aim of this study was to analyze the histological subtypes of clear cell renal cell carcinoma (RCC) examined by means of contrast-enhanced ultrasound (CEUS) and a second generation blood pool agent (SonoVue®, Bracco, Milan, Italy) during the pre-operative phase. 29 patients with histologically proven subtypes of clear cell RCC were examined. A total of three patients were diagnosed with highly differentiated clear cell RCC, 21 out of 29 cases with moderately differentiated clear cell RCC and five out of 29 patients had insufficiently differentiated clear cell RCC. An experienced radiologist examined the patients with CEUS. The following parameters were analyzed: maximum signal intensity (PEAK), time elapsed until PEAK is reached (MTT), local blood flow (RBF), area under the time intensity curve (AUC) and the signal intensity (SI) during the course of time. For the groups all comparisons are made based on healthy renal parenchyma. In the clear cell RCC significant differences (significance level p < 0.05) between cancerous tissue and the healthy renal parenchyma were noticed in all four parameters. Therefore, the clear cell RCC stands out due to its reduced blood volume. However, it reached the PEAK reading relatively rapidly and its signal intensity was always lower than that of the healthy renal parenchyma. In the arterial phase retarded absorption of the contrast agent was observed, followed by fast washing out of the contrast agent bubbles.In all three histological subgroups no significant differences were noticed in PEAK and SI. However, the diagrams showed the possible bias, that the group of the insufficiently differentiated clear cell RCC had the highest PEAK-value and the highest signal intensity when compared with highly and moderately differentiated clear cell RCC. Our study suggests that CEUS may be an additional tool for non-invasive characterisation and differentiation of the three histological subtypes of clear cell RCC. Furthermore, it seems to have an additional diagnostic value in daily clinical.

Clear cell hepatocellular carcinoma: Back to the basics for diagnosis.

PubMed

Sakhuja, Puja; Mishra, Pramod K; Rajesh, R; Sharma, Ashok Kumar; Gondal, Ranjana; Singh, Meeta

2015-01-01

Hepatocellular carcinoma (HCC) is a common cancer world-wide with a higher incidence in Asia. Clear cell variant of HCC (CCHCC) has a frequency ranging from 0.4% to 37%. The presence of 90-100% clear cells is rare. In the present case, a 35-year-old female patient presented with fever and a large abdominal mass in the right hypochondrium. Histology of the tumor revealed >95% clear cells and after taking multiple sections from different areas of tumor only few scattered cells with eosinophilic cytoplasm were found. Immunohistochemistry with Hep Par 1, Glypican 3 and polyclonal carcinoembryonic antigen were negative as were all other markers for metastatic clear cell tumors. Histological diagnosis was based on routine H and E sections showing a histological pattern of architecture with thickened trabeculae. We describe a rare case of CCHCC with >95% clear cells and no immunoreactivity in tumor cells in a non-cirrhotic liver.

Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

PubMed

Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Poly-N-Acetylglucosamine Production by Staphylococcus epidermidis Cells Increases Their In Vivo Proinflammatory Effect

PubMed Central

Ferreirinha, Pedro; Pérez-Cabezas, Begoña; Correia, Alexandra; Miyazawa, Bruna; França, Angela; Carvalhais, Virgínia; Faustino, Augusto; Cordeiro-da-Silva, Anabela; Teixeira, Luzia; Pier, Gerald B.

2016-01-01

Poly-N-acetylglucosamine (PNAG) is a major component of the Staphylococcus epidermidis biofilm extracellular matrix. However, it is not yet clear how this polysaccharide impacts the host immune response and infection-associated pathology. Faster neutrophil recruitment and bacterial clearance were observed in mice challenged intraperitoneally with S. epidermidis biofilm cells of the PNAG-producing 9142 strain than in mice similarly challenged with the isogenic PNAG-defective M10 mutant. Moreover, intraperitoneal priming with 9142 cells exacerbated liver inflammatory pathology induced by a subsequent intravenous S. epidermidis challenge, compared to priming with M10 cells. The 9142-primed mice had elevated splenic CD4+ T cells producing gamma interferon and interleukin-17A, indicating that PNAG promoted cell-mediated immunity. Curiously, despite having more marked liver tissue pathology, 9142-primed mice also had splenic T regulatory cells with greater suppressive activity than those of their M10-primed counterparts. By showing that PNAG production by S. epidermidis biofilm cells exacerbates host inflammatory pathology, these results together suggest that this polysaccharide contributes to the clinical features associated with biofilm-derived infections. PMID:27481237

DUX4 Immunohistochemistry Is a Highly Sensitive and Specific Marker for CIC-DUX4 Fusion-positive Round Cell Tumor.

PubMed

Siegele, Bradford; Roberts, Jon; Black, Jennifer O; Rudzinski, Erin; Vargas, Sara O; Galambos, Csaba

2017-03-01

The histologic differential diagnosis of pediatric and adult round cell tumors is vast and includes the recently recognized entity CIC-DUX4 fusion-positive round cell tumor. The diagnosis of CIC-DUX4 tumor can be suggested by light microscopic and immunohistochemical features, but currently, definitive diagnosis requires ancillary genetic testing such as conventional karyotyping, fluorescence in situ hybridization, or molecular methods. We sought to determine whether DUX4 expression would serve as a fusion-specific immunohistochemical marker distinguishing CIC-DUX4 tumor from potential histologic mimics. A cohort of CIC-DUX4 fusion-positive round cell tumors harboring t(4;19)(q35;q13) and t(10;19)(q26;q13) translocations was designed, with additional inclusion of a case with a translocation confirmed to involve the CIC gene without delineation of the partner. Round cell tumors with potentially overlapping histologic features were also collected. Staining with a monoclonal antibody raised against the C-terminus of the DUX4 protein was applied to all cases. DUX4 immunohistochemistry exhibited diffuse, crisp, strong nuclear staining in all CIC-DUX4 fusion-positive round cell tumors (5/5, 100% sensitivity), and exhibited negative staining in nuclei of all of the other tested round cell tumors, including 20 Ewing sarcomas, 1 Ewing-like sarcoma, 11 alveolar rhabdomyosarcomas, 9 embryonal rhabdomyosarcomas, 12 synovial sarcomas, 7 desmoplastic small round cell tumors, 3 malignant rhabdoid tumors, 9 neuroblastomas, and 4 clear cell sarcomas (0/76, 100% specificity). Thus, in our experience, DUX4 immunostaining distinguishes CIC-DUX4 tumors from other round cell mimics. We recommend its use when CIC-DUX4 fusion-positive round cell tumor enters the histologic differential diagnosis.

Many Specialists for Suppressing Cortical Excitation

PubMed Central

Burkhalter, Andreas

2008-01-01

Cortical computations are critically dependent on GABA-releasing neurons for dynamically balancing excitation with inhibition that is proportional to the overall level of activity. Although it is widely accepted that there are multiple types of interneurons, defining their identities based on qualitative descriptions of morphological, molecular and physiological features has failed to produce a universally accepted ‘parts list’, which is needed to understand the roles that interneurons play in cortical processing. A list of features has been published by the Petilla Interneurons Nomenclature Group, which represents an important step toward an unbiased classification of interneurons. To this end some essential features have recently been studied quantitatively and their association was examined using multidimensional cluster analyses. These studies revealed at least 3 distinct electrophysiological, 6 morphological and 15 molecular phenotypes. This is a conservative estimate of the number of interneuron types, which almost certainly will be revised as more quantitative studies will be performed and similarities will be defined objectively. It is clear that interneurons are organized with physiological attributes representing the most general, molecular characteristics the most detailed and morphological features occupying the middle ground. By themselves, none of these features are sufficient to define classes of interneurons. The challenge will be to determine which features belong together and how cell type-specific feature combinations are genetically specified. PMID:19225588

Malignant perivascular epithelioid cell tumor of the orbit: Report of a case and review of literature.

PubMed

Alam, Md Shahid; Mukherjee, Bipasha; Krishnakumar, S; Biswas, Jyotirmay

2017-09-01

Perivascular epithelioid cell tumor (PEComa) is a rare neoplasm considered to arise from myomelanocytic cell lineage. The uterus is reportedly the most common site to be involved. Orbital PEComa is extremely rare with only two cases reported till date. A 5-year-old male presented with a right medial orbital mass for the last 6 months. The patient was diagnosed with alveolar soft part sarcoma elsewhere. Magnetic resonance imaging features were suggestive of lymphangioma with bleeding. The excision biopsy revealed multiple tumor cells comprising epithelioid cells with clear cytoplasm, along with nuclear atypia and mitosis. Immunohistochemistry was positive for HMB-45, smooth muscle actin, vimentin, and CD-34. It was negative for cytokeratin, S-100, and synaptophysin, which clinched the diagnosis of malignant orbital PEComa. Neoadjuvant chemotherapy was administered. There was no recurrence at 24 months of follow-up. At present, there is no consensus on management protocol for malignant PEComa. Complete surgical excision with chemotherapy appears to offer the best prognosis.

Malignant perivascular epithelioid cell tumor of the orbit: Report of a case and review of literature

PubMed Central

Alam, Md. Shahid; Mukherjee, Bipasha; Krishnakumar, S; Biswas, Jyotirmay

2017-01-01

Perivascular epithelioid cell tumor (PEComa) is a rare neoplasm considered to arise from myomelanocytic cell lineage. The uterus is reportedly the most common site to be involved. Orbital PEComa is extremely rare with only two cases reported till date. A 5-year-old male presented with a right medial orbital mass for the last 6 months. The patient was diagnosed with alveolar soft part sarcoma elsewhere. Magnetic resonance imaging features were suggestive of lymphangioma with bleeding. The excision biopsy revealed multiple tumor cells comprising epithelioid cells with clear cytoplasm, along with nuclear atypia and mitosis. Immunohistochemistry was positive for HMB-45, smooth muscle actin, vimentin, and CD-34. It was negative for cytokeratin, S-100, and synaptophysin, which clinched the diagnosis of malignant orbital PEComa. Neoadjuvant chemotherapy was administered. There was no recurrence at 24 months of follow-up. At present, there is no consensus on management protocol for malignant PEComa. Complete surgical excision with chemotherapy appears to offer the best prognosis. PMID:28905842

Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin.

PubMed

Federici, Cristina; Petrucci, Francesco; Caimi, Stefano; Cesolini, Albino; Logozzi, Mariantonia; Borghi, Martina; D'Ilio, Sonia; Lugini, Luana; Violante, Nicola; Azzarito, Tommaso; Majorani, Costanza; Brambilla, Daria; Fais, Stefano

2014-01-01

Intrinsic resistance to cytotoxic drugs has been a main issue in cancer therapy for decades. Microenvironmental acidity is a simple while highly efficient mechanism of chemoresistance, exploited through impairment of drug delivery. The latter is achieved by extracellular protonation and/or sequestration into acidic vesicles. This study investigates the importance of extracellular acidosis and nanovesicle (exosome) release in the resistance of human tumour cell to cisplatin (CisPt); in parallel to proton pump inhibitors (PPI) ability of interfering with these tumour cell features. The results showed that CisPt uptake by human tumour cells was markedly impaired by low pH conditions. Moreover, exosomes purified from supernatants of these cell cultures contained various amounts of CisPt, which correlated to the pH conditions of the culture medium. HPLC-Q-ICP-MS analysis revealed that exosome purified from tumour cell culture supernatants contained CisPt in its native form. PPI pre-treatment increased cellular uptake of CisPt, as compared to untreated cells, in an acidic-depend manner. Furthermore, it induced a clear inhibition of exosome release by tumour cells. Human tumours obtained from xenografts pretreated with PPI contained more CisPt as compared to tumours from xenografts treated with CisPt alone. Further analysis showed that in vivo PPI treatment induced a clear reduction in the plasmatic levels of tumour-derived exosomes which also contained lower level of CisPt. Altogether, these findings point to the identification of a double mechanism that human malignant melanoma use in resisting to a dreadful cellular poison such as cisplatin. This framework of resistance includes both low pH-dependent extracellular sequestration and an exosome-mediated elimination. Both mechanisms are markedly impaired by proton pump inhibition, leading to an increased CisPt-dependent cytotoxicity.

Exosome Release and Low pH Belong to a Framework of Resistance of Human Melanoma Cells to Cisplatin

PubMed Central

Federici, Cristina; Petrucci, Francesco; Caimi, Stefano; Cesolini, Albino; Logozzi, Mariantonia; Borghi, Martina; D'Ilio, Sonia; Lugini, Luana; Violante, Nicola; Azzarito, Tommaso; Majorani, Costanza; Brambilla, Daria; Fais, Stefano

2014-01-01

Intrinsic resistance to cytotoxic drugs has been a main issue in cancer therapy for decades. Microenvironmental acidity is a simple while highly efficient mechanism of chemoresistance, exploited through impairment of drug delivery. The latter is achieved by extracellular protonation and/or sequestration into acidic vesicles. This study investigates the importance of extracellular acidosis and nanovesicle (exosome) release in the resistance of human tumour cell to cisplatin (CisPt); in parallel to proton pump inhibitors (PPI) ability of interfering with these tumour cell features. The results showed that CisPt uptake by human tumour cells was markedly impaired by low pH conditions. Moreover, exosomes purified from supernatants of these cell cultures contained various amounts of CisPt, which correlated to the pH conditions of the culture medium. HPLC-Q-ICP-MS analysis revealed that exosome purified from tumour cell culture supernatants contained CisPt in its native form. PPI pre-treatment increased cellular uptake of CisPt, as compared to untreated cells, in an acidic-depend manner. Furthermore, it induced a clear inhibition of exosome release by tumour cells. Human tumours obtained from xenografts pretreated with PPI contained more CisPt as compared to tumours from xenografts treated with CisPt alone. Further analysis showed that in vivo PPI treatment induced a clear reduction in the plasmatic levels of tumour-derived exosomes which also contained lower level of CisPt. Altogether, these findings point to the identification of a double mechanism that human malignant melanoma use in resisting to a dreadful cellular poison such as cisplatin. This framework of resistance includes both low pH-dependent extracellular sequestration and an exosome-mediated elimination. Both mechanisms are markedly impaired by proton pump inhibition, leading to an increased CisPt-dependent cytotoxicity. PMID:24516610

Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

PubMed

Lalani, Aly-Khan A; Gray, Kathryn P; Albiges, Laurence; Callea, Marcella; Pignon, Jean-Christophe; Pal, Soumitro; Gupta, Mamta; Bhatt, Rupal S; McDermott, David F; Atkins, Michael B; Woude, G F Vande; Harshman, Lauren C; Choueiri, Toni K; Signoretti, Sabina

2017-11-28

In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma

PubMed Central

Gatto, Francesco; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Several common oncogenic pathways have been implicated in the emergence of renowned metabolic features in cancer, which in turn are deemed essential for cancer proliferation and survival. However, the extent to which different cancers coordinate their metabolism to meet these requirements is largely unexplored. Here we show that even in the heterogeneity of metabolic regulation a distinct signature encompassed most cancers. On the other hand, clear cell renal cell carcinoma (ccRCC) strongly deviated in terms of metabolic gene expression changes, showing widespread down-regulation. We observed a metabolic shift that associates differential regulation of enzymes in one-carbon metabolism with high tumor stage and poor clinical outcome. A significant yet limited set of metabolic genes that explained the partial divergence of ccRCC metabolism correlated with loss of von Hippel-Lindau tumor suppressor (VHL) and a potential activation of signal transducer and activator of transcription 1. Further network-dependent analyses revealed unique defects in nucleotide, one-carbon, and glycerophospholipid metabolism at the transcript and protein level, which contrasts findings in other tumors. Notably, this behavior is recapitulated by recurrent loss of heterozygosity in multiple metabolic genes adjacent to VHL. This study therefore shows how loss of heterozygosity, hallmarked by VHL deletion in ccRCC, may uniquely shape tumor metabolism. PMID:24550497

Isodicentric Y mosaicism involving a 46, XX cell line: Implications for management.

PubMed

Hipp, Lauren E; Mohnach, Lauren H; Wei, Sainan; Thomas, Inas H; Elhassan, Maha E; Sandberg, David E; Quint, Elisabeth H; Keegan, Catherine E

2016-01-01

Carriers of isodicentric Y (idicY) mosaicism exhibit a wide range of clinical features, including short stature, gonadal abnormalities, and external genital anomalies. However, the phenotypic spectrum for individuals carrying an idicY and a 46, XX cell line is less clearly defined. A more complete description of the phenotype related to idicY is thus essential to guide management related to pubertal development, fertility, and gonadoblastoma risk in mosaic carriers. Findings from the evaluation of twin females with an abnormal karyotype, 48, XX, +idic(Yq) x2/47, XX, +idic(Yq)/46, XX, are presented to highlight the importance of interdisciplinary care in the management of multifaceted disorders of sex development. © 2015 Wiley Periodicals, Inc.

Targeting the SASP to combat ageing: Mitochondria as possible intracellular allies?

PubMed

Birch, Jodie; Passos, João F

2017-05-01

Anti-senescence therapies, such as drugs that specifically kill senescent cells, to stave off ageing are currently under investigation. While these interventions show promise, their potential pitfalls are discussed herein. We have shown that the mitochondria are essential for development of senescence and many of the associated phenotypes, including the often detrimental senescence-associated secretory phenotype (SASP). Here, we disentangle many ways in which the mitochondria may influence senescence and development of the SASP and focus on possible pathways that could be exploited for future generation of anti-senescence therapies with a clear aim; to specifically eliminate the problematic features of senescent cells, while maintaining their beneficial characteristics. © 2017 The Authors. BioEssays Published by WILEY Periodicals, Inc.

Melanotic Xp11 translocation renal cancer: report of a case with a unique intratumoral sarcoid-like reaction.

PubMed

Ritterhouse, Lauren L; Cykowski, Matthew D; Hassell, Lewis A; Slobodov, Gennady; Bane, Barbara L

2014-04-15

Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature. Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year-old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy. This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping features between Xp11 translocation renal cell carcinoma, melanoma, and perivascular epithelioid cell neoplasms. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7225796341180634.

A requirement for the Vgamma1+ subset of peripheral gammadelta T cells in the control of the systemic growth of Toxoplasma gondii and infection-induced pathology.

PubMed

Egan, Charlotte E; Dalton, Jane E; Andrew, Elizabeth M; Smith, Judith E; Gubbels, Marc-Jan; Striepen, Boris; Carding, Simon R

2005-12-15

gammadelta T cells are a diverse population of T cells that are widely distributed and are a common feature of pathogen-induced immune responses. It is not clear, however, whether different populations of gammadelta T cells have specific functions, and what factors determine the functional properties of individual populations. A murine model of peroral Toxoplasma gondii infection was used to determine the contribution Vgamma1+ intestinal intraepithelial lymphocytes (IELs) vs systemic Vgamma1+ T cells make to the acute and chronic stages of the host immune response, and whether the macrophage cytocidal activity of Vgamma1+ T cells described in bacterial infections is seen in other, unrelated infectious disease models. In response to oral infection with virulent type 1 or avirulent type II strains of T. gondii, TCR-delta-/- mice rapidly developed severe ileitis. In contrast, in mice deficient in Vgamma1+ T cells and IELs and wild-type mice, inflammation was delayed in onset and less severe. The protective effect of (Vgamma1-) IELs to Toxoplasma infection was unrelated to their cytolytic and cytokine (Th1)-producing capabilities. Systemic Vgamma1+ T cells were shown to play an essential role in limiting parasite growth and inflammation in peripheral tissues and, in particular, in the CNS, that was associated with their ability to efficiently kill parasite-elicited and infected macrophages. These findings suggest that macrophage cytocidal activity of Vgamma1+ T cells may be a universal feature of pathogen-induced immune responses and that microenvironmental factors influence the involvement and function of gammadelta T cells in the host response to infection.

Chromatin remodeling and stem cell theory of relativity.

PubMed

Cerny, Jan; Quesenberry, Peter J

2004-10-01

The field of stem cell biology is currently being redefined. Stem cell (hematopoietic and non-hematopoietic) differentiation has been considered hierarchical in nature, but recent data suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. The stem cell (hematopoietic and non-hematopoietic) phenotype, the total differentiation capacity (hematopoietic and non-hematopoietic), gene expression as well as other stem cell functional characteristics (homing, receptor and adhesion molecule expression) vary throughout a cell-cycle transit widely. This seems to be dependent on shifting chromatin and gene expression with cell-cycle transit. The published data on DNA methylation, histone acetylation, and also RNAi, the major regulators of gene expression, conjoins very well and provides an explanation for the major issues of stem cell biology. Those features of stem cells mentioned above can be rather difficult to apprehend when a classical hierarchy biology view is applied, but they become clear and easier to understand once they are correlated with the underlining epigenetic changes. We are entering a new era of stem cell biology the era of "chromatinomics." We are one step closer to the practical use of cellular therapy for degenerative diseases.

Investigating the limits of filopodial sensing: a brief report using SEM to image the interaction between 10 nm high nano-topography and fibroblast filopodia.

PubMed

Dalby, M J; Riehle, M O; Johnstone, H; Affrossman, S; Curtis, A S G

2004-01-01

Having the ability to control cell behaviour would be of great advantage in tissue engineering. One method of gaining control over cell adhesion, proliferation, guidance and differentiation is use of topography. Whilst it has be known for some time that cells can be guided by micro-topography, it is only recently becoming clear that cells will respond strongly to nano-scale topography. The fact that cells will take cues from their micro- and nano-environment suggests that the cells are in some way 'spatially aware'. It is likely that cells probe the shape of their surroundings using filopodia, and that this initial filopodia/topography interaction may be critical to down-stream cell reactions to biomaterials, or indeed, the extracellular matrix. One intriguing question is how small a feature can cells sense? In order to investigate the limits of cell sensing, high-resolution scanning electron microscopy has been used to simultaneously view cell filopodia and 10 nm high nano-islands. Fluorescence microscopy has also been used to look at adhesion formation. The results showed distinct filopodial/nano-island interaction and changes in adhesion morphology.

Delayed xenograft rejection.

PubMed

Hancock, W W

1997-01-01

The triumph of genetic engineering in overcoming hyperacute rejection (HAR) of a discordant organ xenograft is clear, but the promise of clinical application of xenotransplantation remains unfulfilled as further immunologic barriers are defined that lead to rejection of a vascularized xenograft within days of transplantation. This report describes the features of this second set of immunologic responses, collectively termed delayed xenograft rejection (DXR). DXR is a syndrome seen in xenograft recipients in which HAR has been avoided or suppressed by antibody depletion or blockade of complement activation. DXR may result, at least in part, from the persisting activation of those pathways first encountered during the HAR phase. Serial studies over several days after transplant show that, histologically, xenografts undergoing DXR demonstrate varying combinations of (1) progressive infiltration by activated macrophages and natural killer (NK) cells, (2) platelet aggregation and fibrin deposition throughout the microvasculature, and (3) endothelial activation. In various experimental models, DXR is T cell-independent and can occur in the absence of demonstrable xenoreactive antibodies. Hence DXR is probably best regarded as arising from the activation of innate host defense mechanisms coupled with failure of normal regulatory mechanisms due to manifold molecular incompatibilities. Although DXR-like features can be seen in concordant models, T cell involvement in the latter is probably requisite. Similarly, in a much muted form, aspects of a DXR-like process may contribute to numerous inflammatory processes, including allograft rejection. The importance of DXR in xenotransplantation is that its development appears resistant to all but the most dense and toxic forms of immunosuppression, which prolong xenograft survival at the expense of inducing host leukopenia, thrombocytopenia, and coagulopathies. It is likely that until the basis of DXR is more clearly understood there can be no further significant progress toward clinical xenotransplantation. However, as the mechanisms responsible for DXR are dissected and understood, still further genetic engineering of donor pigs, involving the introduction of additional or multiple genes to regulate macrophage and NK cell responses, local coagulation, and endothelial cell activation, may once again prove to be an attractive, practical, powerful therapeutic option.

Balloon cell nevus of the iris.

PubMed

Morcos, Mohib W; Odashiro, Alexandre; Bazin, Richard; Pereira, Patricia Rusa; O'Meara, Aisling; Burnier, Miguel N

2014-12-01

Balloon cell nevus is a rare histopathological lesion characterized by a predominance of large, vesicular and clear cells, called balloon cells. There is only 1 case of balloon cell nevus of the iris reported in the literature. A 55 year-old man presented a pigmented elevated lesion in the right iris since the age of 12 years old. The lesion had been growing for the past 2 years and excision was performed. Histopathological examination showed a balloon cell nevus composed of clear and vacuolated cells without atypia. A typical spindle cell nevus of the iris was also observed. The differential diagnosis included xanthomatous lesions, brown adipocyte or other adipocytic lesions, clear cell hidradenoma, metastatic clear cell carcinoma of the kidney and clear cell sarcoma. The tumor was positive for Melan A, S100 protein and HMB45. Balloon cell nevus of the iris is rare but should be considered in the differential diagnosis of melanocytic lesions of the iris. Copyright © 2014 Elsevier GmbH. All rights reserved.

Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.

PubMed

Zhang, Yu-Dong; Wu, Chen-Jiang; Wang, Qing; Zhang, Jing; Wang, Xiao-Ning; Liu, Xi-Sheng; Shi, Hai-Bin

2015-08-01

The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC). Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions. Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p < 0.05). High-grade clear cell RCC had significantly lower mean, median, and 10th percentile ADCs but higher inhomogeneity and median R2* than low-grade clear cell RCC (all p < 0.05). Compared with other histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p < 0.05) and larger hemorrhagic area than low-grade clear cell RCC (high-grade, 34.9% ± 31.6%; low-grade, 8.9 ± 16.8%; p < 0.05). A close relation was found between MRI indexes and pathologic findings. Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

Ultra structural changes occurring in duct ectasia and periductal mastitis and their significance in etiopathogenesis.

PubMed

Ramalingam, Kirithiga; Vuthaluru, Seenu; Srivastava, Anurag; Dinda, Amit Kumar; Dhar, Anita

2017-01-01

Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study.

Ultra structural changes occurring in duct ectasia and periductal mastitis and their significance in etiopathogenesis

PubMed Central

Ramalingam, Kirithiga; Vuthaluru, Seenu; Srivastava, Anurag; Dinda, Amit Kumar; Dhar, Anita

2017-01-01

Introduction Duct ectasia (DE) and periductal mastitis (PDM) are the most common benign breast conditions seen in women. The etiopathogenesis of these entities is still not clear and most of the theories regarding the causation are based on the histological features as seen on light microscopy. The ultramicroscopic features associated with these conditions that may give more insight to the etiopathogenesis are unknown. Aim To study the ultrastructural changes occurring in mammary duct cones in patients with DE and PDM using Transmission Electron Microscopic (TEM). Method Major ducts removed by radical duct excision from 21 patients with final histopathological diagnosis of DE and PDM were subjected to TEM study with 2 normal duct samples as controls. Results The TEM features of DE were denudation of the epithelial cells with focal loss of microvilli, widening of the inter-epithelial junctions with focal disruption of the T bars, periductal collagenisation without inflammation, and features suggestive of Epithelial Mesenchymal Transition (EMT). PDM features are intact epithelial lining with proliferative epithelium and periductal collagenisation with inflammation. Conclusions Based on the TEM findings, we suggest that DE and PDM are two different entities. EMT a novel finding observed in DE in this study. PMID:28273122

Human immunophenotyping via low-variance, low-bias, interpretive regression modeling of small, wide data sets: Application to aging and immune response to influenza vaccination.

PubMed

Holmes, Tyson H; He, Xiao-Song

2016-10-01

Small, wide data sets are commonplace in human immunophenotyping research. As defined here, a small, wide data set is constructed by sampling a small to modest quantity n,1

Human Immunophenotyping via Low-Variance, Low-Bias, Interpretive Regression Modeling of Small, Wide Data Sets: Application to Aging and Immune Response to Influenza Vaccination

PubMed Central

Holmes, Tyson H.; He, Xiao-Song

2016-01-01

Small, wide data sets are commonplace in human immunophenotyping research. As defined here, a small, wide data set is constructed by sampling a small to modest quantity n, 1 < n < 50, of human participants for the purpose of estimating many parameters p, such that n < p < 1,000. We offer a set of prescriptions that are designed to facilitate low-variance (i.e. stable), low-bias, interpretive regression modeling of small, wide data sets. These prescriptions are distinctive in their especially heavy emphasis on minimizing use of out-of-sample information for conducting statistical inference. That allows the working immunologist to proceed without being encumbered by imposed and often untestable statistical assumptions. Problems of unmeasured confounders, confidence-interval coverage, feature selection, and shrinkage/denoising are defined clearly and treated in detail. We propose an extension of an existing nonparametric technique for improved small-sample confidence-interval tail coverage from the univariate case (single immune feature) to the multivariate (many, possibly correlated immune features). An important role for derived features in the immunological interpretation of regression analyses is stressed. Areas of further research are discussed. Presented principles and methods are illustrated through application to a small, wide data set of adults spanning a wide range in ages and multiple immunophenotypes that were assayed before and after immunization with inactivated influenza vaccine (IIV). Our regression modeling prescriptions identify some potentially important topics for future immunological research. 1) Immunologists may wish to distinguish age-related differences in immune features from changes in immune features caused by aging. 2) A form of the bootstrap that employs linear extrapolation may prove to be an invaluable analytic tool because it allows the working immunologist to obtain accurate estimates of the stability of immune parameter estimates with a bare minimum of imposed assumptions. 3) Liberal inclusion of immune features in phenotyping panels can facilitate accurate separation of biological signal of interest from noise. In addition, through a combination of denoising and potentially improved confidence interval coverage, we identify some candidate immune correlates (frequency of cell subset and concentration of cytokine) with B cell response as measured by quantity of IIV-specific IgA antibody-secreting cells and quantity of IIV-specific IgG antibody-secreting cells. PMID:27196789

Continuous hematopoietic cell lines as model systems for leukemia-lymphoma research.

PubMed

Drexler, H G; Matsuo, A Y; MacLeod, R A

2000-11-01

Along with other improvements, the advent of continuous human leukemia-lymphoma (LL) cell lines as a rich resource of abundant, accessible and manipulable living cells has contributed significantly to a better understanding of the pathophysiology of hematopoietic tumors. The first LL cell lines, Burkitt's lymphoma-derived lines, were established in 1963. Since then, more than 1000 cell lines have been described, although not all of them in full detail. The major advantages of continuous cell lines is the unlimited supply and worldwide availability of identical cell material, and the infinite viable storability in liquid nitrogen. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro under preservation of most cellular features, and specific genetic alterations. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines must be discerned from Epstein-Barr virus (EBV)-immortalized normal cells, using various distinguishing parameters. However, the picture is not quite so straightforward, as some types of LL cell lines are indeed EBV+, and some EBV+ normal cell lines carry also genetic aberrations and may mimic malignancy-associated features. Apart from EBV and human T-cell leukemia virus in some lines, the majority of wild-type LL cell lines are virus-negative. The efficiency of cell line establishment is rather low and the deliberate establishment of new LL cell lines remains by and large an unpredictable random process. Difficulties in establishing continuous cell lines may be caused by the inappropriate selection of nutrients and growth factors for these cells. Clearly, a generally suitable microenvironment for hematopoietic cells, either malignant or normal, cannot yet be created in vitro. The characterization and publication of new LL cell lines should provide important and informative core data, attesting to their scientific significance. Large percentages of LL cell lines are contaminated with mycoplasma (about 30%) or are cross-contaminated with other cell lines (about 15-20%). Solutions to these problems are sensitive detection, effective elimination and rigorous prevention of mycoplasma infection, and proper, regular authentication of cell lines. The underlying cause, however, appears to be negligent cell culture practice. The willingness of investigators to make their LL cell lines available to others is all too often limited. There is a need in the scientific community for clean and authenticated high-quality LL cell lines to which every scientist has access. These are offered by various institutionalized public cell line banks. It has been argued that LL cell lines are genetically unstable (both cytogenetically and molecular genetically). For instance, cell lines are supposed to acquire numerical and structural chromosomal alterations and various types of mutations (e.g. point mutations) in vitro. We present evidence that while nearly 100% of all LL cell lines indeed carry genetic alterations, these alterations appear to be stable rather than unstable. As an example of the practical utility of LL cell lines, the recent advances in studies of classical and molecular cytogenetics, which in large part were made possible by cell lines, are highlighted. A list of the most useful, robust and publicly available reference cell lines that may be used for a variety of experimental purposes is proposed. Clearly, by opening new avenues for investigation, studies of LL cell lines have provided seminal insights into the biology of hematopoietic neoplasia. Over a period of nearly four decades, these initially rather exotic cell cultures, known only to a few specialists, have become ubiquitous powerful research tools that are available to every investigator.

Primary non-clear-cell adenocarcinoma of the vagina in a diethylstilbestrol exposed woman.

PubMed

Patel, Samit A; Sunde, Jan

2014-04-01

A 54-year-old woman with a history of in-utero diethylstilbestrol (DES) exposure, who had a prior hysterectomy for symptomatic leiomyomata and dysmenorrhea, presented for vaginal bleeding. Vaginal biopsies showed a non-clear-cell adenocarcinoma, and the patient was subsequently treated with radiation therapy. We present a case of primary vaginal non-clear-cell adenocarcinoma in a patient with in-utero DES exposure. Continued monitoring of older DES-exposed women for vaginal lesions is warranted because of reported cases of non-clear-cell adenocarcinoma and persistent risk of clear cell adenocarcinoma. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

High-dose interleukin 2 in patients with metastatic renal cell carcinoma with sarcomatoid features

PubMed Central

Arjunan, Ananth; Wang, Hong; Saul, Melissa; Davar, Diwakar; Appleman, Leonard J.; Friedland, David; Parikh, Rahul A.

2017-01-01

Background High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12–20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10–15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Methods Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer′s exact test and Wilcoxon rank sum test. Results Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0–21.3). Median OS was 30.5 months (95% CI 13.3–57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3–35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4–10.2). Conclusion In patients with mRCC with sarcomatoid features, use of HD IL-2 was associated with a modest ORR and a higher survival compared to historical controls (patients with mRCC and sarcomatoid features). Thus, HD IL-2 may have a role in treating selected patients with mRCC with sarcomatoid features. PMID:29261796

High-dose interleukin 2 in patients with metastatic renal cell carcinoma with sarcomatoid features.

PubMed

Achkar, Tala; Arjunan, Ananth; Wang, Hong; Saul, Melissa; Davar, Diwakar; Appleman, Leonard J; Friedland, David; Parikh, Rahul A

2017-01-01

High-dose interleukin-2 (HD IL-2) is used in the treatment of metastatic renal cell carcinoma (mRCC) and has an overall response rate (ORR) of 12-20% and a complete response rate (CR) of 8% in unselected populations with predominantly clear cell type renal cell carcinoma. Nearly 10-15% of patients with renal cell carcinoma exhibit sarcomatoid differentiation, a feature which correlates with a median overall survival (OS) of 9 months and overall poor prognosis. We report a single institution experience with 21 patients with mRCC with sarcomatoid features post-nephrectomy who were treated with HD IL-2. Twenty one patients with mRCC with sarcomatoid features post-nephrectomy who underwent therapy with HD IL-2 were identified at the University of Pittsburgh Medical Center from 2004 to 2016. Baseline patient characteristics, HD IL-2 cycles, time to progression, and subsequent therapies were evaluated. OS and progression-free survival (PFS) in the cohort were calculated using the Kaplan-Meier method. Disease characteristics were evaluated for significance using the Fischer's exact test and Wilcoxon rank sum test. Patients were predominantly Caucasian males with a median age of 54 years. A majority, 86% of these patients, had metastatic disease at time of initial presentation, primarily with lung and lymph node involvement. The ORR and CR with HD IL-2 was 10% and 5%, respectively. Initial localized disease presentation is the only variable that was significantly associated with response to HD IL-2 (p = 0.0158). Number of HD IL-2 doses did not correlate with response with a mean of 16.5 and 15.0 total doses in responders and non-responders, respectively (p = 0.53). Median PFS with HD IL-2 was 7.9 months (95% CI, 5.0-21.3). Median OS was 30.5 months (95% CI 13.3-57.66). Within the subset of patients who had progression on IL-2, median OS was 19.4 months (95% CI, 13.3-35.3). In patients who received second-line therapy, median PFS was 7.9 months (95% CI 2.4-10.2). In patients with mRCC with sarcomatoid features, use of HD IL-2 was associated with a modest ORR and a higher survival compared to historical controls (patients with mRCC and sarcomatoid features). Thus, HD IL-2 may have a role in treating selected patients with mRCC with sarcomatoid features.

Differentiation of three biotypes of Malassezia species on human normal skin. correspondence with M. globosa, M. sympodialis and M. restricta.

PubMed

Aspiroz, C; Moreno, L A; Rezusta, A; Rubio, C

1999-01-01

One hundred and twenty lipid dependent Malassezia spp. isolates were obtained from the clinically normal skin of 38 healthy adult volunteers by swabbing three different body sites (back, chest and scalp). Ninety-six percent of these strains could be grouped into three biotypes on the basis of microscopic, cultural, metabolic and biochemical (catalase, esculin and lipase (C-14)) characteristics. The differential features were simple to determine and easily reproduced. Moreover, the three biotypes were referable to the species M. globosa (biotype 1), M. sympodialis (biotype 2) and M. restricta (biotype 3). Based on their microscopic features, cultural properties and body site locations, we suggest that biotype 1 /M. globosa corresponds to the description of Pityrosporum orbiculare (round yeast cells with a narrow base, very frequently found on the upper trunk), and biotype 3/M. restricta corresponds to the concept of P. ovale (oval yeast cells with a broad budding base, located mainly on the scalp). Pleomorphic biotype 2/M. sympodialis, most frequently found in the back, does not clearly fit into any of the Pityrosporum species.

Protective Effects of Trehalose on the Corneal Epithelial Cells

PubMed Central

Aragona, Pasquale; Colosi, Pietro; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Purpose. Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Methods. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. Results. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Conclusions. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls. PMID:25045743

Protective effects of trehalose on the corneal epithelial cells.

PubMed

Aragona, Pasquale; Colosi, Pietro; Rania, Laura; Colosi, Francesca; Pisani, Antonina; Puzzolo, Domenico; Micali, Antonio

2014-01-01

Aim of the present work was to evaluate the effects of the trehalose on the corneal epithelium undergoing alcohol delamination. Twelve patients undergoing laser subepithelial keratomileusis (LASEK) were consecutively included in the study. The right eyes were pretreated with 3% trehalose eye drops, whilst left eyes were used as control. Epithelial specimens were processed for cells vitality assessment, apoptosis, and light and transmission electron microscopy; a morphometric analysis was performed in both groups. In both trehalose-untreated eyes (TUE) and trehalose-treated eyes (TTE), the percentage of vital cells was similar and no apoptotic cells were observed. In TUE, the corneal epithelium showed superficial cells with reduced microfolds, wing cells with vesicles and dilated intercellular spaces, and dark basal cells with vesicles and wide clefts. In TTE, superficial and wing cells were better preserved, and basal cells were generally clear with intracytoplasmatic vesicles. The morphometric analysis showed statistically significant differences between the two groups: the TTE epithelial height was higher, the basal cells showed larger area and clearer cytoplasm. The distribution of desmosomes and hemidesmosomes was significantly different between the groups. Trehalose administration better preserved morphological and morphometric features of alcohol-treated corneal epithelium, when compared to controls.

Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94.

PubMed

Cheent, Kuldeep S; Jamil, Khaleel M; Cassidy, Sorcha; Liu, Mengya; Mbiribindi, Berenice; Mulder, Arend; Claas, Frans H J; Purbhoo, Marco A; Khakoo, Salim I

2013-10-15

Peptide selectivity is a feature of inhibitory receptors for MHC class I expressed by natural killer (NK) cells. CD94-NKG2A operates in tandem with the polymorphic killer cell Ig-like receptors (KIR) and Ly49 systems to inhibit NK cells. However, the benefits of having two distinct inhibitory receptor-ligand systems are not clear. We show that noninhibitory peptides presented by HLA-E can augment the inhibition of NKG2A(+) NK cells mediated by MHC class I signal peptides through the engagement of CD94 without a signaling partner. Thus, CD94 is a peptide-selective NK cell receptor, and NK cells can be regulated by nonsignaling interactions. We also show that KIR(+) and NKG2A(+) NK cells respond with differing stoichiometries to MHC class I down-regulation. MHC-I-bound peptide functions as a molecular rheostat controlling NK cell function. Selected peptides which in isolation do not inhibit NK cells can have different effects on KIR and NKG2A receptors. Thus, these two inhibitory systems may complement each other by having distinct responses to bound peptide and surface levels of MHC class I.

Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94

PubMed Central

Cheent, Kuldeep S.; Jamil, Khaleel M.; Cassidy, Sorcha; Liu, Mengya; Mbiribindi, Berenice; Mulder, Arend; Claas, Frans H. J.; Purbhoo, Marco A.; Khakoo, Salim I.

2013-01-01

Peptide selectivity is a feature of inhibitory receptors for MHC class I expressed by natural killer (NK) cells. CD94–NKG2A operates in tandem with the polymorphic killer cell Ig-like receptors (KIR) and Ly49 systems to inhibit NK cells. However, the benefits of having two distinct inhibitory receptor–ligand systems are not clear. We show that noninhibitory peptides presented by HLA-E can augment the inhibition of NKG2A+ NK cells mediated by MHC class I signal peptides through the engagement of CD94 without a signaling partner. Thus, CD94 is a peptide-selective NK cell receptor, and NK cells can be regulated by nonsignaling interactions. We also show that KIR+ and NKG2A+ NK cells respond with differing stoichiometries to MHC class I down-regulation. MHC-I–bound peptide functions as a molecular rheostat controlling NK cell function. Selected peptides which in isolation do not inhibit NK cells can have different effects on KIR and NKG2A receptors. Thus, these two inhibitory systems may complement each other by having distinct responses to bound peptide and surface levels of MHC class I. PMID:24082146

Direct head-to-head comparison of cationic liposome-mediated gene delivery to mesenchymal stem/stromal cells of different human sources: a comprehensive study.

PubMed

Boura, Joana S; Santos, Francisco Dos; Gimble, Jeffrey M; Cardoso, Carla M P; Madeira, Catarina; Cabral, Joaquim M S; Silva, Cláudia Lobato da

2013-02-01

Nonviral gene delivery to human mesenchymal stem/stromal cells (MSC) can be considered a very promising strategy to improve their intrinsic features, amplifying the therapeutic potential of these cells for clinical applications. In this work, we performed a comprehensive comparison of liposome-mediated gene transfer efficiencies to MSC derived from different human sources-bone marrow (BM MSC), adipose tissue-derived cells (ASC), and umbilical cord matrix (UCM MSC). The results obtained using a green fluorescent protein (GFP)-encoding plasmid indicated that MSC isolated from BM and UCM are more amenable to genetic modification when compared to ASC as they exhibited superior levels of viable, GFP(+) cells 48 hr post-transfection, 58 ± 7.1% and 54 ± 3.8%, respectively, versus 33 ± 4.7%. For all cell sources, high cell recoveries (≈50%) and viabilities (>85%) were achieved, and the transgene expression was maintained for 10 days. Levels of plasmid DNA uptake, as well as kinetics of transgene expression and cellular division, were also determined. Importantly, modified cells were found to retain their characteristic immunophenotypic profile and multilineage differentiation capacity. By using the lipofection protocol optimized herein, we were able to maximize transfection efficiencies to human MSC (maximum of 74% total GFP(+) cells) and show that lipofection is a promising transfection strategy for MSC genetic modification, especially when a transient expression of a therapeutic gene is required. Importantly, we also clearly demonstrated that intrinsic features of MSC from different sources should be taken into consideration when developing and optimizing strategies for MSC engineering with a therapeutic gene.

Quantitative CRISPR interference screens in yeast identify chemical-genetic interactions and new rules for guide RNA design.

PubMed

Smith, Justin D; Suresh, Sundari; Schlecht, Ulrich; Wu, Manhong; Wagih, Omar; Peltz, Gary; Davis, Ronald W; Steinmetz, Lars M; Parts, Leopold; St Onge, Robert P

2016-03-08

Genome-scale CRISPR interference (CRISPRi) has been used in human cell lines; however, the features of effective guide RNAs (gRNAs) in different organisms have not been well characterized. Here, we define rules that determine gRNA effectiveness for transcriptional repression in Saccharomyces cerevisiae. We create an inducible single plasmid CRISPRi system for gene repression in yeast, and use it to analyze fitness effects of gRNAs under 18 small molecule treatments. Our approach correctly identifies previously described chemical-genetic interactions, as well as a new mechanism of suppressing fluconazole toxicity by repression of the ERG25 gene. Assessment of multiple target loci across treatments using gRNA libraries allows us to determine generalizable features associated with gRNA efficacy. Guides that target regions with low nucleosome occupancy and high chromatin accessibility are clearly more effective. We also find that the best region to target gRNAs is between the transcription start site (TSS) and 200 bp upstream of the TSS. Finally, unlike nuclease-proficient Cas9 in human cells, the specificity of truncated gRNAs (18 nt of complementarity to the target) is not clearly superior to full-length gRNAs (20 nt of complementarity), as truncated gRNAs are generally less potent against both mismatched and perfectly matched targets. Our results establish a powerful functional and chemical genomics screening method and provide guidelines for designing effective gRNAs, which consider chromatin state and position relative to the target gene TSS. These findings will enable effective library design and genome-wide programmable gene repression in many genetic backgrounds.

18F-FDG PET radiomics approaches: comparing and clustering features in cervical cancer.

PubMed

Tsujikawa, Tetsuya; Rahman, Tasmiah; Yamamoto, Makoto; Yamada, Shizuka; Tsuyoshi, Hideaki; Kiyono, Yasushi; Kimura, Hirohiko; Yoshida, Yoshio; Okazawa, Hidehiko

2017-11-01

The aims of our study were to find the textural features on 18 F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between 18 F-FDG PET textural features in cervical cancer. Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment 18 F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively. These features were compared between SCC and NSCC using a Bonferroni adjusted P value threshold of 0.0028 (0.05/18). To assess the association between PET features, a heat map analysis with hierarchical clustering, one of the radiomics approaches, was performed. Among 18 PET features, correlation, a second-order textural feature derived from NGLCM, was a stable parameter and it was the only feature which showed a robust trend toward significant difference between SCC and NSCC. Cervical SCC showed a higher correlation (0.70 ± 0.07) than NSCC (0.64 ± 0.07, P = 0.0030). The other PET features did not show any significant differences between SCC and NSCC. A higher correlation in SCC might reflect higher structural integrity and stronger spatial/linear relationship of cancer cells compared with NSCC. A heat map with a PET feature dendrogram clearly showed 5 distinct clusters, where correlation belonged to a cluster including MTV and TLG. However, the association between correlation and MTV/TLG was not strong. Correlation was a relatively independent PET feature in cervical cancer. 18 F-FDG PET textural features might reflect the differences in histological architecture between cervical cancer subtypes. PET radiomics approaches reveal the association between PET features and will be useful for finding a single feature or a combination of features leading to precise diagnoses, potential prognostic models, and effective therapeutic strategies.

Mucosal melanoma: correlation of clinicopathologic, prognostic, and molecular features.

PubMed

Gru, Alejandro A; Becker, Nils; Dehner, Louis P; Pfeifer, John D

2014-08-01

Although the presence of the t(12;22)(q13;q12) translocation (the defining molecular feature of malignant melanoma of soft parts/clear cell sarcoma) in cutaneous melanoma has been investigated, no large-scale studies have been performed among mucosal melanoma (MucM). In this study we assessed the prevalence of the EWSR1 rearrangement in primary MucM, and analyzed gross and microscopic features with their potential impact on diagnosis and prognosis. Overall, 132 specimens from 84 patients were included. A total of 55 cases had an intramucosal component. Survival of MucMs of the head and neck was associated with two independent factors: size and histology. Tumors more than 3 cm in greatest dimension had an average survival of 12.75 months; those 3 cm or less had an average survival of 38.3 months (P=0.035). Purely epithelioid tumors had an average worse survival of 16.8 months (P=0.028). A cut-off value of 1 mm for Breslow depth provided a statistically significant difference in survival at both 3 and 5 years (P=-0.02) by multivariate analysis in the gynecologic tract. At the molecular level three cases had a EWSR1 rearrangement by fluorescent in-situ hybridization, but only one with an intramucosal component. None of the 58 cases tested by PCR showed the presence of the EWSR1 rearrangement. With the exception of vulvar melanomas, the prognosis of mucosal-associated melanomas was poor and there was a suggestion that spindle morphology may be more favorable. Our study also showed that the EWSR1 rearrangement was very uncommon among MucM. Though 'clear cell sarcoma' is embedded in the sarcoma literature, the synonym 'melanoma of soft parts' has considerable justification in light of our evolving understanding of the molecular genetics in the family of malignant melanomas.

Novel Insights into DNA Methylation Features in Spermatozoa: Stability and Peculiarities

PubMed Central

Sayols, Sergi; Chianese, Chiara; Giachini, Claudia; Heyn, Holger; Esteller, Manel

2012-01-01

Data about the entire sperm DNA methylome are limited to two sperm donors whereas studies dealing with a greater number of subjects focused only on a few genes or were based on low resolution arrays. This implies that information about what we can consider as a normal sperm DNA methylome and whether it is stable among different normozoospermic individuals is still missing. The definition of the DNA methylation profile of normozoospermic men, the entity of inter-individual variability and the epigenetic characterization of quality-fractioned sperm subpopulations in the same subject (intra-individual variability) are relevant for a better understanding of pathological conditions. We addressed these questions by using the high resolution Infinium 450K methylation array and compared normal sperm DNA methylomes against somatic and cancer cells. Our study, based on the largest number of subjects (n = 8) ever considered for such a large number of CpGs (n = 487,517), provided clear evidence for i) a highly conserved DNA methylation profile among normozoospermic subjects; ii) a stable sperm DNA methylation pattern in different quality-fractioned sperm populations of the same individual. The latter finding is particularly relevant if we consider that different quality fractioned sperm subpopulations show differences in their structural features, metabolic and genomic profiles. We demonstrate, for the first time, that DNA methylation in normozoospermic men remains highly uniform regardless the quality of sperm subpopulations. In addition, our analysis provided both confirmatory and novel data concerning the sperm DNA methylome, including its peculiar features in respect to somatic and cancer cells. Our description about a highly polarized sperm DNA methylation profile, the clearly distinct genomic and functional organization of hypo- versus hypermethylated loci as well as the association of histone-enriched hypomethylated loci with embryonic development, which we now extended also to hypomethylated piRNAs-linked genes, provides solid basis for future basic and clinical research. PMID:23071498

The role of alginate in Pseudomonas aeruginosa EPS adherence, viscoelastic properties and cell attachment.

PubMed

Orgad, Oded; Oren, Yoram; Walker, Sharon L; Herzberg, Moshe

2011-08-01

Among various functions, extracellular polymeric substances (EPS) provide microbial biofilms with mechanical stability and affect initial cell attachment, the first stage in the biofilm formation process. The role of alginate, an abundant polysaccharide in Pseudomonas aeruginosa biofilms, in the viscoelastic properties and adhesion kinetics of EPS was analyzed using a quartz crystal microbalance with dissipation (QCM-D) monitoring technology. EPS was extracted from two P. aeruginosa biofilms, a wild type strain, PAO1, and a mucoid strain, PAOmucA22 that over-expresses alginate production. The higher alginate content in the EPS originating from the mucoid biofilms was clearly shown to increase both the rate and the extent of attachment of the EPS, as well as the layer's thickness. Also, the presence of calcium and elevated ionic strength increased the thickness of the EPS layer. Dynamic light scattering (DLS) showed that the presence of calcium and elevated ionic strength induced intermolecular attractive interactions in the mucoid EPS molecules. For the wild type EPS, in the presence of calcium, an elevated shift in the distribution of the diffusion coefficients was observed with DLS due to a more compacted conformation of the EPS molecules. Moreover, the alginate over-expression effect on EPS adherence was compared to the effect of alginate over-expression on P. aeruginosa cell attachment. In a parallel plate flow cell, under similar hydraulic and aquatic conditions as those applied for the EPS adsorption tests in the QCM-D flow cell, reduced adherence of the mucoid strain was clearly observed compared to the wild type isogenic bacteria. The results suggest that alginate contributes to steric hindrance and shielding of cell surface features and adhesins that are known to promote cell attachment. © 2011 Taylor & Francis

Downregulation of long non-coding RNA ENSG00000241684 is associated with poor prognosis in advanced clear cell renal cell carcinoma.

PubMed

Su, Hengchuan; Wang, Hongkai; Shi, Guohai; Zhang, Hailiang; Sun, Fukang; Ye, Dingwei

2018-06-01

In order to identify potential novel biomarkers of advanced clear cell renal cell carcinoma (ccRCC), we re-evaluated published long non-coding RNA (lncRNA) expression profiling data. The lncRNA expression profiles in ccRCC microarray dataset GSE47352 were analyzed and an independent cohort of 61 clinical samples including 21 advanced and 40 localized ccRCC patients was used to confirm the most statistically significant lncRNAs by real time PCR. Next, the relationships between the selected lncRNAs and ccRCC patients' clinicopathological features were investigated. The effects of LncRNAs on the invasion and proliferation of renal carcinoma cells were also investigated. The PCR results in a cohort of 21 advanced ccRCC and 40 localized ccRCC tissues were used for confirmation of the selected lncRNAs which were statistically most significant. The PCR results showed that the expression of three LncRNA (ENSG00000241684, ENSG00000231721 and NEAT1) were significantly downregulated in advanced ccRCC. Kaplan-Meier analysis revealed that reduced expression of LncRNA ENSG00000241684 and NEAT1 were significantly associated with poor overall survival. The univariate and multivariate Cox regression indicated LncRNA ENSG00000241684 had significant hazard ratios for predicting clinical outcome. LncRNA ENSG00000241684 expression was negatively correlated with pTNM stage. Overexpression of ENSG00000241684 significantly impaired cell proliferation and reduced the invasion ability in 786-O and ACHN cells. lncRNAs are involved in renal carcinogenesis and decreased lncRNA ENSG00000241684 expression may be an independent adverse prognostic factor in advanced ccRCC patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Merkel cell carcinoma: Do you know your guidelines?

PubMed

Miles, Brett A; Goldenberg, David

2016-05-01

Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy that exhibits clinically aggressive features and is associated with a poor prognosis. The incidence of MCC seems to be increasing for reasons unknown, and is estimated to be 0.32/100,000 in the United States. This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of MCC. Resection of MCC with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy. High-risk patients should undergo adjuvant radiotherapy, which improves oncologic outcomes. The role of chemotherapy is less clear and is currently reserved for advanced-stage MCC and palliative therapy. The pathogenesis of MCC has recently been impacted with the discovery of the Merkel cell polyomavirus (MCPyV). Research to establish targeted and immunologic therapeutic options are ongoing. © 2015 Wiley Periodicals, Inc.

Insights in Anaphylaxis and Clonal Mast Cell Disorders.

PubMed

González-de-Olano, David; Álvarez-Twose, Iván

2017-01-01

The prevalence of anaphylaxis among patients with clonal mast cell disorders (MCD) is clearly higher comparing to the general population. Due to a lower frequency of symptoms outside of acute episodes, clonal MCD in the absence of skin lesions might sometimes be difficult to identify which may lead to underdiagnosis, and anaphylaxis is commonly the presenting symptom in these patients. Although the release of mast cell (MC) mediators upon MC activation might present with a wide variety of symptoms, particular clinical features typically characterize MC mediator release episodes in patients with clonal MCD without skin involvement. Final diagnosis requires a bone marrow study, and it is recommended that this should be done in reference centers. In this article, we address the main triggers for anaphylaxis, risk factors, clinical presentation, diagnosis, and management of patients with MC activation syndromes (MCASs), with special emphasis on clonal MCAS [systemic mastocytosis and mono(clonal) MC activations syndromes].

Insights in Anaphylaxis and Clonal Mast Cell Disorders

PubMed Central

González-de-Olano, David; Álvarez-Twose, Iván

2017-01-01

The prevalence of anaphylaxis among patients with clonal mast cell disorders (MCD) is clearly higher comparing to the general population. Due to a lower frequency of symptoms outside of acute episodes, clonal MCD in the absence of skin lesions might sometimes be difficult to identify which may lead to underdiagnosis, and anaphylaxis is commonly the presenting symptom in these patients. Although the release of mast cell (MC) mediators upon MC activation might present with a wide variety of symptoms, particular clinical features typically characterize MC mediator release episodes in patients with clonal MCD without skin involvement. Final diagnosis requires a bone marrow study, and it is recommended that this should be done in reference centers. In this article, we address the main triggers for anaphylaxis, risk factors, clinical presentation, diagnosis, and management of patients with MC activation syndromes (MCASs), with special emphasis on clonal MCAS [systemic mastocytosis and mono(clonal) MC activations syndromes]. PMID:28740494

[Clear cell acanthoma with dendritica cells charged with melanine and fat].

PubMed

Sánchez Yus, E; Iglesias Díez, L

1975-01-01

A Clear Cell Acanthoma is presented, located in the abdominal region, in a 60-year old man, who had had it all his life. The lesion was warty in appearance and brown in colour. Histologically, among the clear cells, numerous dendrytical cells were found which simultaneously contained melanine grains and small drops of neutral fat. These findings are discussed.

Deep feature classification of angiomyolipoma without visible fat and renal cell carcinoma in abdominal contrast-enhanced CT images with texture image patches and hand-crafted feature concatenation.

PubMed

Lee, Hansang; Hong, Helen; Kim, Junmo; Jung, Dae Chul

2018-04-01

To develop an automatic deep feature classification (DFC) method for distinguishing benign angiomyolipoma without visible fat (AMLwvf) from malignant clear cell renal cell carcinoma (ccRCC) from abdominal contrast-enhanced computer tomography (CE CT) images. A dataset including 80 abdominal CT images of 39 AMLwvf and 41 ccRCC patients was used. We proposed a DFC method for differentiating the small renal masses (SRM) into AMLwvf and ccRCC using the combination of hand-crafted and deep features, and machine learning classifiers. First, 71-dimensional hand-crafted features (HCF) of texture and shape were extracted from the SRM contours. Second, 1000-4000-dimensional deep features (DF) were extracted from the ImageNet pretrained deep learning model with the SRM image patches. In DF extraction, we proposed the texture image patches (TIP) to emphasize the texture information inside the mass in DFs and reduce the mass size variability. Finally, the two features were concatenated and the random forest (RF) classifier was trained on these concatenated features to classify the types of SRMs. The proposed method was tested on our dataset using leave-one-out cross-validation and evaluated using accuracy, sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and area under receiver operating characteristics curve (AUC). In experiments, the combinations of four deep learning models, AlexNet, VGGNet, GoogleNet, and ResNet, and four input image patches, including original, masked, mass-size, and texture image patches, were compared and analyzed. In qualitative evaluation, we observed the change in feature distributions between the proposed and comparative methods using tSNE method. In quantitative evaluation, we evaluated and compared the classification results, and observed that (a) the proposed HCF + DF outperformed HCF-only and DF-only, (b) AlexNet showed generally the best performances among the CNN models, and (c) the proposed TIPs not only achieved the competitive performances among the input patches, but also steady performance regardless of CNN models. As a result, the proposed method achieved the accuracy of 76.6 ± 1.4% for the proposed HCF + DF with AlexNet and TIPs, which improved the accuracy by 6.6%p and 8.3%p compared to HCF-only and DF-only, respectively. The proposed shape features and TIPs improved the HCFs and DFs, respectively, and the feature concatenation further enhanced the quality of features for differentiating AMLwvf from ccRCC in abdominal CE CT images. © 2018 American Association of Physicists in Medicine.

Cells in 3D-reconstitutued eccrine sweat gland cell spheroids differentiate into gross cystic disease fluid protein 15-expressing dark secretory cells and carbonic anhydrase II-expressing clear secretory cells.

PubMed

Li, Haihong; Chen, Liyun; Zhang, Mingjun; Zhang, Bingna

2017-07-01

Secretory coils of eccrine sweat glands are composed of myoepithelial cells, dark secretory cells and clear secretory cells. The two types of cells play important roles in sweat secretion. In our previous study, we demonstrated that the 3D-reconstituted eccrine sweat gland cell spheroids differentiate into secretory coil-like structures. However, whether the secretory coil-like structures further differentiate into dark secretory cells and clear secretory cells were is still unknown. In this study, we detected the differentiation of clear and dark secretory cells in the 3D-reconstituted eccrine sweat gland cell spheroids using the dark secretory cell-specific marker, GCDFP-15, and clear secretory cell-specific marker, CAII by immunofluorescence staining. Results showed that there were both GCDFP-15- and CAII-expressing cells in 12-week-old 3D spheroids, similar to native eccrine sweat glands, indicating that the spheroids possess a cellular structure capable of sweat secretion. We conclude that the 12-week 3D spheroids may have secretory capability. Copyright © 2017 Elsevier GmbH. All rights reserved.

SFPQ/PSF-TFE3 renal cell carcinoma: a clinicopathologic study emphasizing extended morphology and reviewing the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite an identical gene fusion.

PubMed

Wang, Xiao-Tong; Xia, Qiu-Yuan; Ni, Hao; Ye, Sheng-Bing; Li, Rui; Wang, Xuan; Shi, Shan-Shan; Zhou, Xiao-Jun; Rao, Qiu

2017-05-01

Xp11 translocation renal cell carcinoma (RCC) with SFPQ/PSF-TFE3 gene fusion is a rare epithelial tumor. Of note, the appearance of the gene fusion does not necessarily mean that it is renal cell carcinoma. The corresponding mesenchymal neoplasms, including Xp11 neoplasm with melanocytic differentiation, TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa) and melanotic Xp11 translocation renal cancer, can also harbor the identical gene fusion. However, the differences between Xp11 translocation RCC and the corresponding mesenchymal neoplasm have only recently been described. Herein, we examined 5 additional cases of SFPQ-TFE3 RCCs using clinicopathologic, immunohistochemical, and molecular analyses. One tumor had the typical morphologic features of SFPQ-TFE3 RCC, whereas other 3 cases demonstrated the unusual morphologic features associated with pseudorosettes formation or clusters of smaller cells, mimicking TFEB RCC. The remaining one showed branching tubules and papillary structure composed of clear and eosinophilic tumor cells. Immunohistochemically, all 5 cases demonstrated moderate (2+) or strong (3+) positive staining for TFE3, PAX-8 and CD10, whereas no cases demonstrated TFEB, Cathepsin K, CA-IX, CK7, Melan-A, or HMB-45 expression. Genetically, the fusion transcripts were identified in 3 cases by reverse-transcription polymerase chain reaction (RT-PCR). On the basis of fluorescence in situ hybridization (FISH) analysis, all the cases were detected with SFPQ-TFE3 gene fusion. Clinical follow-up data were available for all the patients, and no one developed tumor recurrence, progression, or metastasis. We also review the differences between SFPQ-TFE3 RCC and the corresponding mesenchymal neoplasm despite the identical gene fusion. The presence of pseudorosettes also expands the known histological features of SFPQ-TFE3 RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Establishment and characterization of a novel lymphangiosarcoma cell line (MO-LAS) compared with the hemangiosarcoma cell line (ISO-HAS).

PubMed

Masuzawa, Mikio; Masuzawa, Mamiko; Hamada, Yuhko; Arakawa, Nobuko; Mori, Mari; Ishii, Masako; Nishiyama, Shigeo

2012-08-01

The concept of "lymphangiosarcoma" remains obscure. Therefore, we reported a patient with lymphangiosarcoma, resistant to immunotherapy. The patient presented with impressive and discriminative features: clinically an ill-defined edematous lesion with lymphorrhea and pathologically atypical vascular channel formation without extravasation of blood, clearly distinguished from common angiosarcoma with hemorrhage. From this case, a lymphangiosarcoma cell line, MO-LAS, was established and its characteristics were compared with the hemangiosarcoma cell line, ISO-HAS. Flow cytometric analysis revealed that MO-LAS was negative for factor VIII-related antigen, but positive for CD31, D2-40, NZ-1, and vascular endothelial growth factor receptor-3 (VEGFR-3), similar to ISO-HAS. However, MO-LAS expressed a much higher level of homeobox gene PROX1, indicating a lymphatic phenotype, compared with ISO-HAS. Furthermore, MO-LAS showed a much lesser expression of oncogenes and much lower sensitivity against lymphokine-activated killer (LAK) cells. Lymphangiosarcoma may be difficult to recognize by the immune system. Conclusively, the establishment of MO-LAS, a novel angiosarcoma cell line bearing lymphatic characters, strongly suggests the entity of lymphangiosarcoma.

Programmed cell death progressively models the development of anther sporophytic tissues from the tapetum and is triggered in pollen grains during maturation.

PubMed

Varnier, Anne-Lise; Mazeyrat-Gourbeyre, Florence; Sangwan, Rajbir S; Clément, Christophe

2005-11-01

To characterize the spatial and temporal occurrence of programmed cell death (PCD) in Lilium anther tissues, we used both microscopical and molecular markers of apoptosis for developmental stages from meiosis to pollen release. The first hallmarks of PCD include cell condensation and shrinkage of the cytoplasm, separation of chromatin into delineated masses, and DNA fragmentation in the tapetum as early as the premeiosis stage. PCD then extended to other anther sporophytic tissues, leading to anther dehiscence. Although the PCD clearly affected the endothecium and the epidermis, these two cell layers remained alive until anther dehiscence. In pollen, no sign of PCD was found until pollen mitosis I, after what apoptotic features developed progressively in the vegetative cell. In addition, DNA ladders were detected in all sporophytic tissues and cell types throughout pollen development, whereas in the male gametophyte DNA ladders were only detected during pollen maturation. Our data suggest that PCD is a progressive and active process affecting all the anther tissues, first being triggered in the tapetum.

RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines.

PubMed

Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, Marialucia; Raggi, Chiara; Gissi, Clarissa; D'Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C

2017-10-10

Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell lines: HuH7, Hep3B, HepG2 (hepato-cellular carcinoma) and HuH6 (hepatoblastoma), generating two different sets of sequencing libraries for each. One library was size-selected for small RNAs and the other targeted the whole transcriptome. Here are reported genome wide data of the expression level of coding and non-coding transcripts, microRNAs, isomiRs and snoRNAs providing the first comprehensive overview of the extracellular-vesicle RNA cargo released from LC cell lines. The EV-RNA expression profiles of the four liver cancer cell lines share a similar background, but cell-specific features clearly emerge showing the marked heterogeneity of the EV-cargo among the individual cell lines, evident both for the coding and non-coding RNA species.

Perivascular Epithelioid Cell Tumor of the Uterus with Ovarian Involvement: A Case Report and Review of the Literature

PubMed Central

Fitzpatrick, Megan; Pulver, Tanya; Klein, Molly; Murugan, Paari; Khalifa, Mahmoud; Amin, Khalid

2016-01-01

Patient: Female, 61 Final Diagnosis: Uterine PEComa with ovarian involvement Symptoms: Palpable abdominal mass Medication: — Clinical Procedure: Hysterectomy and bilateral salpingo-oophorectomy Specialty: Obstetrics and Gynecology Objective: Rare disease Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of neoplasms composed of epithelioid cells that express both melanocytic and myoid markers. When considering PEComas of the female genital tract, the uterus is the most common location. Involvement of the ovary in the context of a primary uterine PEComa, in the absence of systemic disease associated with tuberous sclerosis, however, has only been reported in 1 previous case. Case Report: We report a case of a PEComa of the uterus with metastasis to the left ovary in a 61-year-old Caucasian woman. Gross examination of the uterus revealed a 10.7×10.5×10.2 cm tan-brown, mostly solid, partially cystic mass. Microscopic examination showed epithelioid cells with clear to eosinophilic cytoplasm, arranged in fascicles. Intranuclear pseudoinclusions were also noted. The tumor cells were smooth muscle actin, caldesmon, and desmin positive (diffuse); HMB-45 positive (focal); and Melan-A, AE1/AE3, CD10, and S100 negative by immunohistochemistry. Conclusions: Distinguishing among mesenchymal neoplasms, including PEComas, endometrial stromal sarcomas, and leiomyosarcomas, can be difficult. Careful analysis of morphologic and immunohistochemical features is of the utmost importance. Differential diagnosis, including morphologic features and immunohistochemical patterns, is also discussed. PMID:27150246

Condensing Raman spectrum for single-cell phenotype analysis.

PubMed

Sun, Shiwei; Wang, Xuetao; Gao, Xin; Ren, Lihui; Su, Xiaoquan; Bu, Dongbo; Ning, Kang

2015-01-01

In recent years, high throughput and non-invasive Raman spectrometry technique has matured as an effective approach to identification of individual cells by species, even in complex, mixed populations. Raman profiling is an appealing optical microscopic method to achieve this. To fully utilize Raman proling for single-cell analysis, an extensive understanding of Raman spectra is necessary to answer questions such as which filtering methodologies are effective for pre-processing of Raman spectra, what strains can be distinguished by Raman spectra, and what features serve best as Raman-based biomarkers for single-cells, etc. In this work, we have proposed an approach called rDisc to discretize the original Raman spectrum into only a few (usually less than 20) representative peaks (Raman shifts). The approach has advantages in removing noises, and condensing the original spectrum. In particular, effective signal processing procedures were designed to eliminate noise, utilising wavelet transform denoising, baseline correction, and signal normalization. In the discretizing process, representative peaks were selected to signicantly decrease the Raman data size. More importantly, the selected peaks are chosen as suitable to serve as key biological markers to differentiate species and other cellular features. Additionally, the classication performance of discretized spectra was found to be comparable to full spectrum having more than 1000 Raman shifts. Overall, the discretized spectrum needs about 5storage space of a full spectrum and the processing speed is considerably faster. This makes rDisc clearly superior to other methods for single-cell classication.

Differentiation of breast cancer cells in vitro is promoted by the concurrent influence of myoepithelial cells and relaxin.

PubMed Central

Bani, D.; Riva, A.; Bigazzi, M.; Bani Sacchi, T.

1994-01-01

Our previous studies showed that relaxin promotes differentiation of MCF-7 breast adenocarcinoma cells. In the current investigation, we aimed to elucidate whether the effect of the hormone is potentiated when MCF-7 cells are grown together with myoepithelial cells, thus creating a microenvironment reminiscent of the organised tissue architecture of the mammary parenchyma in vivo. The findings obtained reveal that most MCF-7 cells cultured alone have an undifferentiated, blast-like phenotype, only a minority showing a more differentiated phenotype with more organelles and rudimentary intercellular junctions. When co-cultured with myoepithelial cells more MCF-7 cells acquire ultrastructural features consistent with a more differentiated phenotype, such as a rich organellular complement, apical microvilli and intercellular junctions. When relaxin was added to the co-cultures, the ultrastructural signs of differentiation could be observed in even more MCF-7 cells and became more pronounced than in the absence of the hormone, judged by the appearance of a clear-cut polarisation of cytoplasmic organelles, an almost continuous coat of apical microvilli and numerous intracellular pseudolumina. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7947095

Proflavine Hemisulfate as a Fluorescent Contrast Agent for Point-of-Care Cytology

PubMed Central

Prieto, Sandra P.; Powless, Amy J.; Boice, Jackson W.; Sharma, Shree G.; Muldoon, Timothy J.

2015-01-01

Proflavine hemisulfate, an acridine-derived fluorescent dye, can be used as a rapid stain for cytologic examination of biological specimens. Proflavine fluorescently stains cell nuclei and cytoplasmic structures, owing to its small amphipathic structure and ability to intercalate DNA. In this manuscript, we demonstrated the use of proflavine as a rapid cytologic dye on a number of specimens, including normal exfoliated oral squamous cells, cultured human oral squamous carcinoma cells, and leukocytes derived from whole blood specimens using a custom-built, portable, LED-illuminated fluorescence microscope. No incubation time was needed after suspending cells in 0.01% (w/v) proflavine diluted in saline. Images of proflavine stained oral cells had clearly visible nuclei as well as granular cytoplasm, while stained leukocytes exhibited bright nuclei, and highlighted the multilobar nature of nuclei in neutrophils. We also demonstrated the utility of quantitative analysis of digital images of proflavine stained cells, which can be used to detect significant morphological differences between different cell types. Proflavine stained oral cells have well-defined nuclei and cell membranes which allowed for quantitative analysis of nuclear to cytoplasmic ratios, as well as image texture analysis to extract quantitative image features. PMID:25962131

Proflavine Hemisulfate as a Fluorescent Contrast Agent for Point-of-Care Cytology.

PubMed

Prieto, Sandra P; Powless, Amy J; Boice, Jackson W; Sharma, Shree G; Muldoon, Timothy J

2015-01-01

Proflavine hemisulfate, an acridine-derived fluorescent dye, can be used as a rapid stain for cytologic examination of biological specimens. Proflavine fluorescently stains cell nuclei and cytoplasmic structures, owing to its small amphipathic structure and ability to intercalate DNA. In this manuscript, we demonstrated the use of proflavine as a rapid cytologic dye on a number of specimens, including normal exfoliated oral squamous cells, cultured human oral squamous carcinoma cells, and leukocytes derived from whole blood specimens using a custom-built, portable, LED-illuminated fluorescence microscope. No incubation time was needed after suspending cells in 0.01% (w/v) proflavine diluted in saline. Images of proflavine stained oral cells had clearly visible nuclei as well as granular cytoplasm, while stained leukocytes exhibited bright nuclei, and highlighted the multilobar nature of nuclei in neutrophils. We also demonstrated the utility of quantitative analysis of digital images of proflavine stained cells, which can be used to detect significant morphological differences between different cell types. Proflavine stained oral cells have well-defined nuclei and cell membranes which allowed for quantitative analysis of nuclear to cytoplasmic ratios, as well as image texture analysis to extract quantitative image features.

Cell purification: a new challenge for biobanks.

PubMed

Almeida, Maria; García-Montero, Andres C; Orfao, Alberto

2014-01-01

Performing '-omics' analyses on heterogeneous biological tissue samples, such as blood or bone marrow, can lead to biased or even erroneous results, particularly when the targeted cells and/or molecules are present at relatively low percentages/amounts. In such cases, whole sample analysis will most probably dilute and mask the features of the cell and/or molecules of interest, and this will negatively impact the results and their interpretation. Therefore, frequently it is critically important to have well-characterized and high-quality purified cell populations for the reliable detection of subtle variations in their specific features, such as gene expression profile, protein expression pattern and metabolic status. Biobanks are technological platforms which aim to provide researchers access to a large number of high-quality biological samples and their associated data, particularly to support high-quality scientific and clinical research projects, and such projects will benefit enormously by having access to high-quality purified cell populations or their biological components (e.g. DNA, RNA, proteins). Therefore, a clear opportunity exists for preparative cell sorting techniques in biobanks. Although multiple different cell purification approaches exist or are under development (e.g. cell purification techniques based on cell adherence, density and/or cell size properties, methods based on antibody binding as well as new lab-on-a-chip purification techniques), the choice for a specific technology depends on multiple variables, including cell recovery, purity and yield, among others. In addition, most cell purification approaches are not well suited for high-throughput (HT) purification of multiple cell populations coexisting in a sample. Here we review the most (currently) used cell sorting methods that may be applied for sample preparation in biobanks. For the different approaches, technical considerations about their advantages and limitations are highlighted, and the requirements to be met by a HT cell sorting technology to be used in biobanks are also discussed.

Alpha-fetoprotein-producing ovarian clear cell adenocarcinoma with fetal gut differentiation: a rare case report and literature review.

PubMed

Chao, Wei-Ting; Liu, Chia-Hao; Lai, Chiung-Ru; Chen, Yi-Jen; Chuang, Chi-Mu; Wang, Peng-Hui

2018-06-22

Alpha-fetoprotein (AFP) is a useful tumor marker for ovarian germ cell tumors, particularly yolk sac tumor (YST). It is valuable for both diagnosis and further follow-up. Epithelial ovarian carcinoma (EOC) rarely secretes AFP, especially for clear cell type and in the postmenopausal women. Based on the limited knowledge about AFP-producing clear cell type EOC, a case and literature review on this topic is extensively reviewed. We report a 55-year-old postmenopausal woman experienced vaginal spotting for one month, and serum level of AFP was 60,721 ng/ml initially. Histological examination was clear cell type EOC. Tumor cells revealed strong immunoreactivity for glypican-3 (GPC3) and AFP and weak for hepatocyte nuclear factor-1 beta (HNF-1 beta), but negative for CD30, making the diagnosis of AFP-producing clear cell type EOC with fetal gut differentiation in focal areas, FIGO (International Federation of Gynecology and Obstetrics) IIIc. Although the patient underwent an intensive treatment, including optimal debulking surgery and multi-agent chemotherapy, the patient died of disease. To provide a better understanding of clinical and molecular characteristics of the AFP-producing clear cell type EOC, we conducted a systematic literature review. A total of three papers described the AFP-producing clear cell type EOC are available. The overall survival rate of these cases, including the current case is 50%. Although immunohistochemical examination is not always needed in routine for the diagnosis of clear cell type EOC, to distinguish from other tumors, especially germ cell tumors, or to provide the better way to monitor therapeutic response or to evaluate the disease status, immunostaining, including GPC3, HNF-1 beta, CD30, cytokeratin 7 or 20, and AFP is taken into account. Due to rarity, the appropriate chemotherapy regimen and the biological behavior of AFP-producing clear cell type EOC are still unclear.

Malignant perivascular epithelioid cell tumor of the gallbladder: a case report and review of literature.

PubMed

Zhao, Liena; Anders, Karl H

2014-09-01

Perivascular epithelioid cell tumors are rare mesenchymal neoplasms composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. The perivascular epithelioid cell tumor family includes angiomyolipoma, clear cell sugar tumor of the lung, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomic sites. Perivascular epithelioid cell tumors have been reported previously in various sites, but to our knowledge not in the gallbladder. We report here, for the first time, a malignant perivascular epithelioid cell tumor arising in the gallbladder.

Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients.

PubMed

Zamarrón, Alicia; García, Marta; Río, Marcela Del; Larcher, Fernando; Juarranz, Ángeles

2017-09-29

PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role.

Effects of photodynamic therapy on dermal fibroblasts from xeroderma pigmentosum and Gorlin-Goltz syndrome patients

PubMed Central

Zamarrón, Alicia; García, Marta; Río, Marcela Del; Larcher, Fernando; Juarranz, Ángeles

2017-01-01

PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes. Given the demonstrated role of cancer associated fibroblasts (CAFs) in tumor progression and the putative CAFs features of some cancer-prone genodermatoses fibroblasts, in this study, we have further characterized the phenotype of XP and GS dermal fibroblasts and evaluated their response to methyl-δ-aminolevulinic acid (MAL)-PDT compared to that of dermal fibroblasts obtained from healthy donors. We show here that XP/GS fibroblasts display clear features of CAFs and present a significantly higher response to PDT, even after being stimulated with UV light, underscoring the value of this therapeutic approach for these rare skin conditions and likely to other forms of skin cancer were CAFs play a major role. PMID:29100394

Ischemia-induced glomerular parietal epithelial cells hyperplasia: Commonly misdiagnosed cellular crescent in renal biopsy.

PubMed

Zeng, Yeting; Wang, Xinrui; Xie, Feilai; Zheng, Zhiyong

2017-08-01

Ischemic pseudo-cellular crescent (IPCC) that is induced by ischemia and composed of hyperplastic glomerular parietal epithelial cells resembles cellular crescent. In this study, we aimed to assess the clinical and pathological features of IPCC in renal biopsy to avoid over-diagnosis and to determine the diagnostic basis. 4 IPCC cases diagnosed over a 4-year period (2012-2015) were evaluated for the study. Meanwhile, 5 cases of ANCA-associated glomerulonephritis and 5 cases of lupus nephritis (LN) were selected as control. Appropriate clinical data, morphology, and immunohistochemical features of all cases were retrieved. Results showed that the basement membrane of glomerulus with IPCC appeared as a concentric twisted ball, and glomerular cells of the lesion were reduced even entirely absent, and the adjacent afferent arterioles showed sclerosis or luminal stenosis. Furthermore, immune globulin deposition, vasculitis, and fibrinous exudate have not been observed in IPCC. While the cellular crescents showed diverse characteristics in both morphology and immunostaining in the control group. Therefore, these results indicated that IPCC is a sort of ischemic reactive hyperplasia and associated with sclerosis, stenosis, or obstruction of adjacent afferent arterioles, which is clearly different from cellular crescents result from glomerulonephritis. Copyright © 2017 Elsevier GmbH. All rights reserved.

Single Neuron Optimization as a Basis for Accurate Biophysical Modeling: The Case of Cerebellar Granule Cells.

PubMed

Masoli, Stefano; Rizza, Martina F; Sgritta, Martina; Van Geit, Werner; Schürmann, Felix; D'Angelo, Egidio

2017-01-01

In realistic neuronal modeling, once the ionic channel complement has been defined, the maximum ionic conductance (G i-max ) values need to be tuned in order to match the firing pattern revealed by electrophysiological recordings. Recently, selection/mutation genetic algorithms have been proposed to efficiently and automatically tune these parameters. Nonetheless, since similar firing patterns can be achieved through different combinations of G i-max values, it is not clear how well these algorithms approximate the corresponding properties of real cells. Here we have evaluated the issue by exploiting a unique opportunity offered by the cerebellar granule cell (GrC), which is electrotonically compact and has therefore allowed the direct experimental measurement of ionic currents. Previous models were constructed using empirical tuning of G i-max values to match the original data set. Here, by using repetitive discharge patterns as a template, the optimization procedure yielded models that closely approximated the experimental G i-max values. These models, in addition to repetitive firing, captured additional features, including inward rectification, near-threshold oscillations, and resonance, which were not used as features. Thus, parameter optimization using genetic algorithms provided an efficient modeling strategy for reconstructing the biophysical properties of neurons and for the subsequent reconstruction of large-scale neuronal network models.

Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

PubMed

Mizuno, T; Suzuki, N; Makino, H; Furui, T; Morii, E; Aoki, H; Kunisada, T; Yano, M; Kuji, S; Hirashima, Y; Arakawa, A; Nishio, S; Ushijima, K; Ito, K; Itani, Y; Morishige, K

2015-05-01

In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Age-related hearing impairment and the triad of acquired hearing loss

PubMed Central

Yang, Chao-Hui; Schrepfer, Thomas; Schacht, Jochen

2015-01-01

Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise. PMID:26283913

Morphopathological features in tissues of alpha-mannosidosis guinea pigs at different gestational ages.

PubMed

Auclair, D; Hopwood, J J

2007-10-01

Alpha-mannosidosis is an inherited metabolic disorder characterized by a reduction in alpha-D-mannosidase and intralysosomal accumulation of undegraded mannose-containing oligosaccharides. The alpha-mannosidosis guinea pig exhibits pathological similarities to its human counterpart, which make it a valuable animal model. To trace the progression of alpha-mannosidosis during foetal development, brain and visceral organs from affected and unaffected guinea pigs at 30, 36, 38, 51 and 65 days of gestation (dg) were examined by light and electron microscopy (term: approximately 68 dg). In the affected brain, distended lysosomes (vacuoles) were scarce up to 38 dg and were seen in few differentiating neuronal cells but mostly in macrophages, pericytes and endothelial cells. At 51 and 65 dg, several vacuoles were observed in some neurones, in many Purkinje cells, pericytes, endothelial and microglial cells, and in few cerebellar internal granule cells. Myelination had started by 51 dg. Non-myelinated axonal spheroids were detected in the brainstem at 65 dg. In the kidney cortex and liver, an increase in vacuolation was noticed between 36 and 65 dg. Some vacuolated cells were also noticed in the lungs and spleen at 51 and 65 dg. Altogether, these histological observations suggest that alpha-mannosidosis is unlikely to affect ontogenesis before the second half of gestation in guinea pigs; however, the morphopathological features recorded during the last quarter of gestation (which may roughly correspond to the period covering near term to 1-2 years of age in human) were clearly noticeable and may have had some impact.

Initial leukemic gene expression profiles of patients with poor in vivo prednisone response are similar to those of blasts persisting under prednisone treatment in childhood acute lymphoblastic leukemia.

PubMed

Cario, Gunnar; Fetz, Andrea; Bretscher, Christian; Möricke, Anja; Schrauder, Andre; Stanulla, Martin; Schrappe, Martin

2008-09-01

Response to initial glucocorticoid (GC) treatment is a strong prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with a poor prednisone response (PPR) have a poor event-free survival as compared to those with a good prednisone response (PGR). Causes of prednisone resistance are still not well understood. We hypothesized that GC resistance is an intrinsic feature of ALL cells which is reflected in the gene expression pattern and analyzed genome-wide gene expression using microarrays. A case-control study was performed comparing gene expression profiles from initial ALL samples of 20 patients with PPR and those of 20 patients with PGR. Differential gene expression of a subset of genes was confirmed by real-time quantitative polymerase chain reaction analysis and validation was performed in a second independent patient sample (n=20). We identified 121 genes that clearly distinguished prednisone-resistant from sensitive ALL samples (FDR<5%, fold change>or=1.5). Differential gene expression of 21 of these genes could be validated in a second independent set. Of importance, there was a remarkable concordance of genes identified by comparing expression signatures of PPR and PGR cells at diagnosis and those previously described to be up- or downregulated in leukemic cells persisting under GC treatment. Thus, GC resistance seems at least in part to be an intrinsic feature of leukemic cells. Leukemic cells of patients with PPR are characterized by gene expression pattern which are similar to those of resistant cells persisting under glucocorticoid treatment.

Endometrial Serous Carcinoma With Clear-Cell Change: Frequency and Immunohistochemical Analysis.

PubMed

Hariri, Nosaibah; Qarmali, Morad; Fadare, Oluwole

2018-04-01

The diagnostic distinction between endometrial serous carcinoma (ESC) and endometrial clear-cell carcinoma (CCC) may occasionally be problematic, and one potentially contributing factor is the finding of clear cells in otherwise classic cases of ESC. This study aimed to define the frequency of this finding and comparatively assessed the immunophenotype of the clear cells. A review of 56 cases of ESC identified 8 (14.28%) with clear cells, representing 1% to 20% (median 7.5) of tumoral volume in these cases. In only 3 cases were clear cells discernible at low (×20) magnification. There was no significant difference in stage distribution or age between ESC patients with and without clear cells. The immunophenotypes of ESC-associated clear cells (group 1) were compared with foci of conventional ESC on another tissue block within the same case (group 2; n = 8) as well as a randomly selected cohort of CCC cases (group 3; n = 8). Groups 1 and 2 showed no significant differences regarding p53, ER, PR, Napsin-A, p504S, and hepatocyte nuclear factor 1β (HNF1β) expression, or regarding mitotic indices or Ki67 proliferation rate. In contrast, group 1 cases showed an immunophenotypic profile that was notably different from that of group 3 cases, with the former showing statistically significantly higher/more frequent expression of ER, PR, Ki67, and p53 and lower/less frequent expression of Napsin-A, p504S, and HNF1β. We conclude that clear-cell change is seen in 14% of ESCs and is discernible at low magnification in only 5%; these areas show an immunophenotype that is essentially identical to the associated background conventional ESC and are phenotypically dissimilar to CCC.

Histochemical carbonic anhydrase in rat inner medullary collecting duct

NASA Technical Reports Server (NTRS)

Kleinman, J. G.; Bain, J. L.; Fritsche, C.; Riley, D. A.

1992-01-01

Rat inner medullary collecting duct (IMCD) secretes substantial amounts of H+. However, carbonic anhydrase (CA), a concomitant of H+ secretion, has been generally reported absent in this segment. To reexamine this problem, we investigated CA and the morphological phenotypes of cells comprising the IMCD by CA histochemistry, using a modified Hansson technique with light and electron microscopy. Throughout the medulla, tubule cells exhibit histochemical CA activity. In the initial third of the inner medulla, a small proportion have features of intercalated cells and demonstrate some degree of CA activity. However, the majority population in the early portions of the IMCD appears to consist of principal cells. These also show CA staining of widely variable intensity, both among and within cells. A third cell type, previously called "IMCD cells", appears in the middle portion of the IMCD and is the only cell type present near the papilla tip. In contrast to previous reports, these "IMCD cells" have histochemical CA staining, also of highly variable intensity. These results demonstrate that stainable carbonic anhydrase to support acidification is present throughout the rat IMCD, both in intercalated cells and in some cells clearly not of this type. Therefore, the presence of CA is not specific for the intercalated cell type and suggests that other cell types may participate in acid secretion in IMCD.

HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

PubMed

Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

2006-02-01

HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

Intensive probing of a clear air convective field by radar and instrumental drone aircraft.

NASA Technical Reports Server (NTRS)

Rowland, J. R.

1973-01-01

An instrumented drone aircraft was used in conjunction with ultrasensitive radar to study the development of a convective field in the clear air. Radar data are presented which show an initial constant growth rate in the height of the convective field of 3.8 m/min, followed by a short period marked by condensation and rapid growth at a rate in excess of 6.1 m/min. Drone aircraft soundings show general features of a convective field including progressive lifting of the inversion at the top of the convection and a cooling of the air at the top of the field. Calculations of vertical heat flux as a function of time and altitude during the early stages of convection show a linear decrease in heat flux with altitude to near the top of the convective field and a negative heat flux at the top. Evidence is presented which supports previous observations that convective cells overshoot their neutral buoyancy level into a region where they are cool and moist compared to their surroundings. Furthermore, only that portion of the convective cell that has overshot its neutral buoyancy level is generally visible to the radar.

Odontogenic Cysts and Neoplasms.

PubMed

Bilodeau, Elizabeth Ann; Collins, Bobby M

2017-03-01

This article reviews a myriad of common and uncommon odontogenic cysts and tumors. The clinical presentation, gross and microscopic features, differential diagnosis, prognosis, and diagnostic pitfalls are addressed for inflammatory cysts (periapical cyst, mandibular infected buccal cyst/paradental cyst), developmental cysts (dentigerous, lateral periodontal, glandular odontogenic, orthokeratinized odontogenic cyst), benign tumors (keratocystic odontogenic tumor, ameloblastoma, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, ameloblastic fibroma and fibroodontoma, odontoma, squamous odontogenic tumor, calcifying cystic odontogenic tumor, primordial odontogenic tumor, central odontogenic fibroma, and odontogenic myxomas), and malignant tumors (clear cell odontogenic carcinoma, ameloblastic carcinoma, ameloblastic fibrosarcoma). Copyright © 2016 Elsevier Inc. All rights reserved.

High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

PubMed

Mayrand, Dominique; Fradette, Julie

2018-01-01

Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

Validation and utilization of a TFE3 break-apart FISH assay for Xp11.2 translocation renal cell carcinoma and alveolar soft part sarcoma.

PubMed

Pradhan, Dinesh; Roy, Somak; Quiroga-Garza, Gabriela; Cieply, Kathleen; Mahaffey, Alyssa L; Bastacky, Sheldon; Dhir, Rajiv; Parwani, Anil V

2015-09-29

Xp11.2 or TFE3 translocation renal cell carcinomas (RCC) and alveolar soft part sarcoma (ASPS) are characterized by chromosome translocations involving the Xp11.2 breakpoint resulting in transcription factor TFE3 gene fusions. The most common translocations documented in TFE3 RCCs are t(X;1) (p11.2;q21) and t(X;17) (p11.2;q25) which leads to fusion of TFE3 gene on Xp11.2 with PRCC or ASPL respectively. TFE3 immunohistochemistry (IHC) has been inconsistent over time due to background staining problems in part related to fixation issues. Karyotyping to detect TFE3 gene rearrangement requires typically unavailable fresh tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) is generally very challenging due to degradation of RNA in archival material. The study objective was to develop and validate a TFE3 break-apart fluorescence in situ hybridization (FISH) assay to confirm Xp11 translocation RCCs and ASPS. Representative sections of formalin-fixed paraffin-embedded tissue blocks were selected in 40 possible cases. Approximately 60 tumor cells were analyzed in the targeted region. The validation of TFE3 FISH was done with 11 negative and two positive cases. Cut off for a positive result was validated as >7.15 % positive nuclei with any pattern of break-apart signals. FISH evaluation was done blinded of the immunohistochemical or karyotype data. Three out of forty cases were positive for the TFE3 break-apart signals by FISH. The negative cases were reported as clear cell RCC with papillary features (10), clear cell RCC with sarcomatoid areas (2), Papillary RCC with clear cell areas (9), Chromophobe RCC (2), RCC, unclassified type (3) and renal medullary carcinoma (1). 3 of the negative cases were consultation cases for renal tumor with unknown histology. Seven negative cases were soft tissue tumor suspicious for ASPS. Our study validates the utility of TFE3 break-apart FISH on formalin-fixed paraffin-embedded tissue sections for diagnosis and confirmation of Xp11.2 translocation RCCs and ASPS.

The Effect of Anatomical Location of Lymph Node Metastases on Cancer Specific Survival in Patients with Clear Cell Renal Cell Carcinoma

PubMed Central

Nini, Alessandro; Larcher, Alessandro; Cianflone, Francesco; Trevisani, Francesco; Terrone, Carlo; Volpe, Alessandro; Regis, Federica; Briganti, Alberto; Salonia, Andrea; Montorsi, Francesco; Bertini, Roberto; Capitanio, Umberto

2018-01-01

Background Positive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND). Objective To describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM). Design, setting and partecipants The study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions. Outcome measurement and statistical analysis Descriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes. Results and limitations Median number of removed LN was 14 (IQR 9–19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI 95%: 1.3–3.9, p < 0.01) represented an independent predictor of CSM. Conclusions When ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes. Patient summary Lymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary kidney tumour, would aid patient risk stratification and multimodality upfront treatment. PMID:29740587

The up side of decidual natural killer cells: new developments in immunology of pregnancy.

PubMed

Jabrane-Ferrat, Nabila; Siewiera, Johan

2014-04-01

Early phases of human pregnancy are associated with the accumulation of a unique subset of natural killer (NK) cells in the maternal decidua. Decidual NK (dNK) cells that are devoid of cytotoxicity play a pivotal role in successful pregnancy. By secreting large amounts of cytokines/chemokines and angiogenic factors, dNK cells participate in all steps of placentation including trophoblast invasion into the maternal endometrium and vascular remodelling. In this review, we summarize some of dNK cell features and discuss more recent exciting data that challenge the conventional view of these cells. Our new data demonstrate that dNK cells undergo fine tuning or even subvert their classical inhibitory machinery and turn into a real defence force in order to prevent the spread of viruses to fetal tissue. Today it is not clear how these phenotypic and functional adaptations impact cellular cross-talk at the fetal-maternal interface and tissue homeostasis. Ultimately, precise understanding of the molecular mechanisms that govern dNK cell plasticity during congenital human cytomegalovirus infection should lead to the design of more robust strategies to reverse immune escape during viral infection and cancer. © 2013 John Wiley & Sons Ltd.

Imaging and quantitative data acquisition of biological cell walls with Atomic Force Microscopy and Scanning Acoustic Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tittmann, B. R.; Xi, X.

This chapter demonstrates the feasibility of Atomic Force Microscopy (AFM) and High Frequency Scanning Acoustic Microscopy (HF-SAM) as tools to characterize biological tissues. Both the AFM and the SAM have shown to provide imaging (with different resolution) and quantitative elasticity measuring abilities. Plant cell walls with minimal disturbance and under conditions of their native state have been examined with these two kinds of microscopy. After descriptions of both the SAM and AFM, their special features and the typical sample preparation is discussed. The sample preparation is focused here on epidermal peels of onion scales and celery epidermis cells which weremore » sectioned for the AFM to visualize the inner surface (closest to the plasma membrane) of the outer epidermal wall. The nm-wide cellulose microfibrils orientation and multilayer structure were clearly observed. The microfibril orientation and alignment tend to be more organized in older scales compared with younger scales. The onion epidermis cell wall was also used as a test analog to study cell wall elasticity by the AFM nanoindentation and the SAM V(z) feature. The novelty in this work was to demonstrate the capability of these two techniques to analyze isolated, single layered plant cell walls in their natural state. AFM nanoindentation was also used to probe the effects of Ethylenediaminetetraacetic acid (EDTA), and calcium ion treatment to modify pectin networks in cell walls. The results suggest a significant modulus increase in the calcium ion treatment and a slight decrease in EDTA treatment. To complement the AFM measurements, the HF-SAM was used to obtain the V(z) signatures of the onion epidermis. These measurements were focused on documenting the effect of pectinase enzyme treatment. The results indicate a significant change in the V(z) signature curves with time into the enzyme treatment. Thus AFM and HF-SAM open the door to a systematic nondestructive structure and mechanical property study of complex biological cell walls. A unique feature of this approach is that both microscopes allow the biological samples to be examined in their natural fluid (water) environment.« less

Fine structure of the dorsal lingual epithelium of the juvenile hawksbill turtle, Eretmochelys imbricata bissa.

PubMed

Iwasaki, S; Asami, T; Wanichanon, C

1996-04-01

Various species of turtles are adapted to different environments, such as freshwater, seawater, and terrestrial habitats. Comparisons of histological and ultrastructural features of the tongue of the juvenile Hawksbill turtle, Eretmochelys imbricata bissa, with those of freshwater turtles should reveal some aspects of the relationship between the structure of the lingual epithelium and the environment. The light microscope, scanning electron microscope and transmission electron microscope were used. Light microscopy revealed that the mucosal epithelium of the tongue was of the keratinized, stratified squamous type. Under the scanning electron microscope, no lingual papillae were visible on the dorsal surface of the tongue. Micropits and the thickening of cell margins were clearly seen on the surface of cells located on the outermost side. The transmission electron microscope revealed that the cells in the intermediate layer were gradually flattened from the basal side to the surface side, as were their nuclei. In the shallow intermediate layer, the cells were significantly flattened, and their nuclei were condensed or had disappeared. The cytoplasm contained keratohyalin granules, tonofibrils, free ribosomes, mitochondria, and rough endoplasmic reticulum. Numerous free ribosomes were attached to the surface of small keratohyalin granules. The cells of the keratinized layer were significantly flattened, and their nuclei had completely disappeared. Most of cytoplasm was filled with keratin fibers of high electron density. Keratin fibers of the shedding cells, which were located on the outermost side of the keratinized layer, appeared looser, and each fiber, which was somewhat thicker than the tonofibrils and tonofilaments, was clearly distinguishable. The lingual epithelium of the juvenile Hawksbill turtle differs significantly from that of the adult freshwater turtle, in spite of the similarity in gross morphology of the tongues of these species.

Immunohistochemical characterization of prototypical endometrial clear cell carcinoma--diagnostic utility of HNF-1β and oestrogen receptor.

PubMed

Hoang, Lien N; Han, Guangming; McConechy, Melissa; Lau, Sherman; Chow, Christine; Gilks, C Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng-Han

2014-03-01

The great majority of ovarian clear cell carcinomas have a hepatocyte nuclear factor 1 homeobox B (HNF-1β)-positive and oestrogen receptor (ER)-negative immunoprofile. However, the pattern of HNF-1β and ER immunostaining in clear cell carcinomas of the endometrium and the usefulness of this panel in distinguishing clear cell carcinoma from other histological types of endometrial carcinoma have yet to be well defined. We examined the immunostaining patterns of HNF-1β, ER and p53 in 15 morphologically classic pure endometrial clear cell carcinomas, and compared these patterns with 15 endometrioid and 15 serous carcinomas of the endometrium. We observed the presence of diffuse (>70%) moderate to strong nuclear HNF-1β staining and negative ER staining in 14 of 15 clear cell carcinomas, with the remaining case showing both diffuse strong nuclear HNF-1β staining and focal ER staining. In comparison, only one of 15 serous carcinomas and none of 15 endometrioid carcinomas showed a combination of diffuse moderate to strong HNF-1β nuclear staining and negative ER staining. Aberrant p53 immunostaining was observed in five of 15 (33%) clear cell carcinomas. Overall, our findings demonstrate that, similarly to the situation for the ovary, a diagnostic panel of HNF-1β and ER may be considered for separating clear cell carcinoma from endometrioid and serous carcinoma of the endometrium. © 2013 John Wiley & Sons Ltd.

A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

ClinicalTrials.gov

2017-11-10

Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

Association between memory B-cells and clinical and immunological features of primary Sjögren's syndrome and Sicca patients.

PubMed

Barcelos, Filipe; Martins, Catarina; Papoila, Ana; Geraldes, Carlos; Cardigos, Joana; Nunes, Glória; Lopes, Teresa; Alves, Nuno; Vaz-Patto, José; Branco, Jaime; Borrego, Luís-Miguel

2018-06-01

B-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.

“String of pearls pattern”: report of three cases of non clear-cell acanthoma*

PubMed Central

Espinosa, Ana Elena Domínguez; Akay, Bengu Nisa; González-Ramírez, Roger Adrian

2017-01-01

The coiled and dotted vessels in a serpiginous arrangement or “string of pearls” is considered a classical vascular pattern associated with clear cell acanthoma. We present three cases of epidermal tumors different from clear cell acanthoma that have the same “string of pearls” vascular pattern. Even though most authors keep considering the “string of pearls” vascular pattern an almost pathognomonic sign of clear-cell acanthoma, the cases presented here suggest that some other epidermal tumors can also show this pattern. PMID:29267474

The Immunoregulatory Effects of Traditional Chinese Medicine on Psoriasis via its Action on Interleukin: Advances and Considerations.

PubMed

Wu, Minfeng; Deng, Yu; Li, Su; Chen, Yu; Guo, Dongjie; Jin, Xingxiu; Xu, Qi; Li, Bin; Li, Fulun

2018-05-08

Psoriasis is a chronic inflammatory cutaneous disease characterized by clinical manifestations of erythema and white scales. The pathogenesis of psoriasis is not yet clear. Despite a combination of hormonal therapy and physiotherapy used in Western medicine, the condition often relapses after withdrawal of drugs. Traditional Chinese medicine (TCM) has therapeutic features and may be a clinically effective formula by regulating unbalanced immune systems, such as by targeting interleukins. In this paper, we review recent research about how Chinese medicine immunoregulates psoriasis via interleukins, and systematically summarizes the related mechanisms. There are three common pathways leading to psoriasis: (1) Th17 cells secrete IL-17, which is stimulated by IL-23; (2) Th1 cells secrete IL-21, TNF-[Formula: see text] and IFN-[Formula: see text], with the help of Th17 cells; (3) Th22 cells secrete IL-22 under the stimulation of Th17 cells. Clinical and experiment data indicate that TCM could modify psoriasis by antagonizing or regulating interleukin and IL-23/IL-17 axis to inhibit the main pathways.

Multicentric epitheliotropic T-cell lymphoma in an African hedgehog (Atelerix albiventris).

PubMed

Chung, Tae-Ho; Kim, Hyo-Jin; Choi, Ul-Soo

2014-12-01

A 2-year-old female African hedgehog was presented with a 5-month history of pruritus, and diffuse spine and hair loss. A dermatologic examination revealed erythema, excoriation, scales, and crusting affecting the face, flanks, forelimbs, hindlimbs, and dorsal and ventral abdomen. Fine-needle aspiration was performed and skin biopsies were taken from several lesions for cytologic and histologic evaluation. The aspirates yielded smears characterized by a monomorphic population of medium-sized to large lymphocytes with scant to moderate amounts of clear to moderately basophilic cytoplasm and distinct nucleoli along with a low number of cytoplasmic fragments. On histopathologic examination, there were dense dermal lymphoid infiltrates invading the dermis and a monomorphic population of round cells that had infiltrated the overlying epidermis. Epitheliotropic cutaneous lymphoma was diagnosed based on morphologic features. Additional immunochemical analysis using anti-CD3 and anti-CD79a antibodies revealed strong CD3 expression by the tumor cells, which confirmed epitheliotropic cutaneous T-cell lymphoma. This is the first description of a multicentric pattern of epitheliotropic cutaneous T-cell lymphoma in an African hedgehog. © 2014 American Society for Veterinary Clinical Pathology.

Meta-Analysis of the Changes of Peripheral Blood T Cell Subsets in Patients with Brucellosis

PubMed Central

Zheng, Rongjiong; Xie, Songsong; Niyazi, Shaniya; Lu, Xiaobo; Zhou, Yan

2018-01-01

Brucellosis is one of the most prevalent zoonotic diseases in the world, but its pathogenesis is not very clear. At present, it is thought that it may be related to the immunity of T cells. The conclusions of related studies are inconsistent, and its clinical significance is not explicit. We searched published articles in electronic databases up to December 2017 identified as relating to the clinical features of human brucellosis in China. Only eight studies had sufficient quality for data extraction. Meta-analysis showed a significantly decreased proportion of CD4+ T cells in human brucellosis patients compared to healthy subject individuals. The frequency of CD8+ T cells was significantly higher in human brucellosis patients than that in the healthy control group. The pooled analysis presented a significant decrease of the CD4+/CD8+ ratio in human brucellosis patients compared to healthy subjects. There is immunologic dysfunction of T lymphocyte in patients with human brucellosis, the CD4+ and CD8+ T cells might be the important factors affecting the progress of brucellosis. PMID:29888294

Resetting cancer stem cell regulatory nodes upon MYC inhibition.

PubMed

Galardi, Silvia; Savino, Mauro; Scagnoli, Fiorella; Pellegatta, Serena; Pisati, Federica; Zambelli, Federico; Illi, Barbara; Annibali, Daniela; Beji, Sara; Orecchini, Elisa; Alberelli, Maria Adele; Apicella, Clara; Fontanella, Rosaria Anna; Michienzi, Alessandro; Finocchiaro, Gaetano; Farace, Maria Giulia; Pavesi, Giulio; Ciafrè, Silvia Anna; Nasi, Sergio

2016-12-01

MYC deregulation is common in human cancer and has a role in sustaining the aggressive cancer stem cell populations. MYC mediates a broad transcriptional response controlling normal biological programmes, but its activity is not clearly understood. We address MYC function in cancer stem cells through the inducible expression of Omomyc-a MYC-derived polypeptide interfering with MYC activity-taking as model the most lethal brain tumour, glioblastoma. Omomyc bridles the key cancer stemlike cell features and affects the tumour microenvironment, inhibiting angiogenesis. This occurs because Omomyc interferes with proper MYC localization and itself associates with the genome, with a preference for sites occupied by MYC This is accompanied by selective repression of master transcription factors for glioblastoma stemlike cell identity such as OLIG2, POU3F2, SOX2, upregulation of effectors of tumour suppression and differentiation such as ID4, MIAT, PTEN, and modulation of the expression of microRNAs that target molecules implicated in glioblastoma growth and invasion such as EGFR and ZEB1. Data support a novel view of MYC as a network stabilizer that strengthens the regulatory nodes of gene expression networks controlling cell phenotype and highlight Omomyc as model molecule for targeting cancer stem cells. © 2016 The Authors.

Disruption of 3D MCF-12A Breast Cell Cultures by Estrogens – An In Vitro Model for ER-Mediated Changes Indicative of Hormonal Carcinogenesis

PubMed Central

Marchese, Stephanie; Silva, Elisabete

2012-01-01

Introduction Estrogens regulate the proliferation of normal and neoplastic breast epithelium. Although the intracellular mechanisms of estrogens in the breast are largely understood, little is known about how they induce changes in the structure of the mammary epithelium, which are characteristic of breast cancer. In vitro three dimensional (3D) cultures of immortalised breast epithelial cells recapitulate features of the breast epithelium in vivo, including formation of growth arrested acini with hollow lumen and basement membrane. This model can also reproduce features of malignant transformation and breast cancer, such as increased cellular proliferation and filling of the lumen. However, a system where a connection between estrogen receptor (ER) activation and disruption of acini formation can be studied to elucidate the role of estrogens is still missing. Methods/Principal Findings We describe an in vitro 3D model for breast glandular structure development, using breast epithelial MCF-12A cells cultured in a reconstituted basement membrane matrix. These cells are estrogen receptor (ER)α, ERβ and G-protein coupled estrogen receptor 1 (GPER) competent, allowing the investigation of the effects of estrogens on mammary gland formation and disruption. Under normal conditions, MCF-12A cells formed organised acini, with deposition of basement membrane and hollow lumen. However, treatment with 17β-estradiol, and the exogenous estrogens bisphenol A and propylparaben resulted in deformed acini and filling of the acinar lumen. When these chemicals were combined with ER and GPER inhibitors (ICI 182,780 and G-15, respectively), the deformed acini recovered normal features, such as a spheroid shape, proliferative arrest and luminal clearing, suggesting a role for the ER and GPER in the estrogenic disruption of acinar formation. Conclusion This new model offers the opportunity to better understand the role of the ER and GPER in the morphogenesis of breast glandular structure as well as the events implicated in breast cancer initiation and progression. PMID:23056216

Multiple beam interference confocal microscopy: a tool for morphological investigation of living cells and tissues

NASA Astrophysics Data System (ADS)

Joshi, Narahari V.; Medina, Honorio

2000-05-01

Multiple beam interference system is used in conjunction with a conventional scanning confocal microscope to examine the morphology and construction of 3D images of Histolytic Ameba and parasite Candida Albicans. The present combination permits to adjoin advantages of both systems, namely the vertical high contrast and optical sectioning. The interference pattern obtained from a multiple internal reflection of a simple, sandwiched between the glass plate and the cover plate, was focussed on an objective of a scanning confocal microscope. According to optical path differences, morphological details were revealed. The combined features, namely improved resolution in z axis, originated from the interference pattern and the optical sectioning of the confocal scanning system, enhance the resolution and contrast dramatically. These features permitted to obtain unprecedented images of Histolytic Ameba and parasite Candida Albicans. Because of the improved contrast, several details like double wall structure of candida, internal structure of ameba are clearly visible.

Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents

NASA Astrophysics Data System (ADS)

Poulose, Aby Cheruvathoor; Veeranarayanan, Srivani; Mohamed, M. Sheikh; Nagaoka, Yutaka; Romero Aburto, Rebeca; Mitcham, Trevor; Ajayan, Pulickel M.; Bouchard, Richard R.; Sakamoto, Yasushi; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

2015-04-01

A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies. Electronic supplementary information (ESI) available: Methodology and additional experimental results. See DOI: 10.1039/c4nr07139e

Endometrial Carcinomas With Clear Cells: A Study of a Heterogeneous Group of Tumors Including Interobserver Variability, Mutation Analysis, and Immunohistochemistry With HNF-1β.

PubMed

Han, Guangming; Soslow, Robert A; Wethington, Stephanie; Levine, Douglas A; Bogomolniy, Faina; Clement, Philip B; Köbel, Martin; Gilks, Blake; DeLair, Deborah

2015-07-01

Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1β; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1β in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41% of 37 cases that had adequate material for study. At least 1 mutation was identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had poor outcomes: 72% of the patients with follow-up information had died of disease. In summary, this study suggests that the current pool of CC is a heterogeneous group of tumors from the morphologic, immunophenotypic, and molecular point of views and that only a percentage of them represent true CC.

Intracellular ion concentrations and cell volume during cholinergic stimulation of eccrine secretory coil cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takemura, T.; Sato, F.; Saga, K.

Methacholine (MCh)-induced changes in intracellular concentrations of Na, K, and Cl (( Na)i, (K)i, and (Cl)i, respectively) and in cellular dry mass (a measure of cell shrinkage) were examined in isolated monkey eccrine sweat secretory coils by electron probe X-ray microanalysis using the peripheral standard method. To further confirm the occurrence of cell shrinkage during MCh stimulation, the change in cell volume of dissociated clear and dark cells were directly determined under a light microscope equipped with differential interference contrast (DIC) optics. X-ray microanalysis revealed a biphasic increase in cellular dry mass in clear cells during continuous MCh stimulation; anmore » initial increase of dry mass to 158% (of control) followed by a plateau at 140%, which correspond to the decrease in cell volume of 37 and 29%, respectively. The latter agrees with the MCh-induced cell shrinkage of 29% in dissociated clear cells. The MCh-induced increase in dry mass in myoepithelial cells was less than half that of clear cells. During the steady state of MCh stimulation, both (K+)i and (Cl)i of clear cells decreased by about 45%, whereas (Na)i increased in such a way to maintain the sum of (Na) i + (K)i constant. There was a small (12-15 mM) increase in (Na)i and a decrease in (K)i in myoepithelial cells during stimulation with MCh. Dissociated dark cells failed to significantly shrink during MCh stimulation. The decrease in (Cl)i in the face of constant (Na)i + (K)i suggests the accumulation of unknown anion(s) inside the clear cell during MCh stimulation.« less

Designing lymphocyte functional structure for optimal signal detection: voilà, T cells.

PubMed

Noest, A J

2000-11-21

One basic task of immune systems is to detect signals from unknown "intruders" amidst a noisy background of harmless signals. To clarify the functional importance of many observed lymphocyte properties, I ask: What properties would a cell have if one designed it according to the theory of optimal detection, with minimal regard for biological constraints? Sparse and reasonable assumptions about the statistics of available signals prove sufficient for deriving many features of the optimal functional structure, in an incremental and modular design. The use of one common formalism guarantees that all parts of the design collaborate to solve the detection task. Detection performance is computed at several stages of the design. Comparison between design variants reveals e.g. the importance of controlling the signal integration time. This predicts that an appropriate control mechanism should exist. Comparing the design to reality, I find a striking similarity with many features of T cells. For example, the formalism dictates clonal specificity, serial receptor triggering, (grades of) anergy, negative and positive selection, co-stimulation, high-zone tolerance, and clonal production of cytokines. Serious mismatches should be found if T cells were hindered by mechanistic constraints or vestiges of their (co-)evolutionary history, but I have not found clear examples. By contrast, fundamental mismatches abound when comparing the design to immune systems of e.g. invertebrates. The wide-ranging differences seem to hinge on the (in)ability to generate a large diversity of receptors. Copyright 2000 Academic Press.

Impacts on Hubble Space Telescope solar arrays: discrimination between natural and man-made particles.

NASA Astrophysics Data System (ADS)

Kearsley, A. T.; Drolshagen, G.; McDonnell, J. A. M.; Mandeville, J.-C.; Moussi, A.

A Post-Flight Investigation was initiated by the European Space Agency to analyze impact fluxes on solar arrays of the Hubble Space Telescope (HST), exposed to space for 8.25 years at approximately 600 km altitude. The solar cells were deployed during servicing mission SM-1 (December 1993), and retrieved by shuttle orbiter Columbia in March 2002 (SM-3B). A sub-panel of 2 m2 was cut from the --V2 wing and cells were selected for in-depth analysis. Twelve cells (9.6x10-3 m2) were surveyed for flux of all craters of sizes greater than 5 microns Dco; six at the NHM, and six at ONERA. Cumulative flux plots reveal slightly greater abundance of very small craters than in a comparable survey of SM-1 cells. Analytical scanning electron microscopy was used to locate impact features and to analyse residues at the NHM. 103 features of 3 -- 4000 micron conchoidal detachment diameter (Dco) were located on a total of 17 solar cells. 78 features show identifiable residue: 36 are Space Debris impacts and 42 Micrometeoroid impacts. Of the remaining 25: 4 contain residue of ambiguous origin, 1 is a minor manufacturing flaw, 1 is obscured by contamination, and 19 are unresolved, lacking recognizable residue. Space debris impacts on the SM-3B cells are all less than 80 microns Dco, dominated by Al- rich residue, probably of solid rocket motor origin, some may be unburnt fuel. Three craters may be sodium metal droplet impacts. No residues from paint pigment, aluminium or ferrous alloys, or copper- and tin-bearing metal were found. All craters larger than 100 microns are of micrometeoroid origin, or unresolved. Most residues are magnesium-iron silicate or iron sulfide. A few craters show vesicular Mg, S, Fe and Ni residue. A single Fe Ni metal residue was found, as well as enigmatic Mg- and S-bearing residues, all considered of micrometeoroid origin. A few Fe-, O- and C-bearing residues were classified as of ambiguous origin. The quality and quantity of residue is clearly linked to the crater pit morphology, with oval pit features containing more identifiable residue, perhaps due to lower peak shock pressures experienced in these oblique-incidence impacts.

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence.

PubMed

Lee, Jia-Ying Joey; Miller, James Alastair; Basu, Sreetama; Kee, Ting-Zhen Vanessa; Loo, Lit-Hsin

2018-06-01

Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their associated quantitative phenotypic features most predictive of in vivo pulmonotoxicity. This approach is called "High-throughput In vitro Phenotypic Profiling for Toxicity Prediction" (HIPPTox). We found that the resulting assay based on two phenotypic features of a human bronchial epithelial cell line, BEAS-2B, can accurately classify 33 reference chemicals with human pulmonotoxicity information (88.8% balance accuracy, 84.6% sensitivity, and 93.0% specificity). In comparison, the predictivity of a standard cell-viability assay on the same set of chemicals is much lower (77.1% balanced accuracy, 84.6% sensitivity, and 69.5% specificity). We also used the assay to evaluate 17 additional test chemicals with unknown/unclear human pulmonotoxicity, and experimentally confirmed that many of the pulmonotoxic reference and predicted-positive test chemicals induce DNA strand breaks and/or activation of the DNA-damage response (DDR) pathway. Therefore, HIPPTox helps us to uncover these common modes-of-action of pulmonotoxic chemicals. HIPPTox may also be applied to other cell types or models, and accelerate the development of predictive in vitro assays for other cell-type- or organ-specific toxicities.

The topography of primate retina: a study of the human, bushbaby, and new- and old-world monkeys.

PubMed

Stone, J; Johnston, E

1981-02-20

The distribution of ganglion cells has been studied in the retinas of four primates: the prosimian bushbaby, the New-World squirrel monkey, the Old-World crab-eating cynamolgous monkey, and the human. The sizes of ganglion cell somas were also measured at a number of retinal locations and compared with similar measurements in the cat retina to test for the presence in primates of retinal specializations such as the visual streak, and for gradients in retinal structure, such as that between temporal and nasal retina. In all four primates, ganglion cell somas in peripheral retina ranged considerably in diameter (6-16 micrometer in the bushbaby, 8-22 micrometer in the squirrel monkey, 8-23 micrometer in the cynamolgous monkey, 8-26 micrometer in the human). It seems likely that the strong physiological correlates of soma size which have been described among cat retinal ganglion cells and among the relay cells of the macaque lateral geniculate nucleus are generally present in primates. In all four primates, evidence was also obtained of a visual streak specialization; the isodensity lines in ganglion cell density maps were horizontally elongated, and small-bodied ganglion cells were relatively more common in the region of the proposed streak than in other areas of peripheral retina. However, the visual streak seems less well developed than in the cat; among the four primate species examined it was best developed in the bushbaby, at least as assessed by the shape of the isodensity lines. All four primates showed a clear foveal specialization, but this feature seemed least developed in the bushbaby. At the fovea, ganglion cells are smaller in soma size than in peripheral retina; they also seemed more uniform in size, although some distinctly larger cells persist in the human and bushbaby. Soma size measurements also provided evidence of a difference between nasal and temporal areas of peripheral retina comparable to that reported for the cat and other species. Thus the primate retinas examined show features, such as the foveal specialization, which seem unique to them among mammals. They also show features, such as nasal-temporal differences in ganglion cell size, and (though weakly developed) a visual streak, which they have in common with other mammals with widely different phylogenetic histories.

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

PubMed

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (<4 cm) without visible fat (14 fat-poor angiomyolipomas, 92 clear cell renal cell carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Melanoma cells revive an embryonic transcriptional network to dictate phenotypic heterogeneity.

PubMed

Vandamme, Niels; Berx, Geert

2014-01-01

Compared to the overwhelming amount of literature describing how epithelial-to-mesenchymal transition (EMT)-inducing transcription factors orchestrate cellular plasticity in embryogenesis and epithelial cells, the functions of these factors in non-epithelial contexts, such as melanoma, are less clear. Melanoma is an aggressive tumor arising from melanocytes, endowed with unique features of cellular plasticity. The reversible phenotype-switching between differentiated and invasive phenotypes is increasingly appreciated as a mechanism accounting for heterogeneity in melanoma and is driven by oncogenic signaling and environmental cues. This phenotypic switch is coupled with an intriguing and somewhat counterintuitive signaling switch of EMT-inducing transcription factors. In contrast to carcinomas, different EMT-inducing transcription factors have antagonizing effects in melanoma. Balancing between these different EMT transcription factors is likely the key to successful metastatic spread of melanoma.

Ulnar nerve sonography in leprosy neuropathy.

PubMed

Wang, Zhu; Liu, Da-Yue; Lei, Yang-Yang; Yang, Zheng; Wang, Wei

2016-01-01

A 23-year-old woman presented with a half-year history of right forearm sensory and motor dysfunction. Ultrasound imaging revealed definite thickening of the right ulnar nerve trunk and inner epineurium, along with heterogeneous hypoechogenicity and unclear nerve fiber bundle. Color Doppler exhibited a rich blood supply, which was clearly different from the normal ulnar nerve presentation with a scarce blood supply. The patient subsequently underwent needle aspiration of the right ulnar nerve, and histopathological examination confirmed that granulomatous nodules had formed with a large number of infiltrating lymphocytes and a plurality of epithelioid cells in the fibrous connective tissues, with visible atypical foam cells and proliferous vascularization, consistent with leprosy. Our report will familiarize readers with the characteristic sonographic features of the ulnar nerve in leprosy, particularly because of the decreasing incidence of leprosy in recent years.

Texture analysis of common renal masses in multiple MR sequences for prediction of pathology

NASA Astrophysics Data System (ADS)

Hoang, Uyen N.; Malayeri, Ashkan A.; Lay, Nathan S.; Summers, Ronald M.; Yao, Jianhua

2017-03-01

This pilot study performs texture analysis on multiple magnetic resonance (MR) images of common renal masses for differentiation of renal cell carcinoma (RCC). Bounding boxes are drawn around each mass on one axial slice in T1 delayed sequence to use for feature extraction and classification. All sequences (T1 delayed, venous, arterial, pre-contrast phases, T2, and T2 fat saturated sequences) are co-registered and texture features are extracted from each sequence simultaneously. Random forest is used to construct models to classify lesions on 96 normal regions, 87 clear cell RCCs, 8 papillary RCCs, and 21 renal oncocytomas; ground truths are verified through pathology reports. The highest performance is seen in random forest model when data from all sequences are used in conjunction, achieving an overall classification accuracy of 83.7%. When using data from one single sequence, the overall accuracies achieved for T1 delayed, venous, arterial, and pre-contrast phase, T2, and T2 fat saturated were 79.1%, 70.5%, 56.2%, 61.0%, 60.0%, and 44.8%, respectively. This demonstrates promising results of utilizing intensity information from multiple MR sequences for accurate classification of renal masses.

High mobility group A1 protein modulates autophagy in cancer cells.

PubMed

Conte, Andrea; Paladino, Simona; Bianco, Gaia; Fasano, Dominga; Gerlini, Raffaele; Tornincasa, Mara; Renna, Maurizio; Fusco, Alfredo; Tramontano, Donatella; Pierantoni, Giovanna Maria

2017-11-01

High Mobility Group A1 (HMGA1) is an architectural chromatin protein whose overexpression is a feature of malignant neoplasias with a causal role in cancer initiation and progression. HMGA1 promotes tumor growth by several mechanisms, including increase of cell proliferation and survival, impairment of DNA repair and induction of chromosome instability. Autophagy is a self-degradative process that, by providing energy sources and removing damaged organelles and misfolded proteins, allows cell survival under stress conditions. On the other hand, hyper-activated autophagy can lead to non-apoptotic programmed cell death. Autophagy deregulation is a common feature of cancer cells in which has a complex role, showing either an oncogenic or tumor suppressor activity, depending on cellular context and tumor stage. Here, we report that depletion of HMGA1 perturbs autophagy by different mechanisms. HMGA1-knockdown increases autophagosome formation by constraining the activity of the mTOR pathway, a major regulator of autophagy, and transcriptionally upregulating the autophagy-initiating kinase Unc-51-like kinase 1 (ULK1). Consistently, functional experiments demonstrate that HMGA1 binds ULK1 promoter region and negatively regulates its transcription. On the other hand, the increase in autophagosomes is not associated to a proportionate increase in their maturation. Overall, the effects of HMGA1 depletion on autophagy are associated to a decrease in cell proliferation and ultimately impact on cancer cells viability. Importantly, silencing of ULK1 prevents the effects of HMGA1-knockdown on cellular proliferation, viability and autophagic activity, highlighting how these effects are, at least in part, mediated by ULK1. Interestingly, this phenomenon is not restricted to skin cancer cells, as similar results have been observed also in HeLa cells silenced for HMGA1. Taken together, these results clearly indicate HMGA1 as a key regulator of the autophagic pathway in cancer cells, thus suggesting a novel mechanism through which HMGA1 can contribute to cancer progression.

Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells

PubMed Central

Rakhmanov, Mirzokhid; Keller, Baerbel; Gutenberger, Sylvia; Foerster, Christian; Hoenig, Manfred; Driessen, Gertjan; van der Burg, Mirjam; van Dongen, Jacques J.; Wiech, Elisabeth; Visentini, Marcella; Quinti, Isabella; Prasse, Antje; Voelxen, Nadine; Salzer, Ulrich; Goldacker, Sigune; Fisch, Paul; Eibel, Hermann; Schwarz, Klaus; Peter, Hans-Hartmut; Warnatz, Klaus

2009-01-01

The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. CD21low B cells are polyclonal, unmutated IgM+IgD+ B cells but carry a highly distinct gene expression profile which differs from conventional naïve B cells. Interestingly, while clearly not representing a memory population, they do share several features with the recently defined memory-like tissue, Fc receptor-like 4 positive B cell population in the tonsils of healthy donors. CD21low B cells show signs of previous activation and proliferation in vivo, while exhibiting defective calcium signaling and poor proliferation in response to B cell receptor stimulation. CD21low B cells express decreased amounts of homeostatic but increased levels of inflammatory chemokine receptors. This might explain their preferential homing to peripheral tissues like the bronchoalveolar space of CVID or the synovium of rheumatoid arthritis patients. Therefore, as a result of the close resemblance to the gene expression profile, phenotype, function and preferential tissue homing of murine B1 B cells, we suggest that CD21low B cells represent a human innate-like B cell population. PMID:19666505

Automated image based prominent nucleoli detection

PubMed Central

Yap, Choon K.; Kalaw, Emarene M.; Singh, Malay; Chong, Kian T.; Giron, Danilo M.; Huang, Chao-Hui; Cheng, Li; Law, Yan N.; Lee, Hwee Kuan

2015-01-01

Introduction: Nucleolar changes in cancer cells are one of the cytologic features important to the tumor pathologist in cancer assessments of tissue biopsies. However, inter-observer variability and the manual approach to this work hamper the accuracy of the assessment by pathologists. In this paper, we propose a computational method for prominent nucleoli pattern detection. Materials and Methods: Thirty-five hematoxylin and eosin stained images were acquired from prostate cancer, breast cancer, renal clear cell cancer and renal papillary cell cancer tissues. Prostate cancer images were used for the development of a computer-based automated prominent nucleoli pattern detector built on a cascade farm. An ensemble of approximately 1000 cascades was constructed by permuting different combinations of classifiers such as support vector machines, eXclusive component analysis, boosting, and logistic regression. The output of cascades was then combined using the RankBoost algorithm. The output of our prominent nucleoli pattern detector is a ranked set of detected image patches of patterns of prominent nucleoli. Results: The mean number of detected prominent nucleoli patterns in the top 100 ranked detected objects was 58 in the prostate cancer dataset, 68 in the breast cancer dataset, 86 in the renal clear cell cancer dataset, and 76 in the renal papillary cell cancer dataset. The proposed cascade farm performs twice as good as the use of a single cascade proposed in the seminal paper by Viola and Jones. For comparison, a naive algorithm that randomly chooses a pixel as a nucleoli pattern would detect five correct patterns in the first 100 ranked objects. Conclusions: Detection of sparse nucleoli patterns in a large background of highly variable tissue patterns is a difficult challenge our method has overcome. This study developed an accurate prominent nucleoli pattern detector with the potential to be used in the clinical settings. PMID:26167383

Automated image based prominent nucleoli detection.

PubMed

Yap, Choon K; Kalaw, Emarene M; Singh, Malay; Chong, Kian T; Giron, Danilo M; Huang, Chao-Hui; Cheng, Li; Law, Yan N; Lee, Hwee Kuan

2015-01-01

Nucleolar changes in cancer cells are one of the cytologic features important to the tumor pathologist in cancer assessments of tissue biopsies. However, inter-observer variability and the manual approach to this work hamper the accuracy of the assessment by pathologists. In this paper, we propose a computational method for prominent nucleoli pattern detection. Thirty-five hematoxylin and eosin stained images were acquired from prostate cancer, breast cancer, renal clear cell cancer and renal papillary cell cancer tissues. Prostate cancer images were used for the development of a computer-based automated prominent nucleoli pattern detector built on a cascade farm. An ensemble of approximately 1000 cascades was constructed by permuting different combinations of classifiers such as support vector machines, eXclusive component analysis, boosting, and logistic regression. The output of cascades was then combined using the RankBoost algorithm. The output of our prominent nucleoli pattern detector is a ranked set of detected image patches of patterns of prominent nucleoli. The mean number of detected prominent nucleoli patterns in the top 100 ranked detected objects was 58 in the prostate cancer dataset, 68 in the breast cancer dataset, 86 in the renal clear cell cancer dataset, and 76 in the renal papillary cell cancer dataset. The proposed cascade farm performs twice as good as the use of a single cascade proposed in the seminal paper by Viola and Jones. For comparison, a naive algorithm that randomly chooses a pixel as a nucleoli pattern would detect five correct patterns in the first 100 ranked objects. Detection of sparse nucleoli patterns in a large background of highly variable tissue patterns is a difficult challenge our method has overcome. This study developed an accurate prominent nucleoli pattern detector with the potential to be used in the clinical settings.

Decellularized Diaphragmatic Muscle Drives a Constructive Angiogenic Response In Vivo.

PubMed

Alvarèz Fallas, Mario Enrique; Piccoli, Martina; Franzin, Chiara; Sgrò, Alberto; Dedja, Arben; Urbani, Luca; Bertin, Enrica; Trevisan, Caterina; Gamba, Piergiorgio; Burns, Alan J; De Coppi, Paolo; Pozzobon, Michela

2018-04-28

Skeletal muscle tissue engineering (TE) aims to efficiently repair large congenital and acquired defects. Biological acellular scaffolds are considered a good tool for TE, as decellularization allows structural preservation of tissue extracellular matrix (ECM) and conservation of its unique cytokine reservoir and the ability to support angiogenesis, cell viability, and proliferation. This represents a major advantage compared to synthetic scaffolds, which can acquire these features only after modification and show limited biocompatibility. In this work, we describe the ability of a skeletal muscle acellular scaffold to promote vascularization both ex vivo and in vivo. Specifically, chicken chorioallantoic membrane assay and protein array confirmed the presence of pro-angiogenic molecules in the decellularized tissue such as HGF, VEGF, and SDF-1α. The acellular muscle was implanted in BL6/J mice both subcutaneously and ortotopically. In the first condition, the ECM-derived scaffold appeared vascularized 7 days post-implantation. When the decellularized diaphragm was ortotopically applied, newly formed blood vessels containing CD31⁺, αSMA⁺, and vWF⁺ cells were visible inside the scaffold. Systemic injection of Evans Blue proved function and perfusion of the new vessels, underlying a tissue-regenerative activation. On the contrary, the implantation of a synthetic matrix made of polytetrafluoroethylene used as control was only surrounded by vWF⁺ cells, with no cell migration inside the scaffold and clear foreign body reaction (giant cells were visible). The molecular profile and the analysis of macrophages confirmed the tendency of the synthetic scaffold to enhance inflammation instead of regeneration. In conclusion, we identified the angiogenic potential of a skeletal muscle-derived acellular scaffold and the pro-regenerative environment activated in vivo, showing clear evidence that the decellularized diaphragm is a suitable candidate for skeletal muscle tissue engineering and regeneration.

Electron microscopy study of antioxidant interaction with bacterial cells

NASA Astrophysics Data System (ADS)

Plotnikov, Oleg P.; Novikova, Olga V.; Konnov, Nikolai P.; Korsukov, Vladimir N.; Gunkin, Ivan F.; Volkov, Uryi P.

2000-10-01

To maintain native microorganisms genotype and phenotype features a lyophylization technique is widely used. However in this case cells are affected by influences of vacuum and low temperature that cause a part of the cells population to be destruction. Another factor reduced microorganisms vitality is formation of reactive oxygen forms that damage certain biological targets (such as DNA, membranes etc.) Recently to raise microorganism's resistance against adverse condition natural and synthetic antioxidants are used. Antioxidant- are antagonists of free radicals. Introduction of antioxidants in protective medium for lyophylization increase bacteria storage life about 2,0-4,8 fold in comparison with reference samples. In the article the main results of our investigation of antioxidants interaction with microorganism cells is described. As bacteria cells we use vaccine strain yersinia pestis EV, that were grown for 48 h at 28 degree(s)C on the Hottinger agar (pH 7,2). Antioxidants are inserted on the agar surface in specimen under test. To investigate a localization of antioxidants for electron microscopy investigation, thallium organic antioxidants were used. The thallium organic compounds have an antioxidant features if thallium is in low concentration (about 1(mu) g/ml). The localization of the thallium organic antioxidants on bacteria Y. pestis EV is visible in electron microscopy images, thallium being heavy metal with high electron density. The negatively stained bacteria and bacteria thin sections with thallium organic compounds were investigated by means of transmission electron microscopy. The localization of the thallium organic compounds is clearly visible in electron micrographs as small dark spots with size about 10-80nm. Probably mechanisms of interaction of antioxidants with bacteria cells are discussed.

Fine-needle aspiration of a Xp11.2 translocation/TFE3 fusion renal cell carcinoma metastatic to the lung: report of a case and review of the literature.

PubMed

Schinstine, Malcolm; Filie, Armando C; Torres-Cabala, Carlos; Abati, Andrea; Linehan, W Marston; Merino, Maria

2006-11-01

A 57-yr-old woman presented to the National Cancer Institute (NCI) with a history of nephrectomy for a clear cell renal cell carcinoma (RCC), Fuhrman grade 3 of 4 diagnosed 1 yr prior to admission to the NCI. A CT scan done upon admission revealed multiple bilateral lung masses. A CT-guided fine-needle aspiration (FNA) of one of the lung masses revealed a cellular specimen composed primarily of follicular structures surrounding dense hyalinized central cores. The cells in the follicular structures displayed bland nuclei and had granular to vacuolated cytoplasm. Papillary structures were also appreciated. Immunocytochemical studies showed tumor cells that were strongly vimentin and TFE3 positive. Focal staining for AE1/AE3 and CD10 was observed, as was negative staining for EMA. A surgical biopsy specimen reflected the FNA findings and demonstrated a similar immunoprofile. These findings correspond to the recently described Xp11.2 translocation/TFE3 fusion renal cell carcinoma. To our knowledge, this is the first report describing the cytologic features of an Xp11.2 translocation/TFE3 fusion RCC. (C) 2006 Wiley-Liss, Inc.

RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines

PubMed Central

Berardocco, Martina; Radeghieri, Annalisa; Busatto, Sara; Gallorini, Marialucia; Raggi, Chiara; Gissi, Clarissa; D’Agnano, Igea; Bergese, Paolo; Felsani, Armando; Berardi, Anna C.

2017-01-01

Liver cancer (LC) is one of the most common cancers and represents the third highest cause of cancer-related deaths worldwide. Extracellular vesicle (EVs) cargoes, which are selectively enriched in RNA, offer great promise for the diagnosis, prognosis and treatment of LC. Our study analyzed the RNA cargoes of EVs derived from 4 liver-cancer cell lines: HuH7, Hep3B, HepG2 (hepato-cellular carcinoma) and HuH6 (hepatoblastoma), generating two different sets of sequencing libraries for each. One library was size-selected for small RNAs and the other targeted the whole transcriptome. Here are reported genome wide data of the expression level of coding and non-coding transcripts, microRNAs, isomiRs and snoRNAs providing the first comprehensive overview of the extracellular-vesicle RNA cargo released from LC cell lines. The EV-RNA expression profiles of the four liver cancer cell lines share a similar background, but cell-specific features clearly emerge showing the marked heterogeneity of the EV-cargo among the individual cell lines, evident both for the coding and non-coding RNA species. PMID:29137313

Devescovinid trichomonad with axostyle-based rotary motor ("Rubberneckia"): taxonomic assignment as Caduceia versatilis sp. nov

NASA Technical Reports Server (NTRS)

d'Ambrosio, U.; Dolan, M.; Wier, A. M.; Margulis, L.

1999-01-01

An amitochondriate trichomonad cell of the family Devescovinidae (Class Parabasalia), helped demonstrate the fluid model of lipoprotein cell membranes. This wood-ingesting symbiont in the hindgut of the dry wood-eating termite Cryptotermes cavifrons is informally known to cell biologists as "Rubberneckia". As the microtubular axo-style complex generates force causing clockwise movement of the entire anterior portion of the cell at the shear zone the protist displays "head" rotation. Studies by phase contrast and videomicroscopy of live cells, of whole mounts by scanning, and thin sections by transmission electron microscopy extend the observations of Tamm and Tamm [24-26] and Tamm [19-23]. Habitat, cell shape, size, nuclear features, parabasal apparatus and other morphological details permit the assignment of "Rubberneckia" to Kirby's cosmopolitan genus Caduceia. This large-sized devescovinid has distinctive parabasal gyres, an axostylar rotary, motor, and regularly-associated nonflagellated, fusiform and flagellated rod epibiotic surface bacteria. In addition to regularly aligned epibionts intranuclear and endocytoplasmic bacteria are abundant and hydrogenosomes are Present. "Rubberneckia" is compared here to the other seven species of Caduceia. Since it is clearly sufficiently distinctive to warrant new species status, we named it C. versatilis.

Characterizing polymorphic inversions in human genomes by single-cell sequencing

PubMed Central

Sanders, Ashley D.; Hills, Mark; Porubský, David; Guryev, Victor; Falconer, Ester; Lansdorp, Peter M.

2016-01-01

Identifying genomic features that differ between individuals and cells can help uncover the functional variants that drive phenotypes and disease susceptibilities. For this, single-cell studies are paramount, as it becomes increasingly clear that the contribution of rare but functional cellular subpopulations is important for disease prognosis, management, and progression. Until now, studying these associations has been challenged by our inability to map structural rearrangements accurately and comprehensively. To overcome this, we coupled single-cell sequencing of DNA template strands (Strand-seq) with custom analysis software to rapidly discover, map, and genotype genomic rearrangements at high resolution. This allowed us to explore the distribution and frequency of inversions in a heterogeneous cell population, identify several polymorphic domains in complex regions of the genome, and locate rare alleles in the reference assembly. We then mapped the entire genomic complement of inversions within two unrelated individuals to characterize their distinct inversion profiles and built a nonredundant global reference of structural rearrangements in the human genome. The work described here provides a powerful new framework to study structural variation and genomic heterogeneity in single-cell samples, whether from individuals for population studies or tissue types for biomarker discovery. PMID:27472961

Amyloid-linked cellular toxicity triggered by bacterial inclusion bodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez-Montalban, Nuria; Departament de Genetica i de Microbiologia, Universitat Autonoma de Barcelona, Bellaterra, 08193 Barcelona; Ciber de Bioingenieria, Biomateriales y Nanomedicina

The aggregation of proteins in the form of amyloid fibrils and plaques is the characteristic feature of some pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. The mechanisms by which the aggregation processes result in cell damage are under intense investigation but recent data indicate that prefibrillar aggregates are the most proximate mediators of toxicity rather than mature fibrils. Since it has been shown that prefibrillar forms of the nondisease-related misfolded proteins are highly toxic to cultured mammalian cells we have studied the cytoxicity associated to bacterial inclusion bodies that have been recently described as protein deposits presenting amyloid-likemore » structures. We have proved that bacterial inclusion bodies composed by a misfolding-prone {beta}-galactosidase fusion protein are clearly toxic for mammalian cells but the {beta}-galactosidase wild type enzyme forming more structured thermal aggregates does not impair cell viability, despite it also binds and enter into the cells. These results are in the line that the most cytotoxic aggregates are early prefibrilar assemblies but discard the hypothesis that the membrane destabilization is Key event to subsequent disruption of cellular processes, such as ion balance, oxidative state and the eventually cell death.« less

Clear cell adenocarcinoma of the ovary associated with in utero diethylstilbestrol exposure: case report and clinical overview.

PubMed

Dasanu, Constantin A; Herzog, Thomas J

2009-01-01

Clear cell adenocarcinoma of the vagina and cervix were previously shown to be tumors occurring in female offspring exposed prenatally to diethylstilbestrol. This report describes the first clinical case of clear cell adenocarcinoma of the ovary linked to early diethylstilbestrol exposure in utero. A 45-year-old woman presented with a self-discovered lump in the lower abdominal quadrant. She underwent surgery and staging that revealed clear cell adenocarcinoma confined to the left ovary. Foci of high-grade squamous neoplastic proliferation, inflammation, and a paratubal cyst were also present on the pathology specimen. Medical records established unequivocally that the patient's mother received diethylstilbestrol therapy throughout the pregnancy. Our case is consistent with clear cell adenocarcinoma, probably related to diethylstilbestrol exposure in utero. It reinforces the need for continued vigilance in individuals prenatally exposed to this drug.

The Effectiveness of Clear Speech as a Masker

ERIC Educational Resources Information Center

Calandruccio, Lauren; Van Engen, Kristin; Dhar, Sumitrajit; Bradlow, Ann R.

2010-01-01

Purpose: It is established that speaking clearly is an effective means of enhancing intelligibility. Because any signal-processing scheme modeled after known acoustic-phonetic features of clear speech will likely affect both target and competing speech, it is important to understand how speech recognition is affected when a competing speech signal…

CO2 laser debridement of sulphur mustard (bis-2-chloroethyl sulphide) induced cutaneous lesions accelerates production of a normal epidermis with elimination of cytological atypia.

PubMed

Smith, K J; Skelton, H G; Martin, J L; Hurst, C G; Hackley, B E

1997-10-01

Sulphur mustard (bis-2-chloroethyl sulphide; HD) exposure acutely produces lesions that vary from mild erythema, to blister formation, to necrosis. When blisters occur, with or without necrosis, healing of the lesions is delayed. Weanling pigs exposed to a mild erythema-producing dose of HD and to a moderate erythema-producing dose that consistently gave microblister formation were treated with CO2 laser (Tru-Pulse) debridement at 6, 24 or 48 h after exposure. The histopathological features observed at 14 days after exposure in control skin and skin exposed to both HD doses were compared with the features observed in CO2 laser-debrided skin in non-exposed and HD-exposed skin sites. The overlying epidermis in the non-laser treated lesions was thin, with cytological atypia and squamoid changes within the basal cell layer, as well as scattered apoptotic/necrotic keratinocytes. An increased inflammatory infiltrate and necrobiotic changes in the dermis were seen at the higher HD dose. All laser-treated lesions appeared identical, with a thick, differentiated epidermis and a well-formed basal cell layer. There was minimal inflammatory infiltrate. In the papillary dermis there were increased stromal cells. Laser debridement of mild clinical lesions induced by HD produced a more functional epidermis by 14 days as well as clearing the epidermis of damaged keratinocytes.

Chromatin structure of the LCR in the human β-globin locus transcribing the adult δ- and β-globin genes.

PubMed

Kim, Seoyeon; Kim, Yea Woon; Shim, Sung Han; Kim, Chul Geun; Kim, Aeri

2012-03-01

The β-like globin genes are transcribed in a developmental stage specific fashion in erythroid cells. The specific transcription of globin genes is conferred by the locus control region (LCR), but the chromatin structure of the LCR in the human adult β-globin locus transcribing the δ- and β-globin genes is not clear. Here, we employed hybrid MEL cells that contain a human chromosome 11. The δ- and β-globin genes were highly transcribed in hybrid MEL/ch11 cells after transcriptional induction. LCR HS3 and HS2 were strongly occupied by erythroid specific transcriptional activators and co-factors in the induced locus. These HSs, but not HS4 and HS1, were in close proximity with the active globin genes as revealed by high resolution 3C experiments. The active features at HS3 were markedly established after transcriptional induction, while HS2 was in a relatively active conformation before the induction. Unexpectedly, HS1 did not show notable active features except histone hyperacetylation. Taken together, the LCR of the human β-globin locus transcribing the adult δ- and β-globin genes has HS specific chromatin structure. The structure at each HS, which is different from the locus transcribing the fetal globin genes, might relate to its role in transcribing the adult genes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural basis of viral invasion: lessons from paramyxovirus F

PubMed Central

Lamb, Robert A.; Jardetzky, Theodore S.

2007-01-01

Summary The structures of glycoproteins that mediate enveloped virus entry into cells have revealed dramatic structural changes that accompany membrane fusion and provided mechanistic insights into this process. The group of class I viral fusion proteins includes the influenza hemagglutinin, paramyxovirus F, HIV env and other mechanistically related fusogens, but these proteins are unrelated in sequence and exhibit clearly distinct structural features. Recently determined crystal structures of the paramyxovirus F protein in two conformations, representing prefusion and postfusion states, reveal a novel protein architecture that undergoes large-scale, irreversible refolding during membrane fusion, extending our understanding of this diverse group of membrane fusion machines. PMID:17870467

Development of a diffraction imaging flow cytometer

PubMed Central

Jacobs, Kenneth M.; Lu, Jun Q.

2013-01-01

Diffraction images record angle-resolved distribution of scattered light from a particle excited by coherent light and can correlate highly with the 3D morphology of a particle. We present a jet-in-fluid design of flow chamber for acquisition of clear diffraction images in a laminar flow. Diffraction images of polystyrene spheres of different diameters were acquired and found to correlate highly with the calculated ones based on the Mie theory. Fast Fourier transform analysis indicated that the measured images can be used to extract sphere diameter values. These results demonstrate the significant potentials of high-throughput diffraction imaging flow cytometry for extracting 3D morphological features of cells. PMID:19794790

Hyalinizing clear cell carcinoma of the nasopharynx operated by trans-oral and trans-palatal approach.

PubMed

Nakashima, T; Yasumatsu, R; Yamauchi, M; Toh, S; Nakano, T; Yamamoto, H; Komune, S

2015-03-01

Hyalinizing clear cell carcinoma is a rare minor salivary gland neoplasm. The treatment of choice is surgical resection with or without post-operative radiotherapy. This tumour often demonstrates a good prognosis. We report a case of hyalinizing clear cell carcinoma arising in the nasopharynx. A 27-year-old female presented with progressive hearing disturbance and tinnitus. On examination, an expansile mass was observed in her nasopharynx. Biopsy was performed and the pathology results returned as clear cell carcinoma. Surgical resection was performed trans-orally accompanied by trans-palatal approach. She has no recurrence during more than two years of follow up.

Acute myeloblastic leukemia with minimal myeloid differentiation (FAB AML-M0): a study of eleven cases.

PubMed

Sempere, A; Jarque, I; Guinot, M; Palau, J; García, R; Sanz, G F; Gomis, F; Pérez-Sirvent, M L; Senent, L; Sanz, M A

1993-12-01

The main clinical, morphological, cytochemical, immunological features and therapy results of eleven patients diagnosed as acute myeloblastic leukemia M0 (AML-M0) are reported here. There were no clinical characteristics, abnormalities on physical examination or initial laboratory parameters that distinguished these eleven patients. Bone marrow aspirates were hypocellular in four patients. The leukemic cells were undifferentiated by light microscopy and myeloperoxidase (MPO) and/or Sudan Black B (SBB) stains were negative in all cases. Myeloid differentiation antigens were present on the leukemic cells of all eleven patients, whereas B and T cell markers were clearly negative except for CD4 and CD7 antigens. Whatever the treatment employed survival was very short. Eight of the eleven patients were treated and two achieved complete remission (CR) but only one of them is alive in continuous CR. Our results like those previously reported, suggest that AML-M0 patients have a very poor prognosis with standard induction therapies and should perhaps be considered for experimental therapeutic approaches.

Epstein-Barr Virus in Gastric Carcinoma

PubMed Central

Nishikawa, Jun; Yoshiyama, Hironori; Iizasa, Hisashi; Kanehiro, Yuichi; Nakamura, Munetaka; Nishimura, Junichi; Saito, Mari; Okamoto, Takeshi; Sakai, Kouhei; Suehiro, Yutaka; Yamasaki, Takahiro; Oga, Atsunori; Yanai, Hideo; Sakaida, Isao

2014-01-01

The Epstein-Barr virus (EBV) is detected in about 10% of gastric carcinoma cases throughout the world. In EBV-associated gastric carcinoma, all tumor cells harbor the clonal EBV genome. Gastric carcinoma associated with EBV has distinct clinicopathological features, occurs predominately in men and in younger-aged individuals, and presents a generally diffuse histological type. Most cases of EBV-associated gastric carcinoma exhibit a histology rich in lymphocyte infiltration. The immunological reactiveness in the host may represent a relatively preferable prognosis in EBV-positive cases. This fact highlights the important role of EBV in the development of EBV-associated gastric carcinoma. We have clearly proved direct infection of human gastric epithelialcells by EBV. The infection was achieved by using a recombinant EBV. Promotion of growth by EBV infection was observed in the cells. Considerable data suggest that EBV may directly contribute to the development of EBV-associated GC. This tumor-promoting effect seems to involve multiple mechanisms, because EBV affects several host proteins and pathways that normally promote apoptosis and regulate cell proliferation. PMID:25386788

Ultrananocrystalline diamond-coated nanoporous membranes support SK-N-SH neuroblastoma endothelial cell attachment.

PubMed

Yang, Kai-Hung; Nguyen, Alexander K; Goering, Peter L; Sumant, Anirudha V; Narayan, Roger J

2018-06-06

Ultrananocrystalline diamond (UNCD) has been demonstrated to have attractive features for biomedical applications and can be combined with nanoporous membranes for applications in drug delivery systems, biosensing, immunoisolation and single molecule analysis. In this study, free-standing nanoporous UNCD membranes with pore sizes of 100 or 400 nm were fabricated by directly depositing ultrathin UNCD films on nanoporous silicon nitride membranes and then etching away silicon nitride using reactive ion etching. Successful deposition of UNCD on the substrate with a novel process was confirmed with Raman spectroscopy, X-ray photoelectron spectroscopy, cross-section scanning electron microscopy (SEM) and transmission electron microscopy. Both sample types exhibited uniform geometry and maintained a clear hexagonal pore arrangement. Cellular attachment of SK-N-SH neuroblastoma endothelial cells was examined using confocal microscopy and SEM. Attachment of SK-N-SH cells onto UNCD membranes on both porous regions and solid surfaces was shown, indicating the potential use of UNCD membranes in biomedical applications such as biosensors and tissue engineering scaffolds.

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma.

PubMed

Ricketts, Christopher J; De Cubas, Aguirre A; Fan, Huihui; Smith, Christof C; Lang, Martin; Reznik, Ed; Bowlby, Reanne; Gibb, Ewan A; Akbani, Rehan; Beroukhim, Rameen; Bottaro, Donald P; Choueiri, Toni K; Gibbs, Richard A; Godwin, Andrew K; Haake, Scott; Hakimi, A Ari; Henske, Elizabeth P; Hsieh, James J; Ho, Thai H; Kanchi, Rupa S; Krishnan, Bhavani; Kwiatkowski, David J; Lui, Wembin; Merino, Maria J; Mills, Gordon B; Myers, Jerome; Nickerson, Michael L; Reuter, Victor E; Schmidt, Laura S; Shelley, C Simon; Shen, Hui; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Vincent, Benjamin G; Vocke, Cathy D; Wheeler, David A; Yang, Lixing; Kim, William Y; Robertson, A Gordon; Spellman, Paul T; Rathmell, W Kimryn; Linehan, W Marston

2018-04-03

Renal cell carcinoma (RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival. Published by Elsevier Inc.

Atomic Scale Understanding of Poly-Si/SiO2/c-Si Passivated Contacts: Passivation Degradation Due to Metallization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguiar, Jeffery A.; Young, David; Lee, Benjamin

2016-11-21

The key attributes for achieving high efficiency crystalline silicon solar cells include class leading developments in the ability to approach the theoretical limits of silicon solar technology (29.4% efficiency). The push for high efficiency devices is further compounded with the clear need for passivation to reduce recombination at the metal contacts. At the same time there is stringent requirement to retain the same material device quality, surface passivation, and performance characteristics following subsequent processing. The development of passivated silicon cell structures that retain active front and rear surface passivation and overall material cell quality is therefore a relevant and activemore » area of development. To address the potential outcomes of metallization on passivated silicon stack, we report on some common microstructural features of degradation due to metallization for a series of silicon device stacks. A fundamental materials understanding of the metallization process on retaining high-efficiency passivated Si devices is therefore gained over these series of results.« less

The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

PubMed Central

Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young

2015-01-01

Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value for determining the value of VEGF-TKI treatment in patients with mCCRCC. Implications for Practice: Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are essential for the treatment of metastatic renal cell carcinoma patients, but the treatment suffers from a lack of predictive markers. This study demonstrates that PD-L1 expression is a predictor for unfavorable response to VEGF-TKI and a prognostic indicator for poor overall survival and progression-free survival in patients with metastatic clear cell renal cell carcinoma receiving VEGF-TKI. PMID:26424759

Lack of effective systemic therapy for recurrent clear cell carcinoma of the ovary.

PubMed

Crotzer, David R; Sun, Charlotte C; Coleman, Robert L; Wolf, Judith K; Levenback, Charles F; Gershenson, David M

2007-05-01

Clear cell carcinoma of the ovary is an aggressive tumor characterized by relative chemoresistance and a poor prognosis. The purpose of this study was to review our experience with recurrent clear cell carcinoma of the ovary to evaluate its responsiveness to systemic cytotoxic and hormonal agents. All patients diagnosed with clear cell carcinoma of the ovary seen at our institution between 1990 and 2002 were identified and their medical records reviewed. Eligibility criteria were: 1) primary diagnosis of clear cell carcinoma of the ovary, 2) measurable recurrent disease, 3) treatment of recurrent disease with 1 or more systemic regimens, and 4) adequate clinical information. End points were clinical response, progression-free survival, and overall survival. Fifty-one patients treated for recurrent clear cell carcinoma were identified. The patients received a total of 105 regimens (344 cycles of therapy). Among patients with platinum-sensitive disease (n=22 regimens), 2 patients (9%) had partial responses to retreatment with carboplatin plus paclitaxel, and 4 (18%) had stable disease. Among patients with platinum-resistant disease (n=83 regimens), only 1 patient (1%) had a partial response - to gemcitabine - and 1 patient had stable disease in response to 2 different regimens-paclitaxel and gemcitabine. The median progression-free survival was 8 months, and the median overall survival was 18 months. Our findings suggest that recurrent clear cell carcinoma of the ovary is particularly chemoresistant. A continued search for more active, targeted agents is warranted.

Malignant perivascular epithelioid cell tumor (PEComa) of cervix with TFE3 gene rearrangement: a case report.

PubMed

Liu, Feifei; Zhang, Renya; Wang, Zi-Yu; Xia, Qiuyuan; Shen, Qin; Shi, Shanshan; Tu, Pin; Shi, Qunli; Zhou, Xiaojun; Rao, Qiu

2014-01-01

In this study, we reported the first PEComa arising within the cervix with TFE3 gene rearrangement and aggressive biological behavior. Morphologically, the tumor showed infiltrative growth into the surrounding parenchyma. The majority of tumor cells were arrayed in sheets, alveolar structures, or nests separated by delicate fibrovascular septa. There was marked intratumoral hemorrhage, necrosis, and stromal calcifications. The tumor cells had abundant clear cytoplasm, focally containing finely granular dark brown pigment, morphologically considered to be melanin. Immunohistochemically, the tumor cells demonstrated moderately (2+) or strongly (3+) positive staining for TFE3, HMB45, and Melan A but negative for CKpan, SMA, S100, PAX8, and PAX2. The presence of Ki-67 protein demonstrated a moderate proliferation rate, with a few Ki-67-positive nuclei. Using a recently developed TFE3 split FISH assay, the presence of TFE3 rearrangement was demonstrated. All these clinicopathologic features are suggestive of TFE3-rearranged PEComas of the cervix. Our results both expand the known characteristics of primary cervix PEComas and add to the data regarding TFE3 rearrangement-associated PEComas.

Herpes simplex virus in postradiation cervical smears. A morphologic and immunocytochemical study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longatto Filho, A.; Maeda, M.Y.; Oyafuso, M.S.

1990-09-01

From January 1987 to August 1988, cytomorphologic criteria of both herpes simplex virus (HSV) and radiation effects were observed in Papanicolaou smears from 3 of 1,340 patients who had received radiotherapy for squamous cell carcinoma of the cervix. Avidin-biotin immunoperoxidase staining, using a rabbit IgG polyclonal HSV antibody, confirmed the presence of HSV antigen in those three postradiation smears. Both multinucleated molded cells and epithelial cells that lacked cytopathic effects were positive for HSV. Three other postradiation smears from these cases were similarly positive for HSV antigen; the one preradiation smear was negative. In situ hybridization and immunoperoxidase studies onmore » sections from the preradiation biopsies were negative: severely altered neoplastic cells showed no reactivity. The absence of HSV markers in the preradiation specimens suggests that the HSV infections were secondary to the radiotherapy; further studies are needed to prove this association and to assess the possible mechanisms. These cases clearly indicate that the overlapping features of radiation and viral effects (such as multinucleation) may be present simultaneously.« less

Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis

PubMed Central

Navascues, Joaquin; Berciano, Maria T.; Tucker, Karen E.

2006-01-01

Neurite outgrowth is a central feature of neuronal differentiation. PC12 cells are a good model system for studying the peripheral nervous system and the outgrowth of neurites. In addition to the dramatic changes observed in the cytoplasm, neuronal differentiation is also accompanied by striking changes in nuclear morphology. The large and sustained increase in nuclear transcription during neuronal differentiation requires synthesis of a large number of factors involved in pre-mRNA processing. We show that the number and composition of the nuclear subdomains called Cajal bodies and gems changes during the course of N-ras-induced neuritogenesis in the PC12-derived cell line UR61. The Cajal bodies found in undifferentiated cells are largely devoid of the survival of motor neurons (SMN) protein product. As cells shift to a differentiated state, SMN is not only globally upregulated, but is progressively recruited to Cajal bodies. Additional SMN foci (also known as Gemini bodies, gems) can also be detected. Using dual-immunogold labeling electron microscopy and mouse embryonic fibroblasts lacking the coilin protein, we show that gems clearly represent a distinct category of nuclear body. PMID:15164213

T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease.

PubMed

Takeuchi, Mai; Sato, Yasuharu; Ohno, Kyotaro; Tanaka, Satoshi; Takata, Katsuyoshi; Gion, Yuka; Orita, Yorihisa; Ito, Toshihiro; Tachibana, Tomoyasu; Yoshino, Tadashi

2014-08-01

IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGFβ1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading.

PubMed

Streck, Letícia; Sarmento, Víctor H V; Machado, Paula R L; Farias, Kleber J S; Fernandes-Pedrosa, Matheus F; da Silva-Júnior, Arnóbio Antônio

2016-06-30

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment.

Additive manufacturing of lab-on-a-chip devices: promises and challenges

NASA Astrophysics Data System (ADS)

Zhu, Feng; Macdonald, Niall P.; Cooper, Jonathan M.; Wlodkowic, Donald

2013-12-01

This work describes a preliminary investigation of commercially available 3D printing technologies for rapid prototyping and low volume fabrication of Lab-on-a-Chip devices. The main motivation of the work was to use off-the-shelf 3D printing methods in order to rapidly and inexpensively build microfluidic devices with complex geometric features and reduce the need to use clear room environment and conventional microfabrication techniques. Both multi-jet modelling (MJM) and stereolithography (SLA) processes were explored. MJM printed devices were fabricated using a HD3500+ (3D Systems) high-definition printer using a thermo-polymer VisiJet Crystal (3D Systems) substratum that allows for a z-axis resolution of 16 μm and 25 μm x-y accuracy. SLA printed devices were produced using a Viper Pro (3D Systems) stereolithography system using Watershed 11122XC (DSM Somos) and Dreve Fototec 7150 Clear (Dreve Otoplastik GmbH) resins which allow for a z-axis resolution of 50 μm and 25 μm x-y accuracy. Fabrication results compared favourably with other forms of rapid prototyping such as laser cut PMMA devices and PDMS moulded microfluidic devices of the same design. Both processes allowed for fabrication of monolithic, optically transparent devices with features in the 100 μm range requiring minimal post-processing. Optical polymer qualities following different post-processing methods were also tested in both brightfield and fluorescence imaging of transgenic zebrafish embryos. Finally, we show that only ethanol-treated Dreve Fototec 7150 Clear resign proved to be non-toxic to human cell lines and fish embryos in fish toxicity assays (FET) requiring further investigation of 3D printing materials.

Phase Transitions of Isotropic to Anisotropic Biocompatible Lipid-Based Drug Delivery Systems Overcoming Insoluble Benznidazole Loading

PubMed Central

Streck, Letícia; Sarmento, Víctor H. V.; Machado, Paula R. L.; Farias, Kleber J. S.; Fernandes-Pedrosa, Matheus F.; da Silva-Júnior, Arnóbio Antônio

2016-01-01

Previous studies reported low benznidazole (BNZ) loading in conventional emulsions due to the weak interaction of the drug with the most common oils used to produce foods or pharmaceuticals. In this study, we focused on how the type of surfactant, surfactant-to-oil ratio w/w (SOR) and oil-to-water ratio w/w (OWR) change the phase behavior of different lipid-based drug delivery systems (LBDDS) produced by emulsion phase inversion. The surfactant mixture composed of soy phosphatidylcholine and sodium oleate (1:7, w/w, hydrophilic lipophilic balance = 16) stabilized medium chain triglyceride in water. Ten formulations with the clear aspect or less turbid dispersions (five with the SOR ranging from 0.5 to 2.5 and five with the OWR from 0.06 to 0.4) were selected from the phase behavior diagram to assess structural features and drug-loading capacity. The rise in the SOR induced the formation of distinct lipid-based drug delivery systems (nanoemulsions and liquid crystal lamellar type) that were identified using rheological measurements and cross-polarized light microscopy images. Clear dispersions of small and narrow droplet-sized liquid-like nanoemulsions, Newtonian flow-type, were produced at SOR from 0.5 to 1.5 and OWR from 0.12 to 0.4, while clear liquid or gel-like liquid crystals were produced at SOR from 1.5 to 2.5. The BNZ loading was improved according to the composition and type of LBDDS produced, suggesting possible drug location among surfactant layers. The cell viability assays proved the biocompatibility for all of the prepared nanoemulsions at SOR less than 1.5 and liquid crystals at SOR less than 2.5, demonstrating their promising features for the oral or parenteral colloidal delivery systems containing benznidazole for Chagas disease treatment. PMID:27376278

Circulating aldosterone induces the apical accumulation of the proton pumping V-ATPase and increases proton secretion in clear cells in the caput epididymis.

PubMed

Roy, Jeremy W; Hill, Eric; Ruan, Ye Chun; Vedovelli, Luca; Păunescu, Teodor G; Brown, Dennis; Breton, Sylvie

2013-08-15

Clear cells express the vacuolar proton-pumping H(+)-ATPase (V-ATPase) and acidify the lumen of the epididymis, a process that is essential for male fertility. The renin-angiotensin-aldosterone system (RAAS) regulates fluid and electrolyte balance in the epididymis, and a previous study showed binding of aldosterone exclusively to epididymal clear cells (Hinton BT, Keefer DA. Steroid Biochem 23: 231-233, 1985). We examined here the role of aldosterone in the regulation of V-ATPase in the epididymis. RT-PCR showed expression of the mineralocorticoid receptor [MR; nuclear receptor subfamily 3, group C member 2 (NR3C2)] and 11-β-dehydrogenase isozyme 2 (HSD11β2) mRNAs specifically in clear cells, isolated by fluorescence-activated cell sorting from B1-enhanced green fluorescent protein (EGFP) mice. Tail vein injection of adult rats with aldosterone, 1,2-dioctanoyl-sn-glycerol (DOG), or 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) induced V-ATPase apical membrane accumulation and extension of V-ATPase-labeled microvilli in clear cells in the caput epididymis but not in the cauda. V-ATPase activity was measured in EGFP-expressing clear cells using the intracellular pH (pHi)-sensing dye seminaphthorhodafluor-5F-5-(and 6)-carboxylic acid, acetoxymethyl ester acetate (SNARF-5F). Aldosterone induced a rapid increase in the rate of Na(+)- and bicarbonate-independent pHi recovery following an NH4Cl-induced acid load in clear cells isolated from the caput but not the cauda. This effect was abolished by concanamycin A, spironolactone, and chelerythrine but not myristoylated-protein kinase inhibitor (mPKI) or mifepristone. Thus aldosterone increases V-ATPase-dependent proton secretion in clear cells in the caput epididymis via MR/NR3C2 and PKC activation. This study, therefore, identifies aldosterone as an active member of the RAAS for the regulation of luminal acidification in the proximal epididymis.

Malignant odontogenic tumors. A retrospective and collaborative study of seven cases.

PubMed

Mosqueda Taylor, Adalberto; Meneses García, Abelardo; Ruíz Godoy Rivera, Luz María; Suárez Roa, María de Lourdes; Luna Ortiz, Kuauhyama

2003-01-01

The frequency, clinico-pathologic features and outcome of malignant odontogenic tumors diagnosed according to the current WHO classification in three pathology services in Mexico City are presented. There were seven cases (5 male and 2 female patients), which represent less than 4% of all odontogenic tumors diagnosed in these services. There were six odontogenic carcinomas (two malignant ameloblastomas, two clear cell odontogenic carcinomas, one primary intraosseous carcinoma and one carcinoma arising in an odontogenic cyst) and one ameloblastic fibrosarcoma. Age ranged from 25 to 72 years (mean: 43.8). Clear cell odontogenic carcinomas occurred in the canine-premolar region, one in the maxilla and one in the mandible (one ia a man and one in a woman), while the remaining lesions affected the posterior region of the mandible, with a male predominance (4:1), which agrees with previously reported cases. Surgical resection was the treatment employed in all carcinomas, while the ameloblastic fibrosarcoma was treated with chemotherapy due to its large extension, but without favorable response. The patient with primary intraosseous carcinoma had submaxillary and cervical metastases and the neoplasm was the cause of death. In spite of their extremely low frequency, malignant odontogenic tumors are an important cause of extensive surgical procedures in the oral and maxillofacial region.

Protein carriers of conjugate vaccines

PubMed Central

Pichichero, Michael E

2013-01-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

Targeted mutation analysis of endometrial clear cell carcinoma.

PubMed

Hoang, Lien N; McConechy, Melissa K; Meng, Bo; McIntyre, John B; Ewanowich, Carol; Gilks, Cyril Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng-Han

2015-04-01

Endometrial clear cell carcinomas (CCC) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC. We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC. The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A+, hepatocyte nuclear factor-1β (HNF1β(+) ) and oestrogen receptor(-) ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP53 and PPP2R1A mutations, without PTEN, CTNNB1 or ARID1A mutation). No mutations in PTEN, CTNNB1 or POLE were identified. The overall mutation profile of this cohort of endometrial CCC appears to be more serous-like than endometrioid-like, with a minor subset in the TP53-mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC, and underscore the need for further investigations into the oncogenesis of endometrial CCC. © 2014 John Wiley & Sons Ltd.

Reaction and Aggregation Dynamics of Cell Surface Receptors

NASA Astrophysics Data System (ADS)

Wang, Michelle Dong

This dissertation is composed of both theoretical and experimental studies of cell surface receptor reaction and aggregation. Project I studies the reaction rate enhancement due to surface diffusion of a bulk dissolved ligand with its membrane embedded target, using numerical calculations. The results show that the reaction rate enhancement is determined by ligand surface adsorption and desorption kinetic rates, surface and bulk diffusion coefficients, and geometry. In particular, we demonstrate that the ligand surface adsorption and desorption kinetic rates, rather than their ratio (the equilibrium constant), are important in rate enhancement. The second and third projects are studies of acetylcholine receptor clusters on cultured rat myotubes using fluorescence techniques after labeling the receptors with tetramethylrhodamine -alpha-bungarotoxin. The second project studies when and where the clusters form by making time-lapse movies. The movies are made from overlay of the pseudocolored total internal reflection fluorescence (TIRF) images of the cluster, and the schlieren images of the cell cultures. These movies are the first movies made using TIRF, and they clearly show the cluster formation from the myoblast fusion, the first appearance of clusters, and the eventual disappearance of clusters. The third project studies the fine structural features of individual clusters observed under TIRF. The features were characterized with six parameters by developing a novel fluorescence technique: spatial fluorescence autocorrelation. These parameters were then used to study the feature variations with age, and with treatments of drugs (oligomycin and carbachol). The results show little variation with age. However, drug treatment induced significant changes in some parameters. These changes were different for oligomycin and carbachol, which indicates that the two drugs may eliminate clusters through different mechanisms.

Comparative Studies of the Proteome, Glycoproteome, and N-Glycome of Clear Cell Renal Cell Carcinoma Plasma before and after Curative Nephrectomy

PubMed Central

2015-01-01

Clear cell renal cell carcinoma is the most prevalent of all reported kidney cancer cases, and currently there are no markers for early diagnosis. This has stimulated great research interest recently because early detection of the disease can significantly improve the low survival rate. Combining the proteome, glycoproteome, and N-glycome data from clear cell renal cell carcinoma plasma has the potential of identifying candidate markers for early diagnosis and prognosis and/or to monitor disease recurrence. Here, we report on the utilization of a multi-dimensional fractionation approach (12P-M-LAC) and LC–MS/MS to comprehensively investigate clear cell renal cell carcinoma plasma collected before (disease) and after (non-disease) curative nephrectomy (n = 40). Proteins detected in the subproteomes were investigated via label-free quantification. Protein abundance analysis revealed a number of low-level proteins with significant differential expression levels in disease samples, including HSPG2, CD146, ECM1, SELL, SYNE1, and VCAM1. Importantly, we observed a strong correlation between differentially expressed proteins and clinical status of the patient. Investigation of the glycoproteome returned 13 candidate glycoproteins with significant differential M-LAC column binding. Qualitative analysis indicated that 62% of selected candidate glycoproteins showed higher levels (upregulation) in M-LAC bound fraction of disease samples. This observation was further confirmed by released N-glycans data in which 53% of identified N-glycans were present at different levels in plasma in the disease vs non-disease samples. This striking result demonstrates the potential for significant protein glycosylation alterations in clear cell renal cell carcinoma cancer plasma. With future validation in a larger cohort, information derived from this study may lead to the development of clear cell renal cell carcinoma candidate biomarkers. PMID:25184692

Manifestation of anharmonic resonance in the interaction of intense ultrashort laser pulses with microstructured targets

NASA Astrophysics Data System (ADS)

Dalui, Malay; Kundu, M.; Madhu Trivikram, T.; Ray, Krishanu; Krishnamurthy, M.

2016-10-01

Identification of the basic processes responsible for an efficient heating of intense laser produced plasmas is one of the important features of high intensity laser matter interaction studies. Collisionless absorption due to the anharmonicity in the self-consistent electrostatic potential of the plasma, known as anharmonic resonance (AHR), has been proposed to be a basic mechanism but a clear experimental demonstration is needed. Here, we show that microstructured targets enhance X-ray emission and the polarization dependence ascribes the enhancement to anharmonic resonance heating. It is found that p-polarized pulses of 5 ×1017 W/cm2 intensity bring in a 16-fold enhancement in the X-ray emission in the energy range 20-350 keV compared to s-polarized pulses with microstructured targets. This ratio is 2 for the case of polished targets under otherwise identical conditions. Particle-in-cell simulations clearly show that AHR is the key absorption mechanism responsible for this effect.

Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors

ClinicalTrials.gov

2017-06-22

Childhood Renal Cell Carcinoma; Clear Cell Renal Cell Carcinoma; Clear Cell Sarcoma of the Kidney; Papillary Renal Cell Carcinoma; Rhabdoid Tumor of the Kidney; Stage I Renal Cell Cancer; Stage I Renal Wilms Tumor; Stage II Renal Cell Cancer; Stage II Renal Wilms Tumor; Stage III Renal Cell Cancer; Stage III Renal Wilms Tumor; Stage IV Renal Cell Cancer; Stage IV Renal Wilms Tumor

Community Perceptions of Specific Skin Features of Possible Melanoma

ERIC Educational Resources Information Center

Baade, Peter D.; Balanda, Kevin P.; Stanton, Warren R.; Lowe, John B.; Del Mar, Chris B.

2004-01-01

Background: Melanoma can be curable if detected early. One component of detecting melanoma is an awareness of the important features of the disease. It is currently not clear which features the community view as indicative of melanoma. Objective: To investigate which features of the skin members of an urban community believe may indicate skin…

Face Inversion Disproportionately Impairs the Perception of Vertical but Not Horizontal Relations between Features

ERIC Educational Resources Information Center

Goffaux, Valerie; Rossion, Bruno

2007-01-01

Upside-down inversion disrupts the processing of spatial relations between the features of a face, while largely preserving local feature analysis. However, recent studies on face inversion failed to observe a clear dissociation between relational and featural processing. To resolve these discrepancies and clarify how inversion affects face…

Quantification of nanoparticle endocytosis based on double fluorescent pH-sensitive nanoparticles.

PubMed

Kurtz-Chalot, Andréa; Klein, Jean-Philippe; Pourchez, Jérémie; Boudard, Delphine; Bin, Valérie; Sabido, Odile; Marmuse, Laurence; Cottier, Michèle; Forest, Valérie

2015-04-01

Amorphous silica is a particularly interesting material because of its inertness and chemical stability. Silica nanoparticles have been recently developed for biomedical purposes but their innocuousness must be carefully investigated before clinical use. The relationship between nanoparticles physicochemical features, their uptake by cells and their biological activity represents a crucial issue, especially for the development of nanomedicine. This work aimed at adapting a method for the quantification of nanoparticle endocytosis based on pH-sensitive and double fluorescent particles. For that purpose, silica nanoparticles containing two fluorophores: FITC and pHrodo(TM) were developed, their respective fluorescence emission depends on the external pH. Indeed, FITC emits a green fluorescence at physiological pH and pHrodo(TM) emits a red fluorescence which intensity increased with acidification. Therefore, nanoparticles remained outside the cells could be clearly distinguished from nanoparticles uptaken by cells as these latter could be spotted inside cellular acidic compartments (such as phagolysosomes, micropinosomes…). Using this model, the endocytosis of 60 nm nanoparticles incubated with the RAW 264.7 macrophages was quantified using time-lapse microscopy and compared to that of 130 nm submicronic particles. The amount of internalized particles was also evaluated by fluorimetry. The biological impact of the particles was also investigated in terms of cytotoxicity, pro-inflammatory response and oxidative stress. Results clearly demonstrated that nanoparticles were more uptaken and more reactive than submicronic particles. Moreover, we validated a method of endocytosis quantification.

Single-molecule RNA detection at depth by hybridization chain reaction and tissue hydrogel embedding and clearing.

PubMed

Shah, Sheel; Lubeck, Eric; Schwarzkopf, Maayan; He, Ting-Fang; Greenbaum, Alon; Sohn, Chang Ho; Lignell, Antti; Choi, Harry M T; Gradinaru, Viviana; Pierce, Niles A; Cai, Long

2016-08-01

Accurate and robust detection of mRNA molecules in thick tissue samples can reveal gene expression patterns in single cells within their native environment. Preserving spatial relationships while accessing the transcriptome of selected cells is a crucial feature for advancing many biological areas - from developmental biology to neuroscience. However, because of the high autofluorescence background of many tissue samples, it is difficult to detect single-molecule fluorescence in situ hybridization (smFISH) signals robustly in opaque thick samples. Here, we draw on principles from the emerging discipline of dynamic nucleic acid nanotechnology to develop a robust method for multi-color, multi-RNA imaging in deep tissues using single-molecule hybridization chain reaction (smHCR). Using this approach, single transcripts can be imaged using epifluorescence, confocal or selective plane illumination microscopy (SPIM) depending on the imaging depth required. We show that smHCR has high sensitivity in detecting mRNAs in cell culture and whole-mount zebrafish embryos, and that combined with SPIM and PACT (passive CLARITY technique) tissue hydrogel embedding and clearing, smHCR can detect single mRNAs deep within thick (0.5 mm) brain slices. By simultaneously achieving ∼20-fold signal amplification and diffraction-limited spatial resolution, smHCR offers a robust and versatile approach for detecting single mRNAs in situ, including in thick tissues where high background undermines the performance of unamplified smFISH. © 2016. Published by The Company of Biologists Ltd.

Primary mucoepidermoid carcinoma of the lung with prominent clear cells

PubMed Central

Fink, David D.; Lomas, Angela M.; Roden, Anja C.; Shah, Prashant C.

2017-01-01

Mucoepidermoid carcinoma of the lung is a rare malignancy of salivary gland-type origin. We report a case of a 21-year-old man with a right mainstem bronchus mass composed predominantly of clear cells. This case represents a rare primary pulmonary low-grade mucoepidermoid carcinoma positive for MAML2 rearrangement by fluorescence in situ hybridization with a prominent clear cell component. PMID:28670072

[Non-metastatic clear cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics].

PubMed

Iurin, A G

2010-01-01

Non-metastatic clear-cell renal cancer: dependence of the tumour stage on clinico-anatomic and morphologic factors; prognostic value of macro- and karyometric characteristics Sankt Peterburg Pathology Bureau, Sankt Peterburg It was shown based on multivariate regression analysis that pT1a3bN0MO stages of non-metastatic clear-cell renal cancer significantly correlate not only with the tumor size and invasion into the fatty tissue and/or renal vein but also with the invasion into the renal capsule and with the mean maximum diameter and mean nucleus area of tumor cells. There was no correlation of clear-cell renal cancer stages with tumor proliferative activity, gene p53 mutation, oncosuppressor gene PTEN expression, fraction of tumour clear-cell component, and such clinical characteristics as patients' sex, age, and body mass index. Taking into account statistically significant differences between the patients' survival rates, the regression equations developed in this work may be used for the prediction of disease outcome.

Exploring the retinal connectome

PubMed Central

Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

2011-01-01

Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices. Conclusions Connectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipolar cell networks and extensive photopic GABAergic amacrine cell inputs. Further, bipolar cells show extensive inputs and outputs along their axons, similar to multistratified nonmammalian bipolar cells. Physiologic evidence of significant ON-OFF channel crossover is strongly supported by our anatomic data, showing alternating glycine-to-GABA paths. Long chains of amacrine cell networks likely arise from homocellular GABAergic synapses between starburst amacrine cells. Deeper analysis of RC1 offers the opportunity for more complete descriptions of specific networks. PMID:21311605

Exploring the retinal connectome.

PubMed

Anderson, James R; Jones, Bryan W; Watt, Carl B; Shaw, Margaret V; Yang, Jia-Hui; Demill, David; Lauritzen, James S; Lin, Yanhua; Rapp, Kevin D; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross; Marc, Robert E

2011-02-03

A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈ 2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices. Connectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipolar cell networks and extensive photopic GABAergic amacrine cell inputs. Further, bipolar cells show extensive inputs and outputs along their axons, similar to multistratified nonmammalian bipolar cells. Physiologic evidence of significant ON-OFF channel crossover is strongly supported by our anatomic data, showing alternating glycine-to-GABA paths. Long chains of amacrine cell networks likely arise from homocellular GABAergic synapses between starburst amacrine cells. Deeper analysis of RC1 offers the opportunity for more complete descriptions of specific networks.

HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases.

PubMed

Appay, Romain; Macagno, Nicolas; Padovani, Laetitia; Korshunov, Andrey; Kool, Marcel; André, Nicolas; Scavarda, Didier; Pietsch, Torsten; Figarella-Branger, Dominique

2017-09-01

The central nervous system (CNS) high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR) is a recently described molecular entity. We report 3 new CNS HGNET-BCOR cases sharing common clinical presentation and pathologic features. The 3 cases concerned children aged 3 to 7 years who presented with a voluminous mass of the cerebellum. Pathologic features included proliferation of uniform spindle to ovoid cells with fine chromatin associated with a rich arborizing capillary network. Methylation profiling classified these cases as CNS HGNET-BCOR tumors. Polymerase chain reaction analysis confirmed the presence of internal tandem duplications in the C-terminus of BCOR (BCOR-ITD), a characteristic of these tumors, in all 3 cases. Immunohistochemistry showed a strong nuclear BCOR expression. In 2 cases, local recurrence occurred within 6 months. The third case, a patient who received a craniospinal irradiation after total surgical removal followed by a metronomics maintenance with irinotecan, temozolomide, and itraconazole, is still free of disease 14 months after diagnosis. In summary, CNS HGNET-BCOR represents a rare tumor occurring in young patients with dismal prognosis. BCOR nuclear immunoreactivity is highly suggestive of a BCOR-ITD. Whether CNS HGNET-BCOR should be classified among the category of "embryonal tumors" or within the category of "mesenchymal, nonmeningothelial tumors" remains to be clarified. Because CNS HGNET-BCOR share pathologic features and characteristic BCOR-ITD with clear cell sarcoma of the kidney, these tumors may represent local variants of the same entity.

Origin of clear cell carcinoma: nature or nurture?

PubMed

Kolin, David L; Dinulescu, Daniela M; Crum, Christopher P

2018-02-01

A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinomas suggest that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer. Cochrane and colleagues address this question in a recent article in this journal. They show that a marker of ovarian clear cell carcinoma, cystathionine gamma lyase, is expressed in ciliated cells. Similarly, they show that markers of secretory cells (estrogen receptor and methylenetetrahydrofolate dehydrogenase 1) are expressed in ovarian endometrioid carcinoma. Taken together, they suggest that endometrioid and clear cell carcinomas arise from cells related to secretory and ciliated cells, respectively. We discuss Cochrane et al's work in the context of other efforts to determine the cell of origin of gynecological malignancies, with an emphasis on recent developments and challenges unique to the area. These limitations complicate our interpretation of tumor differentiation; does it reflect nature imposed by a specific cell of origin or nurture, by either mutation(s) or environment? Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A huge malignant perivascular epithelioid cell tumor (PEComa) of the uterine cervix and vagina.

PubMed

Natella, Valentina; Merolla, Francesco; Giampaolino, Pierluigi; Bifulco, Giuseppe; Mainenti, Pier Paolo; Insabato, Luigi

2014-03-01

Perivascular epithelioid cell tumors (PEComas) are a family of rare mesenchymal neoplasms, including angiomyolipoma, clear-cell "sugar" tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear-cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and clear-cell tumors at various other anatomic sites. These tumors are characterized by a proliferation of epithelioid cells with clear to eosinophilic cytoplasm, perivascular distribution, and coexpression of myogenic and melanocytic markers. PEComas show a female predominance, occur with some frequency in the gynecological tract, and have an unpredictable biological behavior. We report a case of a huge malignant PEComa arising from the uterine cervix and vagina. To the best of our knowledge, only 6 cases of PEComa in the cervix and 2 cases in the vagina have been reported in the literature. Copyright © 2013 Elsevier GmbH. All rights reserved.

Exploring viral reservoir: The combining approach of cell sorting and droplet digital PCR.

PubMed

Gibellini, Lara; Pecorini, Simone; De Biasi, Sara; Pinti, Marcello; Bianchini, Elena; De Gaetano, Anna; Digaetano, Margherita; Pullano, Rosalberta; Lo Tartaro, Domenico; Iannone, Anna; Mussini, Cristina; Cossarizza, Andrea; Nasi, Milena

2018-02-01

Combined antiretroviral therapy (cART) blocks different steps of HIV replication and maintains plasma viral RNA at undetectable levels. The virus can remain in long-living cells and create a reservoir where HIV can restart replicating after cART discontinuation. A persistent viral production triggers and maintains a persistent immune activation, which is a well-known feature of chronic HIV infection, and contributes either to precocious aging, or to the increased incidence of morbidity and mortality of HIV positive patients. The new frontier of the treatment of HIV infection is nowadays eradication of the virus from all host cells and tissues. For this reason, it is crucial to have a clear and precise idea of where the virus hides, and which are the cells that keep it silent. Important efforts have been made to improve the detection of viral reservoirs, and new techniques are now giving the opportunity to characterize viral reservoirs. Among these techniques, a strategic approach based upon cell sorting and droplet digital PCR (ddPCR) is opening new horizons and opportunities of research. This review provides an overview of the methods that combine cell sorting and ddPCR for the quantification of HIV DNA in different cell types, and for the detection of its maintenance. Copyright © 2017 Elsevier Inc. All rights reserved.

CD8+ T Cell-Mediated Immunity during Trypanosoma cruzi Infection: A Path for Vaccine Development?

PubMed Central

dos Santos Virgilio, Fernando; Pontes, Camila; Dominguez, Mariana Ribeiro; Ersching, Jonatan; Rodrigues, Mauricio Martins; Vasconcelos, José Ronnie

2014-01-01

MHC-restricted CD8+ T cells are important during infection with the intracellular protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Experimental studies performed in the past 25 years have elucidated a number of features related to the immune response mediated by these T cells, which are important for establishing the parasite/host equilibrium leading to chronic infection. CD8+ T cells are specific for highly immunodominant antigens expressed by members of the trans-sialidase family. After infection, their activation is delayed, and the cells display a high proliferative activity associated with high apoptotic rates. Although they participate in parasite control and elimination, they are unable to clear the infection due to their low fitness, allowing the parasite to establish the chronic phase when these cells then play an active role in the induction of heart immunopathology. Vaccination with a number of subunit recombinant vaccines aimed at eliciting specific CD8+ T cells can reverse this path, thereby generating a productive immune response that will lead to the control of infection, reduction of symptoms, and reduction of disease transmission. Due to these attributes, activation of CD8+ T lymphocytes may constitute a path for the development of a veterinarian or human vaccine. PMID:25104879

Infrared and Visual Image Fusion through Fuzzy Measure and Alternating Operators

PubMed Central

Bai, Xiangzhi

2015-01-01

The crucial problem of infrared and visual image fusion is how to effectively extract the image features, including the image regions and details and combine these features into the final fusion result to produce a clear fused image. To obtain an effective fusion result with clear image details, an algorithm for infrared and visual image fusion through the fuzzy measure and alternating operators is proposed in this paper. Firstly, the alternating operators constructed using the opening and closing based toggle operator are analyzed. Secondly, two types of the constructed alternating operators are used to extract the multi-scale features of the original infrared and visual images for fusion. Thirdly, the extracted multi-scale features are combined through the fuzzy measure-based weight strategy to form the final fusion features. Finally, the final fusion features are incorporated with the original infrared and visual images using the contrast enlargement strategy. All the experimental results indicate that the proposed algorithm is effective for infrared and visual image fusion. PMID:26184229

Infrared and Visual Image Fusion through Fuzzy Measure and Alternating Operators.

PubMed

Bai, Xiangzhi

2015-07-15

The crucial problem of infrared and visual image fusion is how to effectively extract the image features, including the image regions and details and combine these features into the final fusion result to produce a clear fused image. To obtain an effective fusion result with clear image details, an algorithm for infrared and visual image fusion through the fuzzy measure and alternating operators is proposed in this paper. Firstly, the alternating operators constructed using the opening and closing based toggle operator are analyzed. Secondly, two types of the constructed alternating operators are used to extract the multi-scale features of the original infrared and visual images for fusion. Thirdly, the extracted multi-scale features are combined through the fuzzy measure-based weight strategy to form the final fusion features. Finally, the final fusion features are incorporated with the original infrared and visual images using the contrast enlargement strategy. All the experimental results indicate that the proposed algorithm is effective for infrared and visual image fusion.

Functions of TGF-β-exposed plasmacytoid dendritic cells.

PubMed

Saas, Philippe; Perruche, Sylvain

2012-01-01

Plasmacytoid dendritic cells (pDCs) belong to the family of dendritic cells and possess specific features that distinguish them from conventional dendritic cells. For instance, pDC are the main interferon-alpha-secreting cells. Plasmacytoid dendritic cells exert both proinflammatory and regulatory functions. This is attested by the involvement of pDC through interferon-alpha secretion in several autoimmune diseases, and by the implication of pDC in tolerance. The same is true for TGF-β that plays a dual role in inflammation. In this review, we discuss recent data on pDC and TGF-β interactions. As with many cell types, pDCs are able to respond to TGF-β using the classic Smad signaling pathway. In addition, pDCs are capable to secrete TGF-β, in particular in response to TGF-β exposure. Exposure of pDCs to TGF-β prevents type I interferon secretion in response to TLR7/9 ligands. In contrast, the consequences of TGF-β on the antigen-presenting cell capacities of pDC are less clear, since TGF-β-exposed pDCs may lead to both regulatory T-cell and interleukin-17-secreting cell polarization. Here, we discuss the factors that may influence this polarization. We also discuss how pDCs exposed to TGF-β may participate in tolerance induction and maintenance, or, on the contrary, in autoimmune diseases.

Clear cell carcinoma of the ovary mimicking struma ovarii and carcinoid tumor.

PubMed

Alduaij, Ahmad; Quddus, M Ruhul

2011-04-01

Clear cell carcinomas are considered as high-grade tumor often with poor prognosis. We describe 2 cases of clear cell carcinomas of the ovary mimicking benign or less aggressive tumors encountered in the female genital track. The first case is mimicking a benign monodermal teratoma, the so-called struma ovarii, and the second mimicking a carcinoid tumor. Copyright © 2011 Elsevier Inc. All rights reserved.

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Helminth immunoregulation: The role of parasite secreted proteins in modulating host immunity

PubMed Central

Hewitson, James P.; Grainger, John R.; Maizels, Rick M.

2009-01-01

Helminths are masterful immunoregulators. A characteristic feature of helminth infection is a Th2-dominated immune response, but stimulation of immunoregulatory cell populations, such as regulatory T cells and alternatively activated macrophages, is equally common. Typically, Th1/17 immunity is blocked and productive effector responses are muted, allowing survival of the parasite in a “modified Th2” environment. Drug treatment to clear the worms reverses the immunoregulatory effects, indicating that a state of active suppression is maintained by the parasite. Hence, research has focussed on “excretory–secretory” products released by live parasites, which can interfere with every aspect of host immunity from initial recognition to end-stage effector mechanisms. In this review, we survey our knowledge of helminth secreted molecules, and summarise current understanding of the growing number of individual helminth mediators that have been shown to target key receptors or pathways in the mammalian immune system. PMID:19406170

Parametric imaging of clear cell and papillary renal cell carcinoma using contrast-enhanced ultrasound (CEUS).

PubMed

Rübenthaler, J; Reimann, R; Hristova, P; Staehler, M; Reiser, M; Clevert, D A

2015-10-16

The aim of this study was to analyse clear cell and papillary renal cell carcinoma (RCC) examined with contrast-enhanced ultrasound (CEUS) and a second generation blood pool agent (SonoVue®, Bracco, Milan, Italy) before clinical intervention. A total of 41 patients with histologically proven subtypes of RCC were examined. 29 patients had a clear cell RCC and 12 patients showed a papillary RCC. Average size in the clear cell RCC group was 6.07 cm and 1.88 cm in the papillary RCC group. An experienced radiologist examined all patients with CEUS. The following parameters were analysed: maximum signal intensity (PEAK), time elapsed until PEAK is reached (MTT), local blood flow (RBF), area under the time intensity curve (AUC) and the signal intensity (SI) during the course of time. For both groups all comparisons were made based on healthy renal parenchyma. In the clear cell RCC significant differences (significance level p < 0.05) between cancerous tissue and the healthy renal parenchyma were noticed in all four parameters. The clear cell RCC showed a significant reduced blood volume. It reached the PEAK reading relatively rapidly and its signal intensity was always lower than that of the healthy renal parenchyma. In the arterial phase retarded absorption of the contrast agent was observed, followed by fast washing out of the contrast agent bubbles.In the papillary RCC group, significant findings as to PEAK and RBF as well as a slightly significant difference as to AUC were recorded. The papillary RCC had a lower blood supply and reached its PEAK reading later. Its signal intensity was also reduced. The signal intensity of papillary NCC was significantly lower compared with clear cell RCC; absorption and washing out of the contrast agent was delayed. CEUS seems to be an useful additional method to clinically differentiate between clear cell and papillary RCC. In daily clinical use, patients with contraindication for other imaging methods, especially the magnetic resonance imaging, might particularly benefit from this method.

The effects of organophosphorus insecticides and heavy metals on DNA damage and programmed cell death in two plant models.

PubMed

Cortés-Eslava, Josefina; Gómez-Arroyo, Sandra; Risueño, Maria C; Testillano, Pilar S

2018-05-02

The ubiquity of pollutants, such as agrochemicals and heavy metals, constitute a serious risk to human health. To evaluate the induction of DNA damage and programmed cell death (PCD), root cells of Allium cepa and Vicia faba were treated with two organophosphate insecticides (OI), fenthion and malathion, and with two heavy metal (HM) salts, nickel nitrate and potassium dichromate. An alkaline variant of the comet assay was performed to identify DNA breaks; the results showed comets in a dose-dependent manner, while higher concentrations induced clouds following exposure to OIs and HMs. Similarly, treatments with higher concentrations of OIs and HMs were analyzed by immunocytochemistry, and several structural characteristics of PCD were observed, including chromatin condensation, cytoplasmic vacuolization, nuclear shrinkage, condensation of the protoplast away from the cell wall, and nuclei fragmentation with apoptotic-like corpse formation. Abiotic stress also caused other features associated with PCD, such as an increase of active caspase-3-like protein, changes in the location of cytochrome C (Cyt C) toward the cytoplasm, and decreases in extracellular signal-regulated protein kinase (ERK) expression. Genotoxicity results setting out an oxidative via of DNA damage and evidence the role of the high affinity of HM and OI by DNA molecule as underlying cause of genotoxic effect. The PCD features observed in root cells of A. cepa and V. faba suggest that PCD takes place through a process that involves ERK inactivation, culminating in Cyt C release and caspase-3-like activation. The sensitivity of both plant models to abiotic stress was clearly demonstrated, validating their role as good biosensors of DNA breakage and PCD induced by environmental stressors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epigenome overlap measure (EPOM) for comparing tissue/cell types based on chromatin states.

PubMed

Li, Wei Vivian; Razaee, Zahra S; Li, Jingyi Jessica

2016-01-11

The dynamics of epigenomic marks in their relevant chromatin states regulate distinct gene expression patterns, biological functions and phenotypic variations in biological processes. The availability of high-throughput epigenomic data generated by next-generation sequencing technologies allows a data-driven approach to evaluate the similarities and differences of diverse tissue and cell types in terms of epigenomic features. While ChromImpute has allowed for the imputation of large-scale epigenomic information to yield more robust data to capture meaningful relationships between biological samples, widely used methods such as hierarchical clustering and correlation analysis cannot adequately utilize epigenomic data to accurately reveal the distinction and grouping of different tissue and cell types. We utilize a three-step testing procedure-ANOVA, t test and overlap test to identify tissue/cell-type- associated enhancers and promoters and to calculate a newly defined Epigenomic Overlap Measure (EPOM). EPOM results in a clear correspondence map of biological samples from different tissue and cell types through comparison of epigenomic marks evaluated in their relevant chromatin states. Correspondence maps by EPOM show strong capability in distinguishing and grouping different tissue and cell types and reveal biologically meaningful similarities between Heart and Muscle, Blood & T-cell and HSC & B-cell, Brain and Neurosphere, etc. The gene ontology enrichment analysis both supports and explains the discoveries made by EPOM and suggests that the associated enhancers and promoters demonstrate distinguishable functions across tissue and cell types. Moreover, the tissue/cell-type-associated enhancers and promoters show enrichment in the disease-related SNPs that are also associated with the corresponding tissue or cell types. This agreement suggests the potential of identifying causal genetic variants relevant to cell-type-specific diseases from our identified associated enhancers and promoters. The proposed EPOM measure demonstrates superior capability in grouping and finding a clear correspondence map of biological samples from different tissue and cell types. The identified associated enhancers and promoters provide a comprehensive catalog to study distinct biological processes and disease variants in different tissue and cell types. Our results also find that the associated promoters exhibit more cell-type-specific functions than the associated enhancers do, suggesting that the non-associated promoters have more housekeeping functions than the non-associated enhancers.

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

ClinicalTrials.gov

2018-02-05

Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

Immunoliposomal delivery of doxorubicin can overcome multidrug resistance mechanisms in EGFR-overexpressing tumor cells.

PubMed

Mamot, Christoph; Ritschard, Reto; Wicki, Andreas; Küng, Willy; Schuller, Jan; Herrmann, Richard; Rochlitz, Christoph

2012-06-01

Immunoliposomes (ILs) can be constructed to target the epidermal growth factor receptor (EGFR) to provide efficient intracellular drug delivery in tumor cells. We hypothesized that this approach might be able to overcome drug resistance mechanisms, which remain an important obstacle to better outcomes in cancer therapy. ILs were evaluated in vitro and in vivo against EGFR-overexpressing pairs of human cancer cells (HT-29 and MDA-MB-231) that either lack or feature the multidrug resistance (mdr) phenotype. In multidrug-resistant cell lines, ILs loaded with doxorubicin (DOX) produced 19-216-fold greater cytotoxicity than free DOX, whereas in nonresistant cells, immunoliposomal cytotoxicity of DOX was comparable with that of the free drug. In intracellular distribution studies, free DOX was efficiently pumped out of the multidrug-resistant tumor cells, whereas immunoliposomal DOX leads to 3.5-8 times higher accumulation of DOX in the cytoplasm and 3.5-4.9 times in the nuclei compared with the free drug. Finally, in vivo studies in the MDA-MB-231 Vb100 xenograft model confirmed the ability of anti-EGFR ILs-DOX to efficiently target multidrug-resistant cells and showed impressive antitumor effects, clearly superior to all other treatments. In conclusion, ILs provide efficient and targeted drug delivery to EGFR-overexpressing tumor cells and are capable of completely reversing the multidrug-resistant phenotype of human cancer cells.

Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids.

PubMed

Schmitz, Alexander; Fischer, Sabine C; Mattheyer, Christian; Pampaloni, Francesco; Stelzer, Ernst H K

2017-03-03

Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid's size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 10 5 to 1 × 10 6  cells/mm 3 . Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.

Structural and functional characterization of the protein kinase Mps1 in Arabidopsis thaliana.

PubMed

de Oliveira, Eduardo Alves Gamosa; Romeiro, Nelilma Correia; Ribeiro, Elane da Silva; Santa-Catarina, Claudete; Oliveira, Antônia Elenir Amâncio; Silveira, Vanildo; de Souza Filho, Gonçalo Apolinário; Venancio, Thiago Motta; Cruz, Marco Antônio Lopes

2012-01-01

In eukaryotes, protein kinases catalyze the transfer of a gamma-phosphate from ATP (or GTP) to specific amino acids in protein targets. In plants, protein kinases have been shown to participate in signaling cascades driving responses to environmental stimuli and developmental processes. Plant meristems are undifferentiated tissues that provide the major source of cells that will form organs throughout development. However, non-dividing specialized cells can also dedifferentiate and re-initiate cell division if exposed to appropriate conditions. Mps1 (Monopolar spindle) is a dual-specificity protein kinase that plays a critical role in monitoring the accuracy of chromosome segregation in the mitotic checkpoint mechanism. Although Mps1 functions have been clearly demonstrated in animals and fungi, its role in plants is so far unclear. Here, using structural and biochemical analyses here we show that Mps1 has highly similar homologs in many plant genomes across distinct lineages (e.g. AtMps1 in Arabidopsis thaliana). Several structural features (i.e. catalytic site, DFG motif and threonine triad) are clearly conserved in plant Mps1 kinases. Structural and sequence analysis also suggest that AtMps1 interact with other cell cycle proteins, such as Mad2 and MAPK1. By using a very specific Mps1 inhibitor (SP600125) we show that compromised AtMps1 activity hampers the development of A. thaliana seedlings in a dose-dependent manner, especially in secondary roots. Moreover, concomitant administration of the auxin IAA neutralizes the AtMps1 inhibition phenotype, allowing secondary root development. These observations let us to hypothesize that AtMps1 might be a downstream regulator of IAA signaling in the formation of secondary roots. Our results indicate that Mps1 might be a universal component of the Spindle Assembly Checkpoint machinery across very distant lineages of eukaryotes.

PBRM1 and VHL expression correlate in human clear cell renal cell carcinoma with differential association with patient's overall survival.

PubMed

Högner, Anica; Krause, Hans; Jandrig, Burkhard; Kasim, Mumtaz; Fuller, Tom Florian; Schostak, Martin; Erbersdobler, Andreas; Patzak, Andreas; Kilic, Ergin

2018-03-01

To identify the clinicopathological association of PBRM1 (Polybromo-1 gene) and VHL (von Hippel-Lindau gene) expression at mRNA and protein levels in clear cell renal cell carcinoma (ccRCC) and its role in tumor progression. Immunohistochemical analysis, Western blotting and qPCR analysis of PBRM1 and VHL were performed on fresh-frozen ccRCC and adjacent normal tissue obtained from 70 patients who underwent radical nephrectomy. In addition, a tissue microarray (TMA) from specimens of 326 ccRCC patients was used to evaluate the effect of loss of PBRM1 and VHL immunohistological expression on clinicopathological features as well as patient survival. In frozen tissue, PBRM1 and VHL mRNA were significantly down-regulated in most ccRCC tumors (77.6%/80.6%). Simultaneous weak PBRM1 and VHL protein expression was observed in 21.4% of frozen tumors. In the TMA samples, weak PBRM1 and VHL immunohistochemical staining was observed in 60.4% of the cases and was correlated (P<0.001). The association of PBRM1 and VHL immunohistochemical expression with clinicopathological parameters depicts a variable picture: predominantly weak PBRM1 and VHL expression were significantly associated with higher Fuhrman grade (P = 0.012 and 0.024, respectively) but only weak VHL expression was associated with a higher pT stage (P = 0.023). PBRM1 expression did not affect the overall survival, whereas weak VHL expression was associated with decreased patient overall survival (P = 0.013). Our data suggest that reduced expression of PBRM1 and VHL is correlated with an increased tumor aggressiveness. Low VHL expression was identified as a risk factor for worse patient overall survival, independently from PBRM1 expression pattern. Copyright © 2018 Elsevier Inc. All rights reserved.

Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

PubMed

Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

2017-03-01

Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

Hilar fat infiltration: A new prognostic factor in metastatic clear cell renal cell carcinoma with first-line sunitinib treatment.

PubMed

Kammerer-Jacquet, Solène-Florence; Brunot, Angelique; Bensalah, Karim; Campillo-Gimenez, Boris; Lefort, Mathilde; Bayat, Sahar; Ravaud, Alain; Dupuis, Frantz; Yacoub, Mokrane; Verhoest, Gregory; Peyronnet, Benoit; Mathieu, Romain; Lespagnol, Alexandra; Mosser, Jean; Edeline, Julien; Laguerre, Brigitte; Bernhard, Jean-Christophe; Rioux-Leclercq, Nathalie

2017-10-01

The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib. In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect. HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival. HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Pigmented perivascular epithelioid cell tumor of the liver: report of a rare case with brief review of literature.

PubMed

Patra, Susama; Vij, Mukul; Kota, Venugopal; Kancherla, Ravindranath; Rela, Mohamed

2013-01-01

The perivascular epithelioid cell tumor (PEComa) family of tumors includes angiomyolipoma, lymphangioleiomyomatosis, clear cell sugar tumor of the lung, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomical sites (PEComas-NOS). Among the PEComas-NOS, pigmented variants are extremely rare. The case concerns a 50-year-old female who presented with pain in right hypochondrium. The resected specimen included a 24 × 18 × 9 cm mass. The tumor was histologically characterized by both spindle and epithelioid cells with round to oval nuclei and clear to eosinophilic cytoplasm containing abundant melanin pigment. The stroma demonstrated intervening, thin, fibrovascular septa. Immunohistochemically, the tumor cells were strongly positive for HMB-45, weak positive for smooth muscle actin (SMA), and negative for Hep Par 1, Glypican 3, MUM-1, and S-100 protein. The patient had no evidence of disease 24 months after surgery. Pathologists and clinicians should know about the existence of pigmented perivascular epithelioid cell tumor of the liver.

ABCD syndrome is caused by a homozygous mutation in the EDNRB gene.

PubMed

Verheij, Joke B G M; Kunze, Jürgen; Osinga, Jan; van Essen, Anthonie J; Hofstra, Robert M W

2002-03-15

ABCD syndrome is an autosomal recessive syndrome characterized by albinism, black lock, cell migration disorder of the neurocytes of the gut (Hirschsprung disease [HSCR]), and deafness. This phenotype clearly overlaps with the features of the Shah-Waardenburg syndrome, comprising sensorineural deafness; hypopigmentation of skin, hair, and irides; and HSCR. Therefore, we screened DNA of the index patient of the ABCD syndrome family for mutations in the endothelin B receptor (EDNRB) gene, a gene known to be involved in Shah-Waardenburg syndrome. A homozygous nonsense mutation in exon 3 (R201X) of the EDNRB gene was found. We therefore suggest that ABCD syndrome is not a separate entity, but an expression of Shah-Waardenburg syndrome.

Lung cancer progression and metastasis from the prognostic point of view.

PubMed

Inamura, Kentaro; Ishikawa, Yuichi

2010-08-01

Lung cancer is the leading cause of cancer death in men and women worldwide. Since the occurrence of metastases in distant organs is the major reason for mortality of cancer patients, we need to elucidate the underlying mechanisms. Many studies featuring analysis of gene expression, comparative genomic hybridization and loss of heterozygosity analysis have been performed and generated support for the hypothesis that metastatic potential is acquired early in tumorigenesis. Furthermore, it is now clear that the majority of tumor cells have the potential to metastasize. Although many changes in gene expression profiles have been established retrospectively, translational research is now a high priority to enable clinical application and treatment based on laboratory findings.

Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Theiler, James; Yoon, Hyejin; Yusim, Karina

Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraphmore » was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).« less

Three-dimensional ultrastructure of the surface of the tongue of the rat snake, Elaphe climacophora.

PubMed

Iwasaki, S; Yoshizawa, H; Kawahara, I

1996-05-01

Many studies have been performed to clarify the relationship between behavioral performance of the tongue and Jacobson's organ. The purpose of the present study was to examine the ultrastructural features of the surface of the tongue of the rat snake, Elaphe climacophora, and to delineate the functional relationship between the tongue and Jacobson's organ from a morphological perspective. The three-dimensional ultrastructure of the surface of the tongue of the rat snake Elaphe climacophora was investigated by scanning electron microscopy. Most of the surface of the bifurcated apex of the tongue was relatively smooth. Dome-shaped, hemispherical bulges or microfacets were compactly arranged on the epithelial cell surface over this entire region. Intercellular borders were clearly recognizable as striations. These features were almost the same as those of the dorsal surface of the transitional area between the bifurcated lingual apex and the anterior part of the lingual body. In the posterior half of the lingual body, no microfacets were seen at all. Both microridges and microvilli were compactly distributed on cell surfaces. No evidence was obtained from our ultrastructural analysis for an important role of the lingual apex in the vomeronasal system. By contrast, the epithelial surface of the body of the tongue appeared suitable for retaining stimulating compounds.

Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine

DOE PAGES

Theiler, James; Yoon, Hyejin; Yusim, Karina; ...

2016-10-05

Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraphmore » was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).« less

Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells.

PubMed

Jiménez-Heffernan, José A; Adrados, Magdalena; Muñoz-Hernández, Patricia; Fernández-Rico, Paloma; Ballesteros-García, Ana I; Fraga, Javier

2018-01-01

Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear. A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised. Needle aspiration revealed abundant neoplastic single cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells were also present. Nuclei of OGCs were monomorphic with oval morphology and were smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-, Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive behavior with further metastases to the axillary lymph nodes and oral cavity. Numerous OGCs are a rare and relevant finding in malignant melanoma. Their presence should not induce confusion with other tumors rich in osteoclastic cells. Since a relevant number of OGCs in melanoma may mean a more aggressive behavior, and patients may benefit from specific treatments, their presence should be mentioned in the pathologic report. © 2018 S. Karger AG, Basel.

Bridging the gap: from 2D cell culture to 3D microengineered extracellular matrices

PubMed Central

Li, Yanfen

2016-01-01

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we will explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, we will review the maturation of micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues. PMID:26592366

Identification of Novel Pro-Migratory, Cancer-Associated Genes Using Quantitative, Microscopy-Based Screening

PubMed Central

Naffar-Abu-Amara, Suha; Shay, Tal; Galun, Meirav; Cohen, Naomi; Isakoff, Steven J.; Kam, Zvi; Geiger, Benjamin

2008-01-01

Background Cell migration is a highly complex process, regulated by multiple genes, signaling pathways and external stimuli. To discover genes or pharmacological agents that can modulate the migratory activity of cells, screening strategies that enable the monitoring of diverse migratory parameters in a large number of samples are necessary. Methodology In the present study, we describe the development of a quantitative, high-throughput cell migration assay, based on a modified phagokinetic tracks (PKT) procedure, and apply it for identifying novel pro-migratory genes in a cancer-related gene library. In brief, cells are seeded on fibronectin-coated 96-well plates, covered with a monolayer of carboxylated latex beads. Motile cells clear the beads, located along their migratory paths, forming tracks that are visualized using an automated, transmitted-light screening microscope. The tracks are then segmented and characterized by multi-parametric, morphometric analysis, resolving a variety of morphological and kinetic features. Conclusions In this screen we identified 4 novel genes derived from breast carcinoma related cDNA library, whose over-expression induces major alteration in the migration of the stationary MCF7 cells. This approach can serve for high throughput screening for novel ways to modulate cellular migration in pathological states such as tumor metastasis and invasion. PMID:18213366

Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2018-06-06

Clear Cell Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Mucinous Adenocarcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Clear cell hidradenocarcinoma of the eyelid: a case report with a review of the literature.

PubMed

Singh, Gurcharan; Narasimha, Aparna; Kumar, Harendra; Datti, Narendra

2013-04-01

Clear cell hidradenocarcinomas are extremely rare neoplasms, with very few well-documented cases reported in the literature. The most common sites are the head and neck regions. These tumors are histologically malignant but are not always aggressive. They are known for recurrence and may metastasize widely. Treatment is wide local resection. We report on a case of clear cell hidradenocarcinoma occurring over the eyelid together with a review of the literature.

Understanding pathogenetic aspects and clinical presentation of primary effusion lymphoma (PEL) through its derived cell lines

PubMed Central

Carbone, Antonino; Cesarman, Ethel; Gloghini, Annunziata; Drexler, Hans G.

2013-01-01

Primary effusion lymphoma (PEL) is a very rare subgroup of B-cell lymphomas presenting as pleural, peritoneal and pericardial neoplastic effusions in the absence of a solid tumor mass or recognizable nodal involvement. There is strong evidence that Kaposi’s sarcoma associated herpesvirus (KSHV) is a causal agent of PEL. PEL tumor cells are latently infected by KSHV with consistent expression of several viral proteins and microRNAs that can affect cellular proliferation, differentiation and survival. The most relevant data on pathogenesis and biology of KSHV have been provided by studies on PEL derived cell lines. Fourteen continuous cell lines have been established from the malignant effusions of patients with AIDS-and non-AIDS-associated PEL. These KSHV+ EBV+/− cell lines are wellcharacterized, authenticated and mostly available from public biological ressource centers. The PEL cell lines display unique features and are clearly distinct from other lymphoma cell lines. PEL cell lines represent an indispensable tool for the understanding of KSHV biology and its impact on the clinical manifestation of PEL. Studies on PEL cell lines have shown that a number of viral genes, expressed during latency or lytic life cycle, have effects on cell binding, proliferation, angiogenesis and inflammation. Also PEL cell lines are important model systems for the study of the pathology of PEL including the lack of invasive or destructive growth patterns and the peculiar propensity of PEL to involve body cavity surfaces. PMID:20051807

Structural characteristics of Tla products

PubMed Central

1985-01-01

Biochemical study of thymus leukemia antigen (TL) from thymocytes of various Tla genotypes and from leukemia cells revealed features that, given present evidence, are peculiar to TL among class I products of the H-2:Qa:Tla region of chromosome 17. Sodium dodecyl sulfate- polyacrylamide gel electrophoresis (SDS-PAGE) of TL from thymocytes of all TL+ mouse strains, precipitated by anti-TL antiserum or monoclonal antibodies, showed two closely migrating bands of equal intensity in the heavy (H) chain position (45-50,000 mol wt). Comparison of these two bands by two-dimensional isoelectric focusing (2D IEF)-SDS-PAGE and 2D chymotryptic peptide mapping showed no differences indicative of protein dissimilarity. Thus, the two components of the H chain doublet may differ only in a feature of glycosylation that does not affect charge. The two leukemias studied gave only a single band in the H chain position. On 2D peptide mapping and 2D IEF-SDS-PAGE, the patterns for TL of Tlaa and Tlae thymocytes, which are closely related serologically, were broadly similar, but clearly different from the pattern typical of Tlac and Tlad thymocytes. 2D peptide maps of TL from Tlaa thymocytes and Tlaa leukemia cells did not differ. Leukemia cells of Tlab origin (thymocytes TL-) gave 2D peptide and 2D IEF-SDS-PAGE patterns of a third type. With the exception of Tlaa, thymocytes of TL+ mice yielded additional TL products of higher molecular weight than the TL H chain. PMID:3875681

Excitons in one-dimensional van der Waals materials: Sb2S3 nanoribbons

NASA Astrophysics Data System (ADS)

Caruso, Fabio; Filip, Marina R.; Giustino, Feliciano

2015-09-01

Antimony sulphide Sb2S3 has emerged as a promising material for a variety of energy applications ranging from solar cells to thermoelectrics and solid-state batteries. The most distinctive feature of Sb2S3 is its crystal structure, which consists of parallel 1-nm-wide ribbons held together by weak van der Waals forces. This structure clearly suggests that it should be possible to isolate individual Sb2S3 ribbons using micromechanical or liquid-phase exfoliation techniques. However, it is not clear yet how to identify the ribbons postexfoliation using standard optical probes. Using state-of-the-art first-principles calculations based on many-body perturbation theory, here we show that individual ribbons of Sb2S3 carry optical signatures clearly distinct from those of bulk Sb2S3 . In particular, we find a large blueshift of the optical absorption edge (from 1.38 to 2.30 eV) resulting from the interplay between a reduced screening and the formation of bound excitons. In addition, we observe a transition from an indirect band gap to a direct gap, suggesting an enhanced photoluminescence in the green. These unique fingerprints will enable extending the research on van der Waals materials to the case of one-dimensional chalchogenides.

The Harderian gland, its secretory duct and porphyrin content in the woodmouse (Apodemus sylvaticus).

PubMed Central

Johnston, H S; McGadey, J; Payne, A P; Thompson, G G; Moore, M R

1987-01-01

The Harderian gland of the woodmouse (Apodemus sylvaticus) consists of tubules lined by a single layer of epithelial cells with a surrounding layer of myoepithelial cells. The epithelium contains two cell types, one with numerous small, clear, lipid vacuoles (Type I), the other with large electron-dense ones (Type II). Each type is further subdivided into cells where the smooth endoplasmic reticulum exhibits pronounced vacuolation (Ia and IIa). The lipid vacuoles frequently coalesce and are released by exocytosis. They possess a multilamellar cap; similar multilamellar whorls (without a vacuole) are also seen. Polytubular complexes are a feature of Type II cells; tubules are in continuity with the smooth endoplasmic reticulum. Peroxisomes are also present. Fenestrated capillaries occur frequently in the interstitium, and (where no myoepithelial cell intervenes) the basal surface of the gland epithelial cell is covered with microvilli. There is no morphologically distinct duct system within the gland. The extraglandular duct is lined by columnar epithelium except at the opening on to the nictitating membrane where there is stratified squamous epithelium, with melanocytes and nests of mucus-secreting cells. The porphyrin content of the gland is low and solid intraluminal deposits are not seen. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:3429316

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques.

PubMed

Xavier, Miguel; Oreffo, Richard O C; Morgan, Hywel

2016-01-01

Skeletal stem cells (SSC) are a sub-population of bone marrow stromal cells that reside in postnatal bone marrow with osteogenic, chondrogenic and adipogenic differentiation potential. SSCs reside only in the bone marrow and have organisational and regulatory functions in the bone marrow microenvironment and give rise to the haematopoiesis-supportive stroma. Their differentiation capacity is restricted to skeletal lineages and therefore the term SSC should be clearly distinguished from mesenchymal stem cells which are reported to exist in extra-skeletal tissues and, critically, do not contribute to skeletal development. SSCs are responsible for the unique regeneration capacity of bone and offer unlimited potential for application in bone regenerative therapies. A current unmet challenge is the isolation of homogeneous populations of SSCs, in vitro, with homogeneous regeneration and differentiation capacities. Challenges that limit SSC isolation include a) the scarcity of SSCs in bone marrow aspirates, estimated at between 1 in 10-100,000 mononuclear cells; b) the absence of specific markers and thus the phenotypic ambiguity of the SSC and c) the complexity of bone marrow tissue. Microfluidics provides innovative approaches for cell separation based on bio-physical features of single cells. Here we review the physical principles underlying label-free microfluidic sorting techniques and review their capacity for stem cell selection/sorting from complex (heterogeneous) samples. Copyright © 2016 Elsevier Inc. All rights reserved.

6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition.

PubMed

Nedungadi, Divya; Binoy, Anupama; Pandurangan, Nanjan; Pal, Sanjay; Nair, Bipin G; Mishra, Nandita

2018-03-15

An α, β-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB-231) and non-small lung cancer (A549) cells. In the presence of autophagic inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death clearly distinguishing it from the classic autophagic process. 6S induced death did not exhibit the characteristic apoptotic features like caspase cleavage, phosphatidyl serine exposure and DNA fragmentation. The immunofluorescence with the Endoplasmic Reticulum (ER) resident protein, calreticulin indicated that the vacuoles were of ER origin, typical of paraptosis. This was supported by the increase in level of microtubule associated protein light chain 3B (LC3 I and LC3 II) and polyubiquitin binding protein, p62. The level of ER stress markers like polyubiquitinated proteins, Bip and CHOP also consistently increased. We have found that 6S inhibits the 26S proteasome. The proteasomal inhibitory activity was elucidated by a) molecular docking of 6S onto the active site of β5 subunit and b) reduced fluorescence by the fluorogenic substrate of the chymotrypsin-like subunit. In conclusion these studies demonstrate for the first time that proteasomal inhibition by 6S induces cell death via paraptosis. So 6-shogaol may act as a template for anti-cancer lead discovery against the apoptosis resistant cancer cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Primary clear cell carcinoma of parotid gland: Case report and review of literature.

PubMed

Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

2013-01-01

Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult.

Primary clear cell carcinoma of parotid gland: Case report and review of literature

PubMed Central

Rodríguez, Marta Saldaña; Reija, Maria Fe García; Rodilla, Irene González

2013-01-01

Clear cell carcinoma (CCC) is a rare low-grade carcinoma that represents only 1% to 2% of all salivary glands tumors. The finding of a clear cell tumor in a parotid gland involves the necessity of differential diagnosis between primary clear cell parotid tumors and metastases, mainly from kidney. The biological behavior is not very aggressive and development, which is very slow, is usually asymptomatic and indeed, the tumor often reaches considerable dimensions before being diagnosed. The treatment of choice is the surgical excision. There are rare cases of local recurrence and distant metastases. The aim of this article is to report a primary CCC in the parotid gland that microscopically closely resembled a metastatic CCC of renal origin, making microscopic differentiation difficult. PMID:23798840

A home away from home: challenges and opportunities in engineering in vitro muscle satellite cell niches

PubMed Central

Cosgrove, Benjamin D.; Sacco, Alessandra; Gilbert, Penney M.; Blau, Helen M.

2009-01-01

Satellite cells are skeletal muscle stem cells with a principal role in postnatal skeletal muscle regeneration. Satellite cells, like many tissue-specific adult stem cells, reside in a quiescent state in an instructive, anatomically defined niche. The satellite cell niche constitutes a distinct membrane-enclosed compartment within the muscle fiber, containing a diversity of biochemical and biophysical signals that influence satellite cell function. A major limitation to the study and clinical utility of satellite cells is that upon removal from the muscle fiber and plating in traditional plastic tissue culture platforms, their muscle stem cell properties are rapidly lost. Clearly, the maintenance of stem cell function is critically dependent on in vivo niche signals, highlighting the need to create novel in vitro microenvironments that allow for the maintenance and propagation of satellite cells while retaining their potential to function as muscle stem cells. Here, we discuss how emerging biomaterials technologies offer great promise for engineering in vitro microenvironments to meet these challenges. In engineered biomaterials, signaling molecules can be presented in a manner that more closely mimics cell-cell and cell-matrix interactions and matrices can be fabricated with diverse rigidities that approximate in vivo tissues. The development of in vitro microenvironments in which niche features can be systematically modulated will be instrumental not only to future insights into muscle stem cell biology and therapeutic approaches to muscle diseases and muscle wasting with aging, but also will provide a paradigm for the analysis of numerous adult tissue-specific stem cells. PMID:19751902

High throughput parallel backside contacting and periodic texturing for high-efficiency solar cells

DOEpatents

Daniel, Claus; Blue, Craig A.; Ott, Ronald D.

2014-08-19

Disclosed are configurations of long-range ordered features of solar cell materials, and methods for forming same. Some features include electrical access openings through a backing layer to a photovoltaic material in the solar cell. Some features include textured features disposed adjacent a surface of a solar cell material. Typically the long-range ordered features are formed by ablating the solar cell material with a laser interference pattern from at least two laser beams.

Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway Regulated-Circulating microRNA

DTIC Science & Technology

2016-05-01

Award Number: W81XWH-11-1-0715 TITLE: Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-Regulated Circulating microRNA PRINCIPAL...TITLE AND SUBTITLE Sa. CONTRACT NUMBER Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway- Regulated Circulating microRNA Sb. GRANT NUMBER...panel of diagnostic miRNAs that are measurable in serum and will be able to identify kidney cancer in its earliest stages. We hypothesized that serum

Clear-Cell Meningioma: CT and MR Imaging Findings in Two Cases Involving the Spinal Canal and Cerebellopontine Angle

PubMed Central

Yu, Ki Bong; Kim, Hyung Jin; Suh, Chang Hae; Park, Hyung Chun; Kim, Eun Young; Han, Hye Seung

2002-01-01

Clear-cell meningioma is a rare subtype of meningioma which occurs at a younger age and has a higher recurrence rate than other subtypes. We report two cases of clear-cell meningioma, one in the thoracolumbar spinal canal and the other in the cerebellopontine angle. Though the CT and MR imaging findings were not different from those of ordinary meningioma, after surgical removal the condition recurred repeatedly in the patient with spinal canal involvement. PMID:12087202

Various clinical application of phase contrast X-ray

NASA Astrophysics Data System (ADS)

Oh, Chilhwan; Park, Sangyong; Ha, Seunghan; Park, Gyuman; Lee, Gunwoo; Lee, Onseok; Je, Jungho

2008-02-01

In biomedical application study using phase contrast X-ray, both sample thickness or density and absorption difference are very important factors in aspects of contrast enhancement. We present experimental evidence that synchrotron hard X-ray are suitable for radiological imaging of biological samples down to the cellular level. We investigated the potential of refractive index radiology using un-monochromatized synchrotron hard X-rays for the imaging of cell and tissue in various diseases. Material had been adopted various medical field, such as apoE knockout mouse in cardiologic field, specimen from renal and prostatic carcinoma patient in urology, basal cell epithelioma in dermatology, brain tissue from autosy sample of pakinson's disease, artificially induced artilrtis tissue from rabbits and extracted tooth from patients of crack tooth syndrome. Formalin and paraffin fixed tissue blocks were cut in 3 mm thickness for the X-ray radiographic imaging. From adjacent areas, 4 μm thickness sections were also prepared for hematoxylin-eosin staining. Radiographic images of dissected tissues were obtained using the hard X-rays from the 7B2 beamline of the Pohang Light Source (PLS). The technique used for the study was the phase contrast images were compared with the optical microscopic images of corresponding histological slides. Radiographic images of various diseased tissues showed clear histological details of organelles in normal tissues. Most of cancerous lesions were well differentiated from adjacent normal tissues and detailed histological features of each tumor were clearly identified. Also normal microstructures were identifiable by the phase contrast imaging. Tissue in cancer or other disease showed clearly different findings from those of surrounding normal tissue. For the first time we successfully demonstrated that synchrotron hard X-rays can be used for radiological imaging of relatively thick tissue samples with great histological details.

On-chip clearing of arrays of 3-D cell cultures and micro-tissues.

PubMed

Grist, S M; Nasseri, S S; Poon, T; Roskelley, C; Cheung, K C

2016-07-01

Three-dimensional (3-D) cell cultures are beneficial models for mimicking the complexities of in vivo tissues, especially in tumour studies where transport limitations can complicate response to cancer drugs. 3-D optical microscopy techniques are less involved than traditional embedding and sectioning, but are impeded by optical scattering properties of the tissues. Confocal and even two-photon microscopy limit sample imaging to approximately 100-200 μm depth, which is insufficient to image hypoxic spheroid cores. Optical clearing methods have permitted high-depth imaging of tissues without physical sectioning, but they are difficult to implement for smaller 3-D cultures due to sample loss in solution exchange. In this work, we demonstrate a microfluidic platform for high-throughput on-chip optical clearing of breast cancer spheroids using the SeeDB, Clear(T2), and ScaleSQ clearing methods. Although all three methods are able to effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively clear the sample than Clear(T2); however, SeeDB induces green autofluorescence while ScaleS causes sample expansion. Our unique on-chip implementation permits clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures throughout the process, enabling visualization of the clearing endpoint as well as monitoring of transient changes that could induce image artefacts. Our microfluidic device is compatible with on-chip 3-D cell culture, permitting the use of on-chip clearing at the endpoint after monitoring the same spheroids during their culture. This on-chip method has the potential to improve readout from 3-D cultures, facilitating their use in cell-based assays for high-content drug screening and other applications.

Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing

PubMed Central

Berke, Ian M.; Miola, Joseph P.; David, Michael A.; Smith, Melanie K.; Price, Christopher

2016-01-01

In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues. PMID:26930293

Seeing through Musculoskeletal Tissues: Improving In Situ Imaging of Bone and the Lacunar Canalicular System through Optical Clearing.

PubMed

Berke, Ian M; Miola, Joseph P; David, Michael A; Smith, Melanie K; Price, Christopher

2016-01-01

In situ, cells of the musculoskeletal system reside within complex and often interconnected 3-D environments. Key to better understanding how 3-D tissue and cellular environments regulate musculoskeletal physiology, homeostasis, and health is the use of robust methodologies for directly visualizing cell-cell and cell-matrix architecture in situ. However, the use of standard optical imaging techniques is often of limited utility in deep imaging of intact musculoskeletal tissues due to the highly scattering nature of biological tissues. Drawing inspiration from recent developments in the deep-tissue imaging field, we describe the application of immersion based optical clearing techniques, which utilize the principle of refractive index (RI) matching between the clearing/mounting media and tissue under observation, to improve the deep, in situ imaging of musculoskeletal tissues. To date, few optical clearing techniques have been applied specifically to musculoskeletal tissues, and a systematic comparison of the clearing ability of optical clearing agents in musculoskeletal tissues has yet to be fully demonstrated. In this study we tested the ability of eight different aqueous and non-aqueous clearing agents, with RIs ranging from 1.45 to 1.56, to optically clear murine knee joints and cortical bone. We demonstrated and quantified the ability of these optical clearing agents to clear musculoskeletal tissues and improve both macro- and micro-scale imaging of musculoskeletal tissue across several imaging modalities (stereomicroscopy, spectroscopy, and one-, and two-photon confocal microscopy) and investigational techniques (dynamic bone labeling and en bloc tissue staining). Based upon these findings we believe that optical clearing, in combination with advanced imaging techniques, has the potential to complement classical musculoskeletal analysis techniques; opening the door for improved in situ investigation and quantification of musculoskeletal tissues.

Cell structure and function in the visual cortex of the cat

PubMed Central

Kelly, J. P.; Van Essen, D. C.

1974-01-01

1. The organization of the visual cortex was studied with a technique that allows one to determine the physiology and morphology of individual cells. Micro-electrodes filled with the fluorescent dye Procion yellow were used to record intracellularly from cells in area 17 of the cat. The visual receptive field of each neurone was classified as simple, complex, or hypercomplex, and the cell was then stained by the iontophoretic injection of dye. 2. Fifty neurones were successfully examined in this way, and their structural features were compared to the varieties of cell types seen in Golgi preparations of area 17. The majority of simple units were stellate cells, whereas the majority of complex and hypercomplex units were pyramidal cells. Several neurones belonged to less common morphological types, such as double bouquet cells. Simple cells were concentrated in layer IV, hypercomplex cells in layer II + III, and complex cells in layers II + III, V and VI. 3. Electrically inexcitable cells that had high resting potentials but no impulse activity were stained and identified as glial cells. Glial cells responded to visual stimuli with slow graded depolarizations, and many of them showed a preference for a stimulus orientation similar to the optimal orientation for adjacent neurones. 4. The results show that there is a clear, but not absolute correlation between the major structural and functional classes of cells in the visual cortex. This approach, linking the physiological properties of a single cell to a given morphological type, will help in furthering our understanding of the cerebral cortex. ImagesPlate 4Plate 1Plate 2Plate 3 PMID:4136579

2010 Survey on cell phone use while performing cardiopulmonary bypass.

PubMed

Smith, T; Darling, E; Searles, B

2011-09-01

Cell phone use in the U.S. has increased dramatically over the past decade and text messaging among adults is now mainstream. In professions such as perfusion, where clinical vigilance is essential to patient care, the potential distraction of cell phones may be especially problematic. However, the extent of this as an issue is currently unknown. Therefore, the purpose of this study was to (1) determine the frequency of cell phone use in the perfusion community, and (2) to identify concerns and opinions among perfusionists regarding cell phone use. In October 2010, a link to a 19-question survey (surveymonkey.com) was posted on the AmSECT (PerfList) and Perfusion.com (PerfMail) forums. There were 439 respondents. Demographic distribution is as follows; Chief Perfusionist (30.5%), Staff Perfusionist (62.0%), and Other (7.5%), with age ranges of 20-30 years (14.2%), 30-40 years (26.5%), 40-50 years (26.7%), 50-60 years (26.7%), >60 years (5.9%). The use of a cell phone during the performance of cardiopulmonary bypass (CPB) was reported by 55.6% of perfusionists. Sending text messages while performing CPB was acknowledged by 49.2%, with clear generational differences detected when cross-referenced with age groups. For smart phone features, perfusionists report having accessed e-mail (21%), used the internet (15.1%), or have checked/posted on social networking sites (3.1%) while performing CPB. Safety concerns were expressed by 78.3% who believe that cell phones can introduce a potentially significant safety risk to patients. Speaking on a cell phone and text messaging during CPB are regarded as "always an unsafe practice" by 42.3% and 51.7% of respondents, respectively. Personal distraction by cell phone use that negatively affected performance was admitted by 7.3%, whereas witnessing another perfusionist distracted with phone/text while on CPB was acknowledged by 33.7% of respondents. This survey suggests that the majority of perfusionists believe cell phones raise significant safety issues while operating the heart-lung machine. However, the majority also have used a cell phone while performing this activity. There are clear generational differences in opinions on the role and/or appropriateness of cell phones during bypass. There is a need to further study this issue and, perhaps, to establish consensus on the use of various communication modes within the perfusion community.

Verticillium Infection Triggers VASCULAR-RELATED NAC DOMAIN7–Dependent de Novo Xylem Formation and Enhances Drought Tolerance in Arabidopsis[W

PubMed Central

Reusche, Michael; Thole, Karin; Janz, Dennis; Truskina, Jekaterina; Rindfleisch, Sören; Drübert, Christine; Polle, Andrea; Lipka, Volker; Teichmann, Thomas

2012-01-01

The soilborne fungal plant pathogen Verticillium longisporum invades the roots of its Brassicaceae hosts and proliferates in the plant vascular system. Typical aboveground symptoms of Verticillium infection on Brassica napus and Arabidopsis thaliana are stunted growth, vein clearing, and leaf chloroses. Here, we provide evidence that vein clearing is caused by pathogen-induced transdifferentiation of chloroplast-containing bundle sheath cells to functional xylem elements. In addition, our findings suggest that reinitiation of cambial activity and transdifferentiation of xylem parenchyma cells results in xylem hyperplasia within the vasculature of Arabidopsis leaves, hypocotyls, and roots. The observed de novo xylem formation correlates with Verticillium-induced expression of the VASCULAR-RELATED NAC DOMAIN (VND) transcription factor gene VND7. Transgenic Arabidopsis plants expressing the chimeric repressor VND7-SRDX under control of a Verticillium infection-responsive promoter exhibit reduced de novo xylem formation. Interestingly, infected Arabidopsis wild-type plants show higher drought stress tolerance compared with noninfected plants, whereas this effect is attenuated by suppression of VND7 activity. Together, our results suggest that V. longisporum triggers a tissue-specific developmental plant program that compensates for compromised water transport and enhances the water storage capacity of infected Brassicaceae host plants. In conclusion, we provide evidence that this natural plant–fungus pathosystem has conditionally mutualistic features. PMID:23023171

An unusual cause of hypercalcemic crisis: Water-clear cell double parathyroid adenoma.

PubMed

Yazar, Fatih Mehmet; Karaağaç, Mustafa; İşler, Ali; Bülbüloğlu, Ertan; Ezberci, Fikret

2017-01-01

To evaluate the clinical characteristics of a patient operated for water-clear cell adenoma and to discuss these in the light of relevant literature. PubMed and Google Scholar were searched to identify articles related to water-clear cell adenoma using the following keywords: parathyroid tissue, parathyroid gland, parathyroid cells, parathyroid adenoma, parathyroid hyperplasia, water-clear-cell, and water clear cell. The search included case reports, review articles, and original articles that had been published between January 1990 and November 2014 without any restrictions on language. All articles that contained information on the study population and treatment related data were identified and retrieved. In addition, an evaluation was of a case of a 47-year-old male patient with PHC who was treated at our clinic was conducted. A total of 19 patients, including our new case, (age range: 18 to 81 years, mean±SD: 57.47±16.31 years) were included in the analysis. Eleven patients were female. Information about adenoma location was available from studies involving 17 patients and they indicated the following distribution of locations: left inferior (n=10), right superior (n=4). When preoperative imaging methods were examined, a false negative result was given by ultrasonography in 28.5% of patients and only 57.1% were positive on scintigraphy. Concomitant thyroid papillary carcinoma was determined in 1 patient. The mean tissue dimensions were 3.47±1.73 cm (range, 0.8-6.8 cm). Water-clear cell adenoma, which shows similar clinical characteristics to other parathyroid adenomas, is an uncommon cause of hyperparathyroidism.

Dissuasive exit signage for building fire evacuation.

PubMed

Olander, Joakim; Ronchi, Enrico; Lovreglio, Ruggiero; Nilsson, Daniel

2017-03-01

This work presents the result of a questionnaire study which investigates the design of dissuasive emergency signage, i.e. signage conveying a message of not utilizing a specific exit door. The work analyses and tests a set of key features of dissuasive emergency signage using the Theory of Affordances. The variables having the largest impact on observer preference, interpretation and noticeability of the signage have been identified. Results show that features which clearly negate the exit-message of the original positive exit signage are most effective, for instance a red X-marking placed across the entirety of the exit signage conveys a clear dissuasive message. Other features of note are red flashing lights and alternation of colour. The sense of urgency conveyed by the sign is largely affected by sensory inputs such as red flashing lights or other features which cause the signs to break the tendencies of normalcy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ultrastructural effects of silicone oil on the clear crystalline lens of the human eye.

PubMed

Soliman, Wael; Sharaf, Mohamed; Abdelazeem, Khaled; El-Gamal, Dalia; Nafady, Allam

2018-03-01

To evaluate light and electron microscopic changes of the anterior capsule and its epithelium after clear lens extraction of vitrectomized myopic eyes with silicone oil tamponade. This prospective, controlled, non-randomized, interventional study included 20 anterior lens capsular specimens that were excised during combined clear lens extraction and silicone oil removal from previously vitrectomized highly myopic patients with silicone oil tamponade for previous retinal detachment surgeries. The specimens were examined via light microscopy and electron microscopy and compared with 20 anterior capsule specimens removed during clear lens extraction of non-vitrectomized highly myopic eyes. Light microscopic examination of clear lens anterior capsule specimens of vitrectomized myopic eyes filled with silicone oil showed relatively more flat cells with irregular outline of lens' epithelial cells with wide intercellular spaces, deeply stained nuclei, and multiple intracytoplasmic vacuoles. Scanning electron microscopy revealed collagenous surfaces filled with multiple pits, depressions, and abnormal deposits. Transmission electron microscopy revealed lens epithelial cells with apoptotic changes, many cytoplasmic vacuoles, and filopodia-like protrusions between lens epithelial cells and the capsule. Epithelial proliferation and multilayering were also observed. silicone oil may play a role in the development of apoptotic and histopathological changes in clear lens epithelial cells. Clarity of the lens at the time of silicone oil removal does not indicate an absence of cataractous changes. We found justification of combined clear lens extraction and silicone oil removal or combined phacovitrectomy when silicone oil injection is planned, but further long-term studies with larger patient groups are required.

Structural development of wheat nutrient transfer tissues and their relationships with filial tissues development.

PubMed

Xurun, Yu; Xinyu, Chen; Liang, Zhou; Jing, Zhang; Heng, Yu; Shanshan, Shao; Fei, Xiong; Zhong, Wang

2015-03-01

Nutrients from spikelet phloem are commonly delivered to endosperm via caryopsis nutrient transfer tissues (NTTs). Elucidation of NTTs development is paramount to developing an understanding of the control of assimilate partitioning. Little information was available on the structural development of the entire NTTs and their functions, particularly those involved in the relationship between development of NTTs and growth of filial tissues including endosperm and embryo. In this study, wheat caryopses at different development stages were collected for observation of the NTTs by light microscopy, stereoscopic microscopy, and scanning electron microscopy. The cytological features of NTTs in the developing wheat caryopsis were clearly elucidated. The results were as follows: NTTs in the wheat caryopsis include maternal transfer tissues that are composed of vascular bundle, chalaza and nucellar projection transfer cells, and endosperm transfer tissues that consist of the aleurone transfer cells, starchy endosperm transfer cells, and endosperm conducting cells. The initiation, development, and apoptosis of these NTTs revealed the pattern of temporal and spatial gradient and were closely coordinated with endosperm and embryo development. These results may give us a further understanding about the functions of NTTs and their relationships with endosperm and embryo development.

Adenomyoepithelioma of the breast with associated atypical lobular hyperplasia: a previously unrecognized association with management implications.

PubMed

Zhang, Shuang; Huo, Lei; Arribas, Elsa; Middleton, Lavinia P

2015-02-01

Adenomyoepitheliomas of breast are rare tumors. We report for the first time a case of an adenomyoepithelioma of the breast with associated lobular neoplasia. A 53-year-old woman had an annual screening mammogram, which identified areas of asymmetry in her left breast at 4-5-o'clock position. Resection of the masses revealed a well-circumscribed, gray-white, firm discrete nodule (0.8 × 0.4 × 0.3 cm). The tumor was composed of both adenomyoepithelial cell hyperplasia and focal atypical lobular hyperplasia. The 2 cell populations had some overlapping histologic features. Immunohistochemical analysis demonstrated a biphasic proliferation with approximately equal parts of luminal epithelial cells with clear and rounded appearance and myoepithelial cells. The myoepithelial component of the proliferation expressed myosin, p63, CK5/6, S-100, and dimly expressed E-cadherin. The epithelial component of the proliferation strongly expressed E-cadherin. In the areas of atypical lobular hyperplasia, there was distinct loss E-cadherin expression. Awareness of this association is highly important to provide these patients adequate follow-up and treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Surface morphology of taste buds in catfish barbels.

PubMed

Ovalle, W K; Shinn, S L

1977-03-16

External taste buds abound on barbels of the adult catfish Corydoras arcuatus. When examined by scanning electron microscopy, they are visualized as a series of punctate, conical elevations projecting from the general surface epithelium. All taste buds were found to be of one type. Both their external and internal surface features could be clearly elucidated on intact barbels and in barbels fractured transversely at various positions along their length. An extensive nerve terminal network penetrates the base of each taste bud. Two populations of elongated cells bearing prominent microvilli project through the central pore at the tip of each bud. One set of microvilli is thicker, longer and more club-shaped than its counterpart. While both are randomly distributed within each central pore, the small, short microvilli appear to outnumber the larger ones. A third population of cells, devoid of any apical microvilli, was also seen in some of the taste buds examined internally. These cells do not project to the external surface and are interpreted as "basal" cells described in previous light and transmission electron microscope studies of taste buds in other vertebrate species. The functional significance of some of these morphological findings is discussed.

The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy.

PubMed

Anichini, Andrea; Tassi, Elena; Grazia, Giulia; Mortarini, Roberta

2018-06-01

Immunotherapy of non-small cell lung cancer (NSCLC), by immune checkpoint inhibitors, has profoundly improved the clinical management of advanced disease. However, only a fraction of patients respond and no effective predictive factors have been defined. Here, we discuss the prospects for identification of such predictors of response to immunotherapy, by fostering an in-depth analysis of the immune landscape of NSCLC. The emerging picture, from several recent studies, is that the immune contexture of NSCLC lesions is a complex and heterogeneous feature, as documented by analysis for frequency, phenotype and spatial distribution of innate and adaptive immune cells, and by characterization of functional status of inhibitory receptor + T cells. The complexity of the immune landscape of NSCLC stems from the interaction of several factors, including tumor histology, molecular subtype, main oncogenic drivers, nonsynonymous mutational load, tumor aneuploidy, clonal heterogeneity and tumor evolution, as well as the process of epithelial-mesenchymal transition. All these factors contribute to shape NSCLC immune profiles that have clear prognostic significance. An integrated analysis of the immune and molecular profile of the neoplastic lesions may allow to define the potential predictive role of the immune landscape for response to immunotherapy.

PH-sensitive fluorescence detection by diffuse fluorescence tomography

NASA Astrophysics Data System (ADS)

Li, Jiao; Gao, Feng; Duan, Linjing; Wang, Xin; Zhang, Limin; Zhao, Huijuan

2012-03-01

The importance of cellular pH has been shown clearly in the study of cell activity, pathological feature, drug metabolism, etc. Monitoring pH changes of living cells and imaging the regions with abnormal pH values in vivo could provide the physiologic and pathologic information for the research of the cell biology, pharmacokinetics, diagnostics and therapeutics of certain diseases such as cancer. Thus, pH-sensitive fluorescence imaging of bulk tissues has been attracting great attention in the regime of near-infrared diffuse fluorescence tomography (DFT), an efficient small-animal imaging tool. In this paper, the feasibility of quantifying pH-sensitive fluorescence targets in turbid medium is investigated using both time-domain and steady-state DFT methods. By use of the specifically designed time-domain and continuous-wave systems and the previously proposed image reconstruction scheme, we validate the method through 2-dimensional imaging experiments on a small-animal-sized phantom with multiply targets of distinct pH values. The results show that the approach can localize the targets with reasonable accuracy and achieve quantitative reconstruction of the pH-sensitive fluorescent yield.

Adipose Tissue as a Strategic Source of Mesenchymal Stem Cells in Bone Regeneration: A Topical Review on the Most Promising Craniomaxillofacial Applications

PubMed Central

Marrelli, Massimo; Amantea, Massimiliano; Rengo, Carlo; Rengo, Sandro; Goldberg, Michel; Spagnuolo, Gianrico

2017-01-01

Bone regeneration in craniomaxillofacial surgery represents an issue that involves both surgical and aesthetic aspects. The most recent studies on bone tissue engineering involving adipose-derived stromal/stem cells (ASCs) have clearly demonstrated that such cells can play a crucial role in the treatment of craniomaxillofacial defects, given their strong commitment towards the osteogenic phenotype. A deeper knowledge of the molecular mechanisms underlying ASCs is crucial for a correct understanding of the potentialities of ASCs-based therapies in the most complex maxillofacial applications. In this topical review, we analyzed the molecular mechanisms of ASCs related to their support toward angiogenesis and osteogenesis, during bone regeneration. Moreover, we analyzed both case reports and clinical trials reporting the most promising clinical applications of ASCs in the treatment of craniomaxillofacial defects. Our study aimed to report the main molecular and clinical features shown by ASCs, used as a therapeutic support in bone engineering, as compared to the use of conventional autologous and allogeneic bone grafts. PMID:29027958

Higher cell stiffness indicating lower metastatic potential in B16 melanoma cell variants and in (-)-epigallocatechin gallate-treated cells.

PubMed

Watanabe, Tatsuro; Kuramochi, Hiromi; Takahashi, Atsushi; Imai, Kazue; Katsuta, Naoko; Nakayama, Tomonobu; Fujiki, Hirota; Suganuma, Masami

2012-05-01

To understand how nanomechanical stiffness affects metastatic potential, we studied the relationship between cell migration, a characteristic of metastasis, and cell stiffness using atomic force microscopy (AFM), which can measure stiffness (elasticity) of individual living cells. Migration and cell stiffness of three metastatic B16 melanoma variants (B16-F10, B16-BL6, and B16-F1 cells), and also effects of (-)-epigallocatechin gallate (EGCG), were studied using Transwell assay and AFM. Migration of B16-F10 and B16-BL6 cells was 3 and 2 times higher than that of B16-F1 cells in Transwell assay, and cell stiffness determined by AFM was also different among the three variants, although they have similar morphologies and the same growth rates: Means of Young's modulus were 350.8 ± 4.8 Pa for B16-F10 cells, 661.9 ± 16.5 Pa for B16-BL6 cells, and 727.2 ± 13.0 Pa for B16-F1 cells. AFM measurements revealed that highly motile B16-F10 cells have low cell stiffness, and low motile and metastatic B16-F1 cells have high cell stiffness: Nanomechanical stiffness is inversely correlated with migration potential. Treatment of highly motile B16-F10 cells with EGCG increased cell stiffness 2-fold and inhibited migration of the cells. Our study with AFM clearly demonstrates that cell stiffness is a reliable quantitative indicator of migration potential, and very likely metastatic potential, even in morphologically similar cells. And increased cell stiffness may be a key nanomechanical feature in inhibition of metastasis.

Classification Features of US Images Liver Extracted with Co-occurrence Matrix Using the Nearest Neighbor Algorithm

NASA Astrophysics Data System (ADS)

Moldovanu, Simona; Bibicu, Dorin; Moraru, Luminita; Nicolae, Mariana Carmen

2011-12-01

Co-occurrence matrix has been applied successfully for echographic images characterization because it contains information about spatial distribution of grey-scale levels in an image. The paper deals with the analysis of pixels in selected regions of interest of an US image of the liver. The useful information obtained refers to texture features such as entropy, contrast, dissimilarity and correlation extract with co-occurrence matrix. The analyzed US images were grouped in two distinct sets: healthy liver and steatosis (or fatty) liver. These two sets of echographic images of the liver build a database that includes only histological confirmed cases: 10 images of healthy liver and 10 images of steatosis liver. The healthy subjects help to compute four textural indices and as well as control dataset. We chose to study these diseases because the steatosis is the abnormal retention of lipids in cells. The texture features are statistical measures and they can be used to characterize irregularity of tissues. The goal is to extract the information using the Nearest Neighbor classification algorithm. The K-NN algorithm is a powerful tool to classify features textures by means of grouping in a training set using healthy liver, on the one hand, and in a holdout set using the features textures of steatosis liver, on the other hand. The results could be used to quantify the texture information and will allow a clear detection between health and steatosis liver.

Ferroptosis is Involved in Acetaminophen Induced Cell Death.

PubMed

Lőrincz, Tamás; Jemnitz, Katalin; Kardon, Tamás; Mandl, József; Szarka, András

2015-09-01

The recently described form of programmed cell death, ferroptosis can be induced by agents causing GSH depletion or the inhibition of GPX4. Ferroptosis clearly shows distinct morphologic, biochemical and genetic features from apoptosis, necrosis and autophagy. Since NAPQI the highly reactive metabolite of the widely applied analgesic and antipyretic, acetaminophen induces a cell death which can be characterized by GSH depletion, GPX inhibition and caspase independency the involvement of ferroptosis in acetaminophen induced cell death has been investigated. The specific ferroptosis inhibitor ferrostatin-1 failed to elevate the viability of acetaminophen treated HepG2 cells. It should be noticed that these cells do not form NAPQI due to the lack of phase I enzyme expression therefore GSH depletion cannot be observed. However in the case of acetaminophen treated primary mouse hepatocytes the significant elevation of cell viability could be observed upon ferrostatin-1 treatment. Similar to ferrostatin-1 treatment, the addition of the RIP1 kinase inhibitor necrostatin-1 could also elevate the viability of acetaminophen treated primary hepatocytes. Ferrostatin-1 has no influence on the expression of CYP2E1 or on the cellular GSH level which suggest that the protective effect of ferrostatin-1 in APAP induced cell death is not based on the reduced metabolism of APAP to NAPQI or on altered NAPQI conjugation by cellular GSH. Our results suggest that beyond necroptosis and apoptosis a third programmed cell death, ferroptosis is also involved in acetaminophen induced cell death in primary hepatocytes.

Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer

ClinicalTrials.gov

2017-05-04

Endometrial Clear Cell Adenocarcinoma; Estrogen Receptor Negative; Ovarian Clear Cell Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

High Occurrence of Non-Clear Cell Renal Cell Carcinoma in Oman.

PubMed

Venniyoor, Ajit; Essam, Abdul Monem; Ramadhan, Fatma; Keswani, Heeranand; Mehdi, Itrat; Bahrani, Bassim Al

2016-01-01

It is conventionally accepted that renal cell carcinoma (RCC) occurs in older patients and the clear cell type is the most common histology. However, ethnic variations exist and this study was carried out to determine the epidemiological pattern of RCC in Oman. Ninety RCC patients who presented to a tertiary care center in the Sultanate of Oman from 2010 to 2014 were studied. The main findings were that the median age of presentation was low, more patients presented with localized stage, and there was a higher incidence of non-clear (especially papillary) histology. Data from other Gulf countries and possible reasons for the different profile are discussed.

Clear cell renal cell carcinoma: a comparative study of histological and chromosomal characteristics between primary tumors and their corresponding metastases.

PubMed

Dagher, Julien; Kammerer-Jacquet, Solène-Florence; Dugay, Frédéric; Beaumont, Marion; Lespagnol, Alexandra; Cornevin, Laurence; Verhoest, Grégory; Bensalah, Karim; Rioux-Leclercq, Nathalie; Belaud-Rotureau, Marc-Antoine

2017-07-01

Clear cell renal cell carcinoma (ccRCC) has a poor prognosis with a 50% risk of metastases. Little is known about the phenotypic and molecular profiles of metastases regarding their corresponding primary tumors. This study aimed to screen phenotypic and genotypic differences between metastases and their corresponding primary tumors. We selected four cases with available frozen material. The histological, immunohistochemical (VEGFA, CD31, SMA, Ki67, p53, PAR-3), FISH (VHL gene), next-generation sequencing (VHL and c-MET genes), multiplex ligation-dependent probe amplification, and array-(comparative genomic hybridization) CGH analyses were realized. Metastases were nodal, hepatic (synchronous), adrenal, and pulmonary (metachronous). High-grade tumor cells were significantly more frequent in metastases (p = 0.019). Metastases and high-grade zones of primary tumors shared similar characteristics compared to low-grade zones: a lower microscopic vascular density (43.5 vs 382.5 vessels/mm 2 ; p = 0.0027), a higher expression of VEGF (73 vs 10%, p = 0.045), Ki67 (37.6 vs 8.3%; p = 0.011), and p53 (54 vs 10.6%; p = 0.081), and a cytoplasmic and membranous PAR-3 staining. Metastases exhibited more chromosomal imbalances than primary tumors in total (18.75 ± 6.8; p = 0.044) with more genomic gains (13.5 ± 7; p = 0.013). The loss of chromosome 9 and gain of Xq were found in both primary tumors and metastases but gains of loci or chromosomes 2p, 3q, 5, 8q, 12, and 20 were only found in metastases. The VHL gene status was similar in each tumor couple. Although metastases and primary tumors share common histological features, this study highlights chromosomal differences specific to metastases which could be involved in ccRCC metastatic evolution.

[Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis].

PubMed

Xia, Qiuyuan; Shi, Shanshan; Shen, Qin; Wei, Xue; Wang, Xuan; Ma, Henghui; Lu, Zhenfeng; Zhou, Xiaojun; Rao, Qiu

2015-12-01

To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion. A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature. The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis. TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.

Mutational profiles of Brenner tumors show distinctive features uncoupling urothelial carcinomas and ovarian carcinoma with transitional cell histology.

PubMed

Pfarr, Nicole; Darb-Esfahani, Silvia; Leichsenring, Jonas; Taube, Eliane; Boxberg, Melanie; Braicu, Ioana; Jesinghaus, Moritz; Penzel, Roland; Endris, Volker; Noske, Aurelia; Weichert, Wilko; Schirmacher, Peter; Denkert, Carsten; Stenzinger, Albrecht

2017-10-01

Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in-situ hybridization (FISH) and quantitative PCR-based copy number assays. Additionally, we analyzed the TERT promotor region by conventional Sanger sequencing. We identified 25 different point mutations in 23 of the analyzed genes in BTs and 10 mutations in 8 genes in TCCs. About 57% percent of mutations occurred in genes involved in cell cycle control, DNA repair, and epigenetic regulation processes. All TCC cases harbored TP53 mutations whereas all BTs were negative and none of the mutations observed in BTs were present in TCCs. CNV analysis revealed recurrent MDM2 amplifications in 3 out of 4 of the malignant BT cases with one case harboring a concomitant amplification of CCND1. No mutations were observed in the TERT promoter region in BTs and TCCs, which is mutated in about 50%-75% of urothelial carcinoma and in 16% of ovarian clear-cell carcinomas. In conclusion, our study highlights distinct genetic features of BTs, and detection of the triplet phenotype MDM2 amplification/TP53 wt/TERT wt may aid diagnosis of malignant BT in difficult cases. Moreover, selected genetic lesions may be clinically exploitable in a metastatic setting. © 2017 Wiley Periodicals, Inc.

Advances in Evaluation of Chronic Diarrhea in Infants.

PubMed

Thiagarajah, Jay R; Kamin, Daniel S; Acra, Sari; Goldsmith, Jeffrey D; Roland, Joseph T; Lencer, Wayne I; Muise, Aleixo M; Goldenring, James R; Avitzur, Yaron; Martín, Martín G

2018-06-01

Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

PubMed

Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

2014-01-01

Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.

Malassezia virulence determinants.

PubMed

Hort, Wiebke; Mayser, Peter

2011-04-01

Malassezia yeasts are associated with a number of dermatologic and systemic diseases in humans and animals. Pityriasis versicolor is amongst these diseases and represents one of the most common human skin diseases. Beyond that, the role of Malassezia yeasts in the pathogenesis of other skin diseases such as psoriasis, seborrheic dermatitis and confluent and reticulate papillomatosis is discussed but remains less clear. Clear pathogenetic mechanisms of the above-mentioned diseases are not known so far. The review presents new findings on virulence factors of Malassezia yeasts, shedding light on the pathogenesis of Malassezia-associated diseases. Several virulence factors in Malassezia yeasts are known, based on their enzymatic lipolytic activity resulting in the production of distinct metabolites and special cell wall features. Recently, a secondary metabolic pathway possibly implicated in the pathogenesis of pityriasis versicolor was described. The article presents virulence factors of Malassezia yeasts ranging from irritant metabolic byproducts to highly bioactive indole derivatives and attempts to clarify their pathogenic implications in the different diseases. Special emphasis is given to the pathogenesis of pityriasis versicolor, as it represents the disease wherein the causative relationship with Malassezia yeasts appears the most obvious.

A feature selection approach towards progressive vector transmission over the Internet

NASA Astrophysics Data System (ADS)

Miao, Ru; Song, Jia; Feng, Min

2017-09-01

WebGIS has been applied for visualizing and sharing geospatial information popularly over the Internet. In order to improve the efficiency of the client applications, the web-based progressive vector transmission approach is proposed. Important features should be selected and transferred firstly, and the methods for measuring the importance of features should be further considered in the progressive transmission. However, studies on progressive transmission for large-volume vector data have mostly focused on map generalization in the field of cartography, but rarely discussed on the selection of geographic features quantitatively. This paper applies information theory for measuring the feature importance of vector maps. A measurement model for the amount of information of vector features is defined based upon the amount of information for dealing with feature selection issues. The measurement model involves geometry factor, spatial distribution factor and thematic attribute factor. Moreover, a real-time transport protocol (RTP)-based progressive transmission method is then presented to improve the transmission of vector data. To clearly demonstrate the essential methodology and key techniques, a prototype for web-based progressive vector transmission is presented, and an experiment of progressive selection and transmission for vector features is conducted. The experimental results indicate that our approach clearly improves the performance and end-user experience of delivering and manipulating large vector data over the Internet.

A comparative study of machine learning methods for time-to-event survival data for radiomics risk modelling.

PubMed

Leger, Stefan; Zwanenburg, Alex; Pilz, Karoline; Lohaus, Fabian; Linge, Annett; Zöphel, Klaus; Kotzerke, Jörg; Schreiber, Andreas; Tinhofer, Inge; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Troost, Esther G C; Löck, Steffen; Richter, Christian

2017-10-16

Radiomics applies machine learning algorithms to quantitative imaging data to characterise the tumour phenotype and predict clinical outcome. For the development of radiomics risk models, a variety of different algorithms is available and it is not clear which one gives optimal results. Therefore, we assessed the performance of 11 machine learning algorithms combined with 12 feature selection methods by the concordance index (C-Index), to predict loco-regional tumour control (LRC) and overall survival for patients with head and neck squamous cell carcinoma. The considered algorithms are able to deal with continuous time-to-event survival data. Feature selection and model building were performed on a multicentre cohort (213 patients) and validated using an independent cohort (80 patients). We found several combinations of machine learning algorithms and feature selection methods which achieve similar results, e.g. C-Index = 0.71 and BT-COX: C-Index = 0.70 in combination with Spearman feature selection. Using the best performing models, patients were stratified into groups of low and high risk of recurrence. Significant differences in LRC were obtained between both groups on the validation cohort. Based on the presented analysis, we identified a subset of algorithms which should be considered in future radiomics studies to develop stable and clinically relevant predictive models for time-to-event endpoints.

Expression of EphA2 protein is positively associated with age, tumor size and Fuhrman nuclear grade in clear cell renal cell carcinomas.

PubMed

Wang, Longxin; Hu, Haibing; Tian, Feng; Zhou, Wenquan; Zhou, Shuigen; Wang, Jiandong

2015-01-01

The receptor tyrosine kinase of EphA2 has been shown frequently overexpressed in various types of human carcinomas, which implicated that it plays important roles in carcinogenesis. Although EphA2 protein expression has been investigated in many types of human carcinomas, the relationship between the expression of EphA2 protein in clear cell renal cell carcinoma was not well documented. In the present study, using specific anit-EphA2 polyclonal antibody and immunohistochemistry, we evaluated EphA2 protein expression levels in clear cell RCC specimens surgically resected from 90 patients. Our results shows that EphA2 protein was positively expressed in all normal renal tubes of 90 samples (100%, 3+), which was expressed at low levels in renal cortex but high levels in the collecting ducts of the renal medulla and papilla. EphA2 was negatively or weakly expressed in 30 out of 90 samples (33.3%, 0/1+), moderately expressed in 24 samples (26.7%, 2+) and strongly expressed in 36 samples (40%, 3+). Expression of EphA2 was positively associated with age (P=0.029), tumor diameters (P<0.001) and Fuhrman nuclear grade (P<0.001). Our results indicate that EphA2 variably expressed in clear cell renal cell carcinomas. High expression of EphA2 was more often found in big size and high nuclear grade tumors, which indicated EphA2 protein may be used as a new marker for the prognosis of clear cell renal cell carcinoma.

Rhabdoid and Undifferentiated Phenotype in Renal Cell Carcinoma: Analysis of 32 Cases Indicating a Distinctive Common Pathway of Dedifferentiation Frequently Associated With SWI/SNF Complex Deficiency.

PubMed

Agaimy, Abbas; Cheng, Liang; Egevad, Lars; Feyerabend, Bernd; Hes, Ondřej; Keck, Bastian; Pizzolitto, Stefano; Sioletic, Stefano; Wullich, Bernd; Hartmann, Arndt

2017-02-01

Undifferentiated (anaplastic) and rhabdoid cell features are increasingly recognized as adverse prognostic findings in renal cell carcinoma (RCC), but their molecular pathogenesis has not been studied sufficiently. Recent studies identified alterations in the Switch Sucrose nonfermentable (SWI/SNF) chromatin remodeling complex as molecular mechanisms underlying dedifferentiation and rhabdoid features in carcinomas of different organs. We herein have analyzed 32 undifferentiated RCCs having in common an undifferentiated (anaplastic) phenotype, prominent rhabdoid features, or both, irrespective of the presence or absence of conventional RCC component. Cases were stained with 6 SWI/SNF pathway members (SMARCB1, SMARCA2, SMARCA4, ARID1A, SMARCC1, and SMARCC2) in addition to conventional RCC markers. Patients were 20 males and 12 females aged 32 to 85 years (mean, 59). A total of 22/27 patients with known stage presented with ≥pT3. A differentiated component varying from microscopic to major component was detected in 20/32 cases (16 clear cell and 2 cases each chromophobe and papillary RCC). The undifferentiated component varied from rhabdoid dyscohesive cells to large epithelioid to small monotonous anaplastic cells. Variable loss of at least 1 SWI/SNF complex subunit was noted in the undifferentiated/rhabdoid component of 21/32 cases (65%) compared with intact or reduced expression in the differentiated component. A total of 15/17 patients (88%) with follow-up died of metastatic disease (mostly within 1 y). Only 2 patients were disease free at last follow-up (1 and 6 y). No difference in survival, age distribution, or sex was observed between the SWI/SNF-deficient and the SWI/SNF-intact group. This is the first study exploring the role of SWI/SNF deficiency as a potential mechanism underlying undifferentiated and rhabdoid phenotype in RCC. Our results highlight the association between the aggressive rhabdoid phenotype and the SWI/SNF complex deficiency, consistent with studies on similar neoplasms in other organs. Thorough sampling of such tumors that are usually huge and locally advanced is necessary for recognizing the clone of origin and hence for proper subtyping and also for differentiating them from undifferentiated urothelial carcinoma.

Expression of CD105 cancer stem cell marker in three subtypes of renal cell carcinoma.

PubMed

Saeednejad Zanjani, Leili; Madjd, Zahra; Abolhasani, Maryam; Shariftabrizi, Ahmad; Rasti, Arezoo; Asgari, Mojgan

2018-01-01

CD105 is recently described as a cancer stem cell (CSC) marker. The present study was aimed to investigate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of renal cell carcinoma (RCC). Expression of CD105 was evaluated using immunohistochemistry in RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), papillary, and chromophobe RCCs. The association between CD105 expression and clinicopathological features as well as survival outcomes was determined. In ccRCC, increased tumoral cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, renal vein invasion, and microvascular invasion (MVI). In addition, MVI was associated with a worse overall survival (OS). Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS both in case of tumoral cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. We showed that CD105 expression was associated with more aggressive tumor behavior, more advanced disease, and worse prognosis in ccRCC but not in the other RCC subtypes.

CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells

PubMed Central

Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

2012-01-01

Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms involved in its regulation are still unknown. Using human neuroblastoma cells as a model system we found that an increase in CDKL5 expression caused an arrest of the cell cycle in the G0/G1 phases and induced cellular differentiation. Interestingly, CDKL5 expression was inhibited by MYCN, a transcription factor that promotes cell proliferation during brain development and plays a relevant role in neuroblastoma biology. Through a combination of different and complementary molecular and cellular approaches we could show that MYCN acts as a direct repressor of the CDKL5 promoter. Overall our findings unveil a functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation. The fact that CDKL5 is involved in the control of both neuron proliferation and differentiation may help understand the early appearance of neurological symptoms in patients with mutations in CDKL5. PMID:22921766

An Xp11.2 translocation renal cell carcinoma with SMARCB1 (INI1) inactivation in adult end-stage renal disease: a case report.

PubMed

Yu, Lu; Li, Jun; Xu, Sanpeng; Navia Miranda, Mariajose; Wang, Guoping; Duan, Yaqi

2016-10-12

Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data. Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity. In some areas, non-adhesive tumor cells with eccentric nuclei were observed. Immunohistochemically (IHC), the tumor cells are positive for TFE3 and the renal tubular markers (PAX2 and PAX8), and completely negative for SMARCB1, an oncosuppressor protein. Break-apart florescence in situ hybridization and reverse transcription polymerase chain reaction confirmed TFE3 rearrangement on Xp11.2 and the presence of ASPSCR1-TFE3 fusion gene. DNA sequencing revealed a frameshift mutation in exon 4 of SMARCB1 gene. It is important to recognize this rare RCC with both TFE3 rearrangement and SMARCB1 inactivation, as the prognosis and therapeutic strategies, particularly targeted therapies for such tumors, might be different.

Analysis of synovial fluid of the Capybara's stifle joints.

PubMed

Brombini, Giovanna C; Rahal, Sheila C; Bergamini, Bruno C S; Lopes, Raimundo S; Santos, Ivan F C; Schimming, Bruno C

2017-03-01

Although normal synovial fluid has been well characterized in domestic animals such as dogs, cats, horses, and cows, the available information on larger rodents is scarce. The purpose of the study was to analyze the physical, chemical, and cytologic characteristics of the synovial fluid in stifle joints of Capybaras. Five free-ranging adult female Capybaras (Hydrochoerus hydrochaeris), weighing from 37 to 56 kg were used. Synovial fluid was obtained by aspiration of 10 stifle joints. Samples were analyzed for physical, chemical, and cytologic properties. Spontaneous clotting was negative in 9 samples. Most synovial fluids had pH 8, and protein concentrations ranged from 1.6 to 3.6 g/dL. The mucin clot test was good in all 6 samples that were tested. Nucleated cell counts ranged from 140 to 508 cells/μL. Relative differential leukocyte counts demonstrated a predominance of mononuclear cells (97.6%), including 76.2% undifferentiated mononuclear cells, 18.1% macrophages, and 3.66% lymphocytes. Polymorphonuclear cells included 1.83% neutrophils and 0.2% eosinophils. The synovial stifle joint fluid of healthy free-ranging adult Capybaras is clear, colorless, viscous, and with chemical features and cytologic findings similar to those seen in domestic animals. © 2017 American Society for Veterinary Clinical Pathology.

Melanotic Translocation Renal Cell Carcinoma With a Novel ARID1B-TFE3 Gene Fusion.

PubMed

Antic, Tatjana; Taxy, Jerome B; Alikhan, Mir; Segal, Jeremy

2017-11-01

A 36-year-old male was found to have a 7.0 cm left upper pole renal mass on renal ultrasound. Following nephrectomy, the mass was grossly ill-demarcated, friable and red-brown, invading renal parenchyma, hilar fat and the renal vein. Microscopically, the tumor had a nested and papillary architecture. The cells demonstrated abundant clear and eosinophilic cytoplasm and focal intracytoplasmic melanin pigment. Nucleoli were prominent. By immunohistochemistry, the tumor was positive for TFE3; HMB-45 stained approximately 5% of tumor cells corresponding to the histologic melanin pigment, which was confirmed with Fontana-Masson stain with bleach. Immunostains for PAX8, CD10, MiTF, and CAIX were negative; keratins Cam 5.2 and AE1/AE3 were focally positive. Targeted next-generation sequencing revealed an ARID1B-TFE3 gene fusion. Melanotic Xp11 renal cell carcinoma is a rare, pigment containing translocation variant demonstrating overlapping features with melanoma and is usually associated with an SFPQ-TFE3 gene fusion. The patient is alive and without evidence of disease 7 years after his diagnosis. The combination of high grade histopathology, the presence of melanin, absent PAX8, keratin positivity, and relatively indolent clinical behavior with a unique translocation may warrant recognition as a distinct renal cell carcinoma translocation subtype.

Molecular pathogenesis of ovarian clear cell carcinoma.

PubMed

Gounaris, Ioannis; Brenton, James D

2015-01-01

Ovarian clear cell carcinoma is a distinct subtype of epithelial ovarian cancer, characterized by an association with endometriosis, glycogen accumulation and resistance to chemotherapy. Key driver events, including ARID1A mutations and HNF1B overexpression, have been recently identified and their functional characterization is ongoing. Additionally, the role of glycogen in promoting the malignant phenotype is coming under scrutiny. Appreciation of the notion that ovarian clear cell carcinoma is essentially an ectopic uterine cancer will hopefully lead to improved animal models of the disease, in turn paving the way for effective treatments.

Systemic therapy for metastatic renal cell carcinoma in treatment naïve patients: a risk-based approach.

PubMed

Bukowski, Ronald M

2010-10-01

Kidney cancer is the ninth most common cancer in the USA, with an annual incidence of approximately 55,000 cases per year. Over 13,000 patients are estimated to die from this disease annually. Cloning of the VHL gene, recognition of the associated abnormalities in sporadic clear-cell carcinoma, and its role as a regulator of the hypoxic response, were important milestones in our understanding of renal-cell carcinoma (RCC) biology and the recognition of the vascular endothelial growth factor (VEGF) dependency of RCC. A variety of clinical features, including histologic features, prognostic factors, and patient history of comorbid illness, provide the framework in which the results of recent clinical trials and regulatory approvals of these agents are utilized to develop treatment recommendations for the largest metastatic patient RCC group, the therapy naïve individual. The rationale for use of VEGF-targeted therapy in advanced RCC patients and the recently developed treatment options for these individuals are reviewed. Regulatory approval of sorafenib for the treatment of metastatic RCC (mRCC), was followed by the approval of sunitinib, temsirolimus, bevacizumab plus interferon (IFNα), everolimus, and--most recently--pazopanib. These licences were granted from late 2005 through late 2009, a very short span of 4 years. In treatment-naïve mRCC patients, sunitinib, sorafenib, pazopanib, bevacizumab + IFNα, and temsirolimus were approved by the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMEA). The clinical trials and data supporting these approvals are reviewed. This review examines these developments and provides the reader an overview and understanding of available current systemic therapy options for treatment-naïve mRCC patients. As multiple treatment options are now available for treatment-naïve mRCC patients, an understanding of how to utilize this group of agents is required. The use of various clinical features allows a rational approach to therapy selection. These features include prior treatment status, histologic subtype, and prognostic group. Further refinement of therapy selection is required and will require further biologic information as well as comparative randomized trials.

Selfish cells in altruistic cell society - a theoretical oncology.

PubMed

Chigira, M

1993-09-01

In multicellular organisms, internal evolution of individual cells is strictly forbidden and 'evolutional' DNA replication should be performed only by the sexual reproduction system. Wholistic negative control system called 'homeostasis' serves all service to germ line cells. All somatic cells are altruistic to the germ line cells. However, in malignant tumors, it seems that individual cells replicate and behave 'selfishly' and evolve against the internal microenvironment. Tumor cells only express the occult selfishness which is programmed in normal cells a priori. This phenomenon is based on the failure of identical DNA replication, and results in 'autonomy' and 'anomie' of cellular society as shown in tumor cells. Genetic programs of normal cells connote this cellular autonomy and anomie introduced by the deletion of regulators on structure genes. It is rather paradoxical that the somatic cells get their freedom from wholistic negative regulation programmed internally. However, this is not a true paradox, since multicellular organisms have clearly been evolved from 'monads' in which cells proliferate without wholistic regulation. Somatic cells revolt against germ cell DNA, called 'selfish replicator' by Dawkins. It is an inevitable destiny that the 'selfishness' coded in genome should be revenged by itself. Selfish replicator in germ cell line should be revolted by its selfishness in the expansion of somatic cells, since they have an orthogenesis to get more selfishness in order to increase their genome. Tumor heterogeneity and progression can be fully explained by this self-contradictory process which produces heterogeneous gene copies different from the original clone in the tumor, although 'selfish' gene replication is the final target of being. Furthermore, we have to discard the concept of clonality of tumor cells since genetic instability is a fundamental feature of tumors. Finally, tumor cells and proto-oncogenes can be considered as the ultimate parasite to germ line cells.

Optical cell monitoring system for underwater targets

NASA Astrophysics Data System (ADS)

Moon, SangJun; Manzur, Fahim; Manzur, Tariq; Demirci, Utkan

2008-10-01

We demonstrate a cell based detection system that could be used for monitoring an underwater target volume and environment using a microfluidic chip and charge-coupled-device (CCD). This technique allows us to capture specific cells and enumerate these cells on a large area on a microchip. The microfluidic chip and a lens-less imaging platform were then merged to monitor cell populations and morphologies as a system that may find use in distributed sensor networks. The chip, featuring surface chemistry and automatic cell imaging, was fabricated from a cover glass slide, double sided adhesive film and a transparent Polymethlymetacrylate (PMMA) slab. The optically clear chip allows detecting cells with a CCD sensor. These chips were fabricated with a laser cutter without the use of photolithography. We utilized CD4+ cells that are captured on the floor of a microfluidic chip due to the ability to address specific target cells using antibody-antigen binding. Captured CD4+ cells were imaged with a fluorescence microscope to verify the chip specificity and efficiency. We achieved 70.2 +/- 6.5% capturing efficiency and 88.8 +/- 5.4% specificity for CD4+ T lymphocytes (n = 9 devices). Bright field images of the captured cells in the 24 mm × 4 mm × 50 μm microfluidic chip were obtained with the CCD sensor in one second. We achieved an inexpensive system that rapidly captures cells and images them using a lens-less CCD system. This microfluidic device can be modified for use in single cell detection utilizing a cheap light-emitting diode (LED) chip instead of a wide range CCD system.

Perfluorocarbon Particle Size Influences Magnetic Resonance Signal and Immunological Properties of Dendritic Cells

PubMed Central

Waiczies, Helmar; Lepore, Stefano; Janitzek, Nicole; Hagen, Ulrike; Seifert, Frank; Ittermann, Bernd; Purfürst, Bettina; Pezzutto, Antonio; Paul, Friedemann; Niendorf, Thoralf; Waiczies, Sonia

2011-01-01

The development of cellular tracking by fluorine (19F) magnetic resonance imaging (MRI) has introduced a number of advantages for following immune cell therapies in vivo. These include improved signal selectivity and a possibility to correlate cells labeled with fluorine-rich particles with conventional anatomic proton (1H) imaging. While the optimization of the cellular labeling method is clearly important, the impact of labeling on cellular dynamics should be kept in mind. We show by 19F MR spectroscopy (MRS) that the efficiency in labeling cells of the murine immune system (dendritic cells) by perfluoro-15-crown-5-ether (PFCE) particles increases with increasing particle size (560>365>245>130 nm). Dendritic cells (DC) are professional antigen presenting cells and with respect to impact of PFCE particles on DC function, we observed that markers of maturation for these cells (CD80, CD86) were also significantly elevated following labeling with larger PFCE particles (560 nm). When labeled with these larger particles that also gave an optimal signal in MRS, DC presented whole antigen more robustly to CD8+ T cells than control cells. Our data suggest that increasing particle size is one important feature for optimizing cell labeling by PFCE particles, but may also present possible pitfalls such as alteration of the immunological status of these cells. Therefore depending on the clinical scenario in which the 19F-labeled cellular vaccines will be applied (cancer, autoimmune disease, transplantation), it will be interesting to monitor the fate of these cells in vivo in the relevant preclinical mouse models. PMID:21811551

A solitary polypoid gastric metastasis 20 years after renal cell carcinoma: an event to be considered, and a brief review of the literature.

PubMed

Onorati, M; Petracco, G; Uboldi, P; Redaelli, D G; Romagnoli, S; Albertoni, M; Di Nuovo, F

2013-08-01

The incidence of gastric metastasis is 2.6%. Although all primary neoplasms can metastasize to the stomach, most originate from melanoma or breast and lung cancer. Their most common endoscopic appearance is a "volcano-like" polypoid mass covered by normal mucosa that may show a central ulceration. Renal cell carcinoma, clear cell type, is known to spread hematogenously, and isolated metastasis to the stomach is a rare event. In this report, we describe a gastric recurrence of RCC, clear-cell type, in a 80-year-old patient who had undergone nephrectomy 20 years before. We also performed a brief review of the literature to update the number of cases described to date. Metastatic involvement of the stomach should be suspected in any patient with a previous history of renal cell carcinoma, clear cell type, presenting with gastrointestinal symptoms, even if many years after nephrectomy. The peculiarity of our case is due to the very late presentation of the gastric metastasis. Only two cases of very late gastric metastases from RCC, clear cell type, have been described in the literature, to date.

Validation of a Postoperative Nomogram Predicting Recurrence in Patients with Conventional Clear Cell Renal Cell Carcinoma.

PubMed

Lee, Byron H; Feifer, Andrew; Feuerstein, Michael A; Benfante, Nicole E; Kou, Lei; Yu, Changhong; Kattan, Michael W; Russo, Paul

2018-01-01

Clear cell renal cell carcinoma (RCC) continues to be the most commonly diagnosed subtype and is associated with more aggressive behavior than papillary and chromophobe RCC. Predicting disease recurrence after surgical extirpation is important for counseling and targeting those at high risk for adjuvant therapy clinical trials. To validate a postoperative nomogram predicting 5-yr recurrence-free probability (RFP) for clinically localized clear cell RCC. We identified all patients who underwent nephrectomy for clinically localized clear cell RCC from 1990 to 2009 at Memorial Sloan Kettering Cancer Center. After excluding patients with bilateral renal masses, familial RCC syndromes, and T3c or T4 tumors due to the limited number, 1642 participants were available for analysis. Partial or radical nephrectomy. Disease recurrence was defined as any new tumor after nephrectomy or kidney cancer-specific mortality, whichever occurred first. A postoperative nomogram was used to calculate the predicted 5-yr RFP, and these values were compared with the actual 5-yr RFP. Nomogram performance was evaluated by concordance index and calibration plot. Median follow-up was 39 mo (interquartile range: 14-79 mo), and disease recurrence was observed in 50 patients. The nomogram concordance index was 0.81. The calibration curve showed that the nomogram underestimated the actual 5-yr RFP. We updated the nomogram by including the entire patient population, which maintained performance and significantly improved calibration. The updated clear cell RCC postoperative nomogram performed well in the combined cohort. Underestimation of actual 5-yr RFP by the original nomogram may be due to increased surgeon experience and other unknown variables. We updated a valuable prediction tool used for assessing the disease recurrence probability after nephrectomy for clear cell renal cell carcinoma. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Intuitiveness of Symbol Features for Air Traffic Management

NASA Technical Reports Server (NTRS)

Ngo, Mary Kim; Vu, Kim-Phuong L.; Thorpe, Elaine; Battiste, Vernol; Strybel, Thomas Z.

2012-01-01

We present the results of two online surveys asking participants to indicate what type of air traffic information might be conveyed by a number of symbols and symbol features (color, fill, text, and shape). The results of this initial study suggest that the well-developed concepts of ownership, altitude, and trajectory are readily associated with certain symbol features, while the relatively novel concept of equipage was not clearly associated with any specific symbol feature.

Urinary collecting system invasion is associated with poor survival in patients with clear-cell renal cell carcinoma.

PubMed

Bailey, George C; Boorjian, Stephen A; Ziegelmann, Matthew J; Westerman, Mary E; Lohse, Christine M; Leibovich, Bradley C; Cheville, John C; Thompson, R Houston

2017-04-01

To evaluate the prognostic significance of urinary collecting system invasion (UCSI) in a large series of patients with clear-cell renal cell carcinoma (RCC). Patients with clear-cell RCC treated with nephrectomy between 2001 and 2010 were reviewed from a prospectively maintained registry. One urological pathologist re-reviewed all slides. Cancer-specific survival was estimated using the Kaplan-Meier method, and associations of UCSI with death from RCC were evaluated using Cox models. Of the 859 patients with clear-cell RCC, 58 (6.8%) had UCSI. At last follow-up, 310 patients had died from RCC at a median of 1.8 years after surgery. The median follow-up for patients alive at last follow-up was 8.2 years. The estimated cancer-specific survival at 10 years after surgery for patients with UCSI was 17%, compared with 60% for patients without UCSI (P < 0.001). In a multivariable model, UCSI remained independently associated with an increased risk of death from RCC (hazard ratio 1.5; P = 0.018). Further, among patients with pT3 RCC, those with USCI had survival outcomes similar to those of patients with pT4 RCC. Collecting system invasion is associated with poor prognosis among patients with clear-cell RCC. If validated, consideration should be given to including UCSI in future staging systems. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

A New Approach to Automated Labeling of Internal Features of Hardwood Logs Using CT Images

Treesearch

Daniel L. Schmoldt; Pei Li; A. Lynn Abbott

1996-01-01

The feasibility of automatically identifying internal features of hardwood logs using CT imagery has been established previously. Features of primary interest are bark, knots, voids, decay, and clear wood. Our previous approach: filtered original CT images, applied histogram segmentation, grew volumes to extract 3-d regions, and applied a rule base, with Dempster-...

Ironing out the details of iron overload in myelofibrosis: Lessons from myelodysplastic syndromes.

PubMed

Carreau, Nicole; Tremblay, Douglas; Savona, Michael; Kremyanskaya, Marina; Mascarenhas, John

2016-09-01

Myelofibrosis (MF) and myelodysplastic syndrome (MDS) are hematopoietic stem cell disorders associated with cytopenias and red blood cell (RBC) transfusion dependence. Iron overload (IO) as a consequence of RBC transfusion dependence and its effect on outcomes in MF has not been formally studied. However, IO is a demonstrated poor prognostic feature in patients with MDS and congenital or acquired chronic anemias. Evidence that iron chelation therapy (ICT) reduces the deleterious effects of IO in MDS has led to speculation of benefit in MF. However, data supporting the use of ICT in MF is lacking. Neither disease has clear consensus guidelines for the use of ICT. Moreover, JAK-STAT inhibition, the cornerstone of MF treatment, often contributes to anemia and transfusional requirements. This manuscript reviews known and potential implications of IO in MF and highlights the need for prospective clinical investigations of ICT with consideration in the setting of JAK2 inhibitor therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arginase 2 Suppresses Renal Carcinoma Progression via Biosynthetic Cofactor Pyridoxal Phosphate Depletion and Increased Polyamine Toxicity.

PubMed

Ochocki, Joshua D; Khare, Sanika; Hess, Markus; Ackerman, Daniel; Qiu, Bo; Daisak, Jennie I; Worth, Andrew J; Lin, Nan; Lee, Pearl; Xie, Hong; Li, Bo; Wubbenhorst, Bradley; Maguire, Tobi G; Nathanson, Katherine L; Alwine, James C; Blair, Ian A; Nissim, Itzhak; Keith, Brian; Simon, M Celeste

2018-05-04

Kidney cancer, one of the ten most prevalent malignancies in the world, has exhibited increased incidence over the last decade. The most common subtype is "clear cell" renal cell carcinoma (ccRCC), which features consistent metabolic abnormalities, such as highly elevated glycogen and lipid deposition. By integrating metabolomics, genomic, and transcriptomic data, we determined that enzymes in multiple metabolic pathways are universally depleted in human ccRCC tumors, which are otherwise genetically heterogeneous. Notably, the expression of key urea cycle enzymes, including arginase 2 (ARG2) and argininosuccinate synthase 1 (ASS1), is strongly repressed in ccRCC. Reduced ARG2 activity promotes ccRCC tumor growth through at least two distinct mechanisms: conserving the critical biosynthetic cofactor pyridoxal phosphate and avoiding toxic polyamine accumulation. Pharmacological approaches to restore urea cycle enzyme expression would greatly expand treatment strategies for ccRCC patients, where current therapies only benefit a subset of those afflicted with renal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Function-oriented synthesis: biological evaluation of laulimalide analogues derived from a last step cross metathesis diversification strategy.

PubMed

Mooberry, Susan L; Hilinski, Michael K; Clark, Erin A; Wender, Paul A

2008-01-01

Laulimalide is a potent microtubule stabilizing agent and a promising anticancer therapeutic lead. The identification of stable, efficacious and accessible analogues is critical to clinically exploiting this novel lead. To determine which structural features of laulimalide are required for beneficial function and thus for accessing superior clinical candidates, a series of side chain analogues were prepared through a last step cross metathesis diversification strategy and their biological activities were evaluated. Five analogues, differing in potency from 233 nM to 7.9 muM, effectively inhibit cancer cell proliferation. Like laulimalide, they retain activity against multidrug resistant cells, stabilize microtubules and cause the formation of aberrant mitotic spindles, mitotic accumulation, Bcl-2 phosphorylation and initiation of apoptosis. Structural modifications in the C 23-C 27 dihydropyran side chain can be made without changing the overall mechanism of action, but it is clear that this subunit has more than a bystander role.

Imaging articular cartilage using second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Mansfield, Jessica C.; Winlove, C. Peter; Knapp, Karen; Matcher, Stephen J.

2006-02-01

Sub cellular resolution images of equine articular cartilage have been obtained using both second harmonic generation microscopy (SHGM) and two-photon fluorescence microscopy (TPFM). The SHGM images clearly map the distribution of the collagen II fibers within the extracellular matrix while the TPFM images show the distribution of endogenous two-photon fluorophores in both the cells and the extracellular matrix, highlighting especially the pericellular matrix and bright 2-3μm diameter features within the cells. To investigate the source of TPF in the extracellular matrix experiments have been carried out to see if it may originate from the proteoglycans. Pure solutions of the following proteoglycans hyaluronan, chondroitin sulfate and aggrecan have been imaged, only the aggrecan produced any TPF and here the intensity was not great enough to account for the TPF in the extracellular matrix. Also cartilage samples were subjected to a process to remove proteoglycans and cellular components. After this process the TPF from the samples had decreased by a factor of two, with respect to the SHG intensity.

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

PubMed

Turajlic, Samra; Xu, Hang; Litchfield, Kevin; Rowan, Andrew; Horswell, Stuart; Chambers, Tim; O'Brien, Tim; Lopez, Jose I; Watkins, Thomas B K; Nicol, David; Stares, Mark; Challacombe, Ben; Hazell, Steve; Chandra, Ashish; Mitchell, Thomas J; Au, Lewis; Eichler-Jonsson, Claudia; Jabbar, Faiz; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Lynch, Joanna; Fernando, Archana; Stamp, Gordon; Nye, Emma; Stewart, Aengus; Xing, Wei; Smith, Jonathan C; Escudero, Mickael; Huffman, Adam; Matthews, Nik; Elgar, Greg; Phillimore, Ben; Costa, Marta; Begum, Sharmin; Ward, Sophia; Salm, Max; Boeing, Stefan; Fisher, Rosalie; Spain, Lavinia; Navas, Carolina; Grönroos, Eva; Hobor, Sebastijan; Sharma, Sarkhara; Aurangzeb, Ismaeel; Lall, Sharanpreet; Polson, Alexander; Varia, Mary; Horsfield, Catherine; Fotiadis, Nicos; Pickering, Lisa; Schwarz, Roland F; Silva, Bruno; Herrero, Javier; Luscombe, Nick M; Jamal-Hanjani, Mariam; Rosenthal, Rachel; Birkbak, Nicolai J; Wilson, Gareth A; Pipek, Orsolya; Ribli, Dezso; Krzystanek, Marcin; Csabai, Istvan; Szallasi, Zoltan; Gore, Martin; McGranahan, Nicholas; Van Loo, Peter; Campbell, Peter; Larkin, James; Swanton, Charles

2018-04-19

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance. Copyright © 2018 Francis Crick Institute. Published by Elsevier Inc. All rights reserved.

MG63 cells behavior on rough polypyrrole scaffolds investigated by digital holographic microscopy

NASA Astrophysics Data System (ADS)

Mihailescu, M.; Matei, A.; Acasandrei, A.; Popescu, R. C.; Paun, I. A.; Dinescu, Maria

2014-07-01

The study of cells-substrate interaction became a stringent subject in the past decades, since an increasing variety of new materials and methods have been involved in tissue engineering or implants techniques. The investigation of this interaction using optical methods is a challenge, especially since these substrates are not optically polished. Due to their roughness in the micrometric or submicrometric range, the polymeric substrates offers good conditions for cells adhesion, but the characterization of cells properties can be hindered. In this study, we use Polypyrrole thin films, acting as substrates for cultured osteoblast-like MG63 cells having applications in tissue engineering for in vivo-like scaffolds. As characterization technique, we chose digital holographic microscopy, a single-shot technique, to obtain quantitative information about the sample features in a plane perpendicular to the substrate. Different parameters were tested in the experimental setup with the aim of finding the optimal conditions for details visualization. The reconstructed 3D images were filtered using a combination of analytical and implicit functions from MATLAB to exclude small/large objects, which correspond to Polypyrrole droplets to clearly identify the cells contour for quantitative measurements regarding their dimensions. These data were correlated with the effects on osteoblasts viability and differentiation. Also, the thickness and the refractive index of the substrate were determined using the decoupling procedure.

Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor

PubMed Central

2012-01-01

Abstract Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643 PMID:22937790

Microscopic endometrial perivascular epithelioid cell nodules: a case report with the earliest presentation of a uterine perivascular epithelioid cell tumor.

PubMed

Fang, Chia-Lang; Lin, Yun-Ho; Chen, Wei-Yu

2012-09-03

Perivascular epithelioid cell (PEC) tumors (PEComas) are a family of related mesenchymal tumors composed of PECs which co-express melanocytic and smooth muscle markers. Although their distinctive histologic, immunohistochemical, ultrastructural, and genetic features have been clearly demonstrated, their histogenesis and normal counterpart remain largely unknown. Precursor lesions of PEComas have rarely been reported. We herein describe a tuberous sclerosis patient with microscopic PEC nodules in the endometrium of adenomyosis, pelvic endometriosis, an ovarian endometriotic cyst, and the endometrium of the uterine cavity. The nodules showed a mixture of spindle-shaped and epithelioid cells concentrically arranged around small arteries. The cells exhibited uniform nuclei, light eosinophilic cytoplasm, and immunoreactivity with HMB-45 and CD10. Some nodules revealed continuity with a PEComa in the myometrium. These findings support microscopic endometrial PEC nodules possibly being precursor lesions of uterine PEComas. The wide distribution of the nodules in the pelvis may be related to the multicentricity of PEComas in tuberous sclerosis patients. Owing to the immunoreactivity with CD10, microscopic endometrial PEC nodules may be misinterpreted as endothelial stromal cells unless melanocytic markers are stained. To the best of our knowledge, this is a case with the earliest manifestation of PEC lesions occurring in the endometrium. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9658280017862643.

Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression

PubMed Central

Lowe, Donna; Raj, Kenneth

2014-01-01

Age is undoubtedly a major risk factor for heart disease. However, the reason for this is not entirely clear. In the course of our investigation into the mechanism of radiation-induced cardiovascular disease, we made several unexpected findings that inform us on this question. We observed that human coronary endothelial cells, while being able to initiate repair of radiation-induced DNA damage, often fail to complete the repair and become senescent. Such radiation-induced cellular aging occurs through a mutation-independent route. Endothelial cells that aged naturally through replication or as a result of radiation exhibited indistinguishable characteristics. The promoter regions of the CD44 gene in aging endothelial cells become demethylated, and the proteins are highly expressed on the cell surface, making the cells adhesive for monocytes. Adhesion is a cardinal feature that recruits monocytes to the endothelium, allowing them to infiltrate the vessel wall and initiate atherosclerosis. The epigenetic activation of CD44 expression is particularly significant as it causes persistent elevated CD44 protein expression, making senescent endothelial cells chronically adhesive. In addition to understanding why cardiovascular disease increases with age, these observations provide insights into the puzzling association between radiation and cardiovascular disease and highlight the need to consider premature aging as an additional risk of radiation to human health. PMID:25059316

Submicrostructure and typing of female genital condylomata.

PubMed

He, Y C; Shen, L S; Xie, Z J; Yang, C L; Li, H; Zheng, Y; Zhu, G C; Zhao, S Z; Wang, C X; Zhang, J H

1993-04-01

Thirty biopsies from female genital condylomata were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to study structural characteristics and typing of condylomata. It was found that cytoplasmic clearing was marked in acuminate condylomata, diffuse interstitial and epithelial proliferation in nodular condylomata (flat condylomata), and invagination of the lesions into the interstitial tissue or glandular ducts in endophytic condylomata. In nodular condylomata, SEM also showed some structural features similar to those of intra-epithelial neoplasia. Microridges on the surface of squamous cells had villiform of granular changes. On the surface of a percentage of squamous or columnar cells, there were holes with a diameter of about 3 to 5 microns. A number of giant cells were seen among other cells. The cervical squamatization zone contained groups of special cells covered with dense microvilli. TEM of nodular condylomata revealed some pictures resembling active proliferation of tumor cells, such as enlarged or irregular nuclei (large N/C ratio), evaginated or invaginated nuclear membranes, condensed chromatin attached to the inner part of the nuclear membrane, transparent nucleoplasm, and frequent nucleosomes and karyokinesis. Virus particles with the morphological characteristics of HPV (naked hexagon-like particles with an average diameter of 45-50 nm) were seen in some nuclei with markedly condensed chromatin. It is suggested that HPV-induced genital condylomata, especially nodular one (flat condylomata), entail a potential progression to malignancy.

Imprint cytologic features in renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in an adult: a case report.

PubMed

Yamaguchi, Tadanori; Kuroda, Naoto; Imamura, Yoshiaki; Hes, Ondrej; Kawada, Takako; Nakayama, Keizou

2009-01-01

Adult-onset renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion is a very rare tumor. To date, there are no reports on immunocytochemical study of the primary tumor. We describe such a case that we diagnosed by immunocytochemistry of imprint cytology material. A 46-year-old man was found to have a mass in the lower pole of the right kidney. Magnetic resonance imaging (MRI) T2-weighted images showed a hypointense area in the tumor, and papillary RCC was suspected. Imprint cytology showed tumor cells that were isolated or arranged in large or small papillary clusters. Irregularly shaped large oval nuclei, finely granular chromatin and a single large nucleolus were noted. Cytoplasm was abundant and admixed with clear and granular eosinophilic patterns and scattered large vacuolated cells. Almost all tumor cells diffusely expressed immunocytochemical reactivity to TFE3 protein. Hyaline nodules were observed in the stroma. Ultrastructurally, neoplastic cells contained rhomboid crystals identical to those of alveolar soft part sarcoma. The immunocytochemistry of TFE3 protein may be a powerful tool for accurate diagnosis when RCC associated with Xp11.2 translocation/TFE3 gene fusion is suspected by imprint cytology even in adult-onset cases, and cytotechnologists should accurately recognize cytologic findings of this tumor.

Bridging the Gap: From 2D Cell Culture to 3D Microengineered Extracellular Matrices.

PubMed

Li, Yanfen; Kilian, Kristopher A

2015-12-30

Historically the culture of mammalian cells in the laboratory has been performed on planar substrates with media cocktails that are optimized to maintain phenotype. However, it is becoming increasingly clear that much of biology discerned from 2D studies does not translate well to the 3D microenvironment. Over the last several decades, 2D and 3D microengineering approaches have been developed that better recapitulate the complex architecture and properties of in vivo tissue. Inspired by the infrastructure of the microelectronics industry, lithographic patterning approaches have taken center stage because of the ease in which cell-sized features can be engineered on surfaces and within a broad range of biocompatible materials. Patterning and templating techniques enable precise control over extracellular matrix properties including: composition, mechanics, geometry, cell-cell contact, and diffusion. In this review article we explore how the field of engineered extracellular matrices has evolved with the development of new hydrogel chemistry and the maturation of micro- and nano- fabrication. Guided by the spatiotemporal regulation of cell state in developing tissues, techniques for micropatterning in 2D, pseudo-3D systems, and patterning within 3D hydrogels will be discussed in the context of translating the information gained from 2D systems to synthetic engineered 3D tissues. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

PubMed Central

Mangolini, Alessandra; Bonon, Anna; Volinia, Stefano; Lanza, Giovanni; Gambari, Roberto; Pinton, Paolo; Russo, Gian Rosario; del Senno, Laura; Dell’Atti, Lucio; Aguiari, Gianluca

2014-01-01

Renal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs), which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma. PMID:25426415

Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern.

PubMed

Haller, Florian; Knopf, Jasmin; Ackermann, Anne; Bieg, Matthias; Kleinheinz, Kortine; Schlesner, Matthias; Moskalev, Evgeny A; Will, Rainer; Satir, Ali Abdel; Abdelmagid, Ibtihalat E; Giedl, Johannes; Carbon, Roman; Rompel, Oliver; Hartmann, Arndt; Wiemann, Stefan; Metzler, Markus; Agaimy, Abbas

2016-04-01

Neoplasms with a myopericytomatous pattern represent a morphological spectrum of lesions encompassing myopericytoma of the skin and soft tissue, angioleiomyoma, myofibromatosis/infantile haemangiopericytoma and putative neoplasms reported as malignant myopericytoma. Lack of reproducible phenotypic and genetic features of malignant myopericytic neoplasms have prevented the establishment of myopericytic sarcoma as an acceptable diagnostic category. Following detection of a LMNA-NTRK1 gene fusion in an index case of paediatric haemangiopericytoma-like sarcoma by combined whole-genome and RNA sequencing, we identified three additional sarcomas harbouring NTRK1 gene fusions, termed 'spindle cell sarcoma, NOS with myo/haemangiopericytic growth pattern'. The patients were two children aged 11 months and 2 years and two adults aged 51 and 80 years. While the tumours of the adults were strikingly myopericytoma-like, but with clear-cut atypical features, the paediatric cases were more akin to infantile myofibromatosis/haemangiopericytoma. All cases contained numerous thick-walled dysplastic-like vessels with segmental or diffuse nodular myxohyaline myo-intimal proliferations of smooth muscle actin-positive cells, occasionally associated with thrombosis. Immunohistochemistry showed variable expression of smooth muscle actin and CD34, but other mesenchymal markers, including STAT6, were negative. This study showed a novel variant of myo/haemangiopericytic sarcoma with recurrent NTRK1 gene fusions. Given the recent introduction of a novel therapeutic approach targeting NTRK fusion-positive neoplasms, recognition of this rare but likely under-reported sarcoma variant is strongly encouraged. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease.

PubMed

Manuel, Sharrón L; Schell, Todd D; Acheampong, Edward; Rahman, Saifur; Khan, Zafar K; Jain, Pooja

2009-11-01

HTLV-1 is the etiologic agent of a debilitating neurologic disorder, HAM/TSP. This disease features a robust immune response including the oligoclonal expansion of CD8+ CTLs specific for the viral oncoprotein Tax. The key pathogenic process resulting in the proliferation of CTLs and the presentation of Tax peptide remains uncharacterized. We have investigated the role of APCs, particularly DCs, in priming of the anti-Tax CTL response under in vitro and in vivo conditions. We investigated two routes (direct vs. indirect) of Tax presentation using live virus, infected primary CD4+/CD25+ T cells, and the CD4+ T cell line (C8166, a HTLV-1-mutated line that only expresses Tax). Our results indicated that DCs are capable of priming a pronounced Tax-specific CTL response in cell cultures consisting of naïve PBLs as well as in HLA-A*0201 transgenic mice (line HHD II). DCs were able to direct the presentation of Tax successfully through infected T cells, live virus, and cell-free Tax. These observations were comparable with those made with a known stimulant of DC maturation, a combination of CD40L and IFN-gamma. Our studies clearly establish a role for this important immune cell component in HTLV-1 immuno/neuropathogenesis and suggest that modulation of DC functions could be an important tool for therapeutic interventions.

Periodontitis aggravated pancreatic β-cell dysfunction in diabetic mice through interleukin-12 regulation on Klotho.

PubMed

Liu, Yihua; Zhang, Qiuli

2016-05-01

Recent studies have shown that periodontitis can contribute to adipose tissue inflammation and subsequent systemic insulin resistance in the obese rat model. However, the related inflammatory mechanism is not yet clear. The present study aims to investigate the effects of periodontitis on the function of pancreatic β-cells with pro-inflammatory cytokines-related immune mechanism in a mouse model. C57BL/6-db/db and inbred C57BL/6 mice were chosen here to establish a mouse model with periodontitis, which was induced by ligatures for 8 weeks. Glucose-stimulated insulin secretion was introduced to evaluate the function of pancreatic islets and β-cells. Serum levels of pro-inflammatory cytokines and Klotho were also measured, and the correlation between immunostimulation and Klotho level was deeply investigated in vitro. Pancreatic β-cell failure, with insulin resistance, was observed in db/db mice, while periodontitis could aggravate β-cell dysfunction-related features. Serum levels of interleukin (IL)-12 and Klotho showed a negatively synergistic change, whereas the expression of Klotho was also inhibited under IL-12 treatment in MIN6 β-cells or isolated islets. Furthermore, IL-12-induced immune stimulation and also decreased insulin secretion were proven to be reversed by Klotho overexpression. Periodontitis aggravated pancreatic β-cell failure in diabetic mice. Further in vitro studies showed IL-12 regulation on Klotho, while Klotho also acted as an inhibitor on IL-12, indicating the potential of Klotho for preserving pancreatic β-cell function in diabetes.

Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease

PubMed Central

Manuel, Sharrón L.; Schell, Todd D.; Acheampong, Edward; Rahman, Saifur; Khan, Zafar K.; Jain, Pooja

2009-01-01

HTLV-1 is the etiologic agent of a debilitating neurologic disorder, HAM/TSP. This disease features a robust immune response including the oligoclonal expansion of CD8+ CTLs specific for the viral oncoprotein Tax. The key pathogenic process resulting in the proliferation of CTLs and the presentation of Tax peptide remains uncharacterized. We have investigated the role of APCs, particularly DCs, in priming of the anti-Tax CTL response under in vitro and in vivo conditions. We investigated two routes (direct vs. indirect) of Tax presentation using live virus, infected primary CD4+/CD25+ T cells, and the CD4+ T cell line (C8166, a HTLV-1-mutated line that only expresses Tax). Our results indicated that DCs are capable of priming a pronounced Tax-specific CTL response in cell cultures consisting of naïve PBLs as well as in HLA-A*0201 transgenic mice (line HHD II). DCs were able to direct the presentation of Tax successfully through infected T cells, live virus, and cell-free Tax. These observations were comparable with those made with a known stimulant of DC maturation, a combination of CD40L and IFN-γ. Our studies clearly establish a role for this important immune cell component in HTLV-1 immuno/neuropathogenesis and suggest that modulation of DC functions could be an important tool for therapeutic interventions. PMID:19656902

Method for evaluation of human induced pluripotent stem cell quality using image analysis based on the biological morphology of cells.

PubMed

Wakui, Takashi; Matsumoto, Tsuyoshi; Matsubara, Kenta; Kawasaki, Tomoyuki; Yamaguchi, Hiroshi; Akutsu, Hidenori

2017-10-01

We propose an image analysis method for quality evaluation of human pluripotent stem cells based on biologically interpretable features. It is important to maintain the undifferentiated state of induced pluripotent stem cells (iPSCs) while culturing the cells during propagation. Cell culture experts visually select good quality cells exhibiting the morphological features characteristic of undifferentiated cells. Experts have empirically determined that these features comprise prominent and abundant nucleoli, less intercellular spacing, and fewer differentiating cellular nuclei. We quantified these features based on experts' visual inspection of phase contrast images of iPSCs and found that these features are effective for evaluating iPSC quality. We then developed an iPSC quality evaluation method using an image analysis technique. The method allowed accurate classification, equivalent to visual inspection by experts, of three iPSC cell lines.

Identification of the feature that causes the I-band secondary maximum of a Type Ia supernova

NASA Astrophysics Data System (ADS)

Jack, D.; Baron, E.; Hauschildt, P. H.

2015-06-01

We obtained a time series of spectra covering the secondary maximum in the I band of the bright Type Ia supernova 2014J in M82 with the TIGRE telescope. Comparing the observations with theoretical models calculated with the time dependent extension of the PHOENIX code, we identify the feature that causes the secondary maximum in the I-band light curve. Fe II 3d6(3D)4s-3d6(5D)4p and similar high-excitation transitions produce a blended feature at ˜7500 Å, which causes the rise of the light curve towards the secondary maximum. The series of observed spectra of SN 2014J and archival data of SN 2011fe confirm this conclusion. We further studied the plateau phase of the R-band light curve of SN 2014J and searched for features which contribute to the flux. The theoretical models do not clearly indicate a new feature that may cause the R-band plateau phase. However, Co II features in the range of 6500-7000 Å and the Fe II feature of the I band are clearly seen in the theoretical spectra, but do not appear to provide all of the flux necessary for the R-band plateau.

In vitro cellular responses to silicon carbide nanoparticles: impact of physico-chemical features on pro-inflammatory and pro-oxidative effects

NASA Astrophysics Data System (ADS)

Pourchez, Jérémie; Forest, Valérie; Boumahdi, Najih; Boudard, Delphine; Tomatis, Maura; Fubini, Bice; Herlin-Boime, Nathalie; Leconte, Yann; Guilhot, Bernard; Cottier, Michèle; Grosseau, Philippe

2012-10-01

Silicon carbide is an extremely hard, wear resistant, and thermally stable material with particular photoluminescence and interesting biocompatibility properties. For this reason, it is largely employed for industrial applications such as ceramics. More recently, nano-sized SiC particles were expected to enlarge their use in several fields such as composite supports, power electronics, biomaterials, etc. However, their large-scaled development is restricted by the potential toxicity of nanoparticles related to their manipulation and inhalation. This study aimed at synthesizing (by laser pyrolysis or sol-gel methods), characterizing physico-chemical properties of six samples of SiC nanopowders, then determining their in vitro biological impact(s). Using a macrophage cell line, toxicity was assessed in terms of cell membrane damage (LDH release), inflammatory effect (TNF-α production), and oxidative stress (reactive oxygen species generation). None of the six samples showed cytotoxicity while remarkable pro-oxidative reactions and inflammatory response were recorded, whose intensity appears related to the physico-chemical features of nano-sized SiC particles. In vitro data clearly showed an impact of the extent of nanoparticle surface area and the nature of crystalline phases (α-SiC vs. β-SiC) on the TNF-α production, a role of surface iron on free radical release, and of the oxidation state of the surface on cellular H2O2 production.

Using local chromatin structure to improve CRISPR/Cas9 efficiency in zebrafish.

PubMed

Chen, Yunru; Zeng, Shiyang; Hu, Ruikun; Wang, Xiangxiu; Huang, Weilai; Liu, Jiangfang; Wang, Luying; Liu, Guifen; Cao, Ying; Zhang, Yong

2017-01-01

Although the CRISPR/Cas9 has been successfully applied in zebrafish, considerable variations in efficiency have been observed for different gRNAs. The workload and cost of zebrafish mutant screening is largely dependent on the mutation rate of injected embryos; therefore, selecting more effective gRNAs is especially important for zebrafish mutant construction. Besides the sequence features, local chromatin structures may have effects on CRISPR/Cas9 efficiency, which remain largely unexplored. In the only related study in zebrafish, nucleosome organization was not found to have an effect on CRISPR/Cas9 efficiency, which is inconsistent with recent studies in vitro and in mammalian cell lines. To understand the effects of local chromatin structure on CRISPR/Cas9 efficiency in zebrafish, we first determined that CRISPR/Cas9 introduced genome editing mainly before the dome stage. Based on this observation, we reanalyzed our published nucleosome organization profiles and generated chromatin accessibility profiles in the 256-cell and dome stages using ATAC-seq technology. Our study demonstrated that chromatin accessibility showed positive correlation with CRISPR/Cas9 efficiency, but we did not observe a clear correlation between nucleosome organization and CRISPR/Cas9 efficiency. We constructed an online database for zebrafish gRNA selection based on local chromatin structure features that could prove beneficial to zebrafish homozygous mutant construction via CRISPR/Cas9.

Clear cell hidradenocarcinoma of the ear helix: report of primary ear helix adnexal carcinoma with regional lymph node metastasis.

PubMed

Bae, Tae Hui; Kang, Shin Hyuk; Kim, Han Koo; Kim, Woo Seob; Kim, Mi Kyung

2014-07-01

Clear cell hidradenocarcinoma is a rare tumor of eccrine sweat gland origin that has a predilection for the head and neck. It has an indolent growth pattern and a higher incidence of regional and distant metastases. Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. We report a case of an 89-year-old female patient with clear cell hidradenocarcinoma manifesting in the right ear helix that metastasized to the right parotid gland who was treated by wide local excision and radiation therapy.

Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-06-11

BRCA Rearrangement; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Tumor; Ovarian Seromucinous Carcinoma; Ovarian Serous Tumor; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.

PubMed

Sharrow, Allison C; Perkins, Brandy; Collector, Michael I; Yu, Wayne; Simons, Brian W; Jones, Richard J

2016-08-01

The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer. We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3. Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

Examination of body fluids.

PubMed

Feldman, B F; Ruehl, W W

1984-04-01

In dogs, the pericardial sac contains about 0.3 ml, and the pleural and peritoneal cavities 0-15 ml of clear, straw-colored fluid of pH 7.4, specific gravity 1.016, protein content less than 3.0 g/dl and cell count less than 3000/microliter. Fat can be cleared from chylous fluid with NaOH and ether. Inflammation is indicated by a cell count greater than 3000/microliter. Amylase levels in peritoneal fluid are elevated in necrotizing pancreatitis. The percentage of polymorphonuclear WBC exceeds 50% in bacterial inflammations. Normal joints contain less than 1 ml highly viscid, clear or straw-colored synovial fluid with less than 1000 nucleated cells/microliter. Synovial fluid becomes flocculent and less viscid in septic and occasionally in immune-mediated arthritis, often with cell counts greater than 75,000/microliter, with 75-90% polymorphonuclear WBC. Cerebrospinal fluid is normally acellular, clear and colorless but may be red, yellow or brown with intracranial hematomas. Viral or aseptic meningitis is characterized by mononuclear cell counts of less than 500/microliter. In acute bacterial meningitis, nucleated cell counts are greater than 1000/microliter, with most being polymorphonuclear WBC. Gram staining of cerebrospinal fluid is not useful.

Origin of eukaryotes from within archaea, archaeal eukaryome and bursts of gene gain: eukaryogenesis just made easier?

PubMed Central

Koonin, Eugene V.

2015-01-01

The origin of eukaryotes is a fundamental, forbidding evolutionary puzzle. Comparative genomic analysis clearly shows that the last eukaryotic common ancestor (LECA) possessed most of the signature complex features of modern eukaryotic cells, in particular the mitochondria, the endomembrane system including the nucleus, an advanced cytoskeleton and the ubiquitin network. Numerous duplications of ancestral genes, e.g. DNA polymerases, RNA polymerases and proteasome subunits, also can be traced back to the LECA. Thus, the LECA was not a primitive organism and its emergence must have resulted from extensive evolution towards cellular complexity. However, the scenario of eukaryogenesis, and in particular the relationship between endosymbiosis and the origin of eukaryotes, is far from being clear. Four recent developments provide new clues to the likely routes of eukaryogenesis. First, evolutionary reconstructions suggest complex ancestors for most of the major groups of archaea, with the subsequent evolution dominated by gene loss. Second, homologues of signature eukaryotic proteins, such as actin and tubulin that form the core of the cytoskeleton or the ubiquitin system, have been detected in diverse archaea. The discovery of this ‘dispersed eukaryome’ implies that the archaeal ancestor of eukaryotes was a complex cell that might have been capable of a primitive form of phagocytosis and thus conducive to endosymbiont capture. Third, phylogenomic analyses converge on the origin of most eukaryotic genes of archaeal descent from within the archaeal evolutionary tree, specifically, the TACK superphylum. Fourth, evidence has been presented that the origin of the major archaeal phyla involved massive acquisition of bacterial genes. Taken together, these findings make the symbiogenetic scenario for the origin of eukaryotes considerably more plausible and the origin of the organizational complexity of eukaryotic cells more readily explainable than they appeared until recently. PMID:26323764

High expression of SALL4 and fascin, and loss of E-cadherin expression in undifferentiated/dedifferentiated carcinomas of the endometrium

PubMed Central

Onder, Semen; Taskin, Orhun Cig; Sen, Fatma; Topuz, Samet; Kucucuk, Seden; Sozen, Hamdullah; Ilhan, Ridvan; Tuzlali, Sitki; Yavuz, Ekrem

2017-01-01

Abstract Undifferentiated/dedifferentiated endometrial carcinomas (UCE/DCEs) of the endometrium are rare tumors with poor prognosis. There are few clinicopathologic studies with detailed immunohistochemical analysis regarding UCE/DCEs. We evaluated the diagnostic value of a selected tumor stem-cell marker and epithelial-mesenchymal transition (EMT) markers, in addition to previously studied markers in identifying UCE/DCEs from other types of high-grade endometrial carcinomas. Eleven cases of UCE/DCEs with complete clinical follow-up that were diagnosed between 2006 and 2015 were included in the study. For immunohistochemical comparison, 11 clinically matched cases for each type of other high-grade endometrial carcinomas (high-grade endometrioid (F3-EC), serous [SC], and clear cell carcinoma [CCC]) were used as a control group. An immunohistochemical analysis including fascin, SALL4, E-cadherin, and β-catenin, in addition to epithelial and neuroendocrine markers was performed in each case. The majority of UCE/DCEs displayed diffuse expression of fascin (81.9%) and loss of E-cadherin expression (54.5%). SALL4 expression was detected in 36.3% of the UCE/DCE cases. SALL4 expression was significantly more frequent in UCE/DCEs than all other high-grade carcinomas (P < 0.001). Loss of E-cadherin and fascin expression was significantly more frequent in UCE/DCEs than high-grade endometrioid and clear cell adenocarcinomas (P = 0.012, 0.014 and P = 0.01, 0.003, respectively). We suggest that loss of E-cadherin expression together with fascin and SALL4 immunopositivity in addition to morphologic features have an impact in differential diagnosis of UCE/DCEs from other high-grade endometrial carcinomas. PMID:28272224

Identification of molecular tumor markers in renal cell carcinomas with TFE3 protein expression by RNA sequencing.

PubMed

Pflueger, Dorothee; Sboner, Andrea; Storz, Martina; Roth, Jasmine; Compérat, Eva; Bruder, Elisabeth; Rubin, Mark A; Schraml, Peter; Moch, Holger

2013-11-01

TFE3 translocation renal cell carcinoma (tRCC) is defined by chromosomal translocations involving the TFE3 transcription factor at chromosome Xp11.2. Genetically proven TFE3 tRCCs have a broad histologic spectrum with overlapping features to other renal tumor subtypes. In this study, we aimed for characterizing RCC with TFE3 protein expression. Using next-generation whole transcriptome sequencing (RNA-Seq) as a discovery tool, we analyzed fusion transcripts, gene expression profile, and somatic mutations in frozen tissue of one TFE3 tRCC. By applying a computational analysis developed to call chimeric RNA molecules from paired-end RNA-Seq data, we confirmed the known TFE3 translocation. Its fusion partner SFPQ has already been described as fusion partner in tRCCs. In addition, an RNA read-through chimera between TMED6 and COG8 as well as MET and KDR (VEGFR2) point mutations were identified. An EGFR mutation, but no chromosomal rearrangements, was identified in a control group of five clear cell RCCs (ccRCCs). The TFE3 tRCC could be clearly distinguished from the ccRCCs by RNA-Seq gene expression measurements using a previously reported tRCC gene signature. In validation experiments using reverse transcription-PCR, TMED6-COG8 chimera expression was significantly higher in nine TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in 24 ccRCCs (P < .001) and 22 papillary RCCs (P < .05-.07). Immunohistochemical analysis of selected genes from the tRCC gene signature showed significantly higher eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) and Contactin 3 (CNTN3) expression in 16 TFE3 translocated and six TFE3-expressing/non-translocated RCCs than in over 200 ccRCCs (P < .0001, both).

Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics

PubMed Central

Lin, Sabrina C.; Bays, Brett C.; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

2016-01-01

There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells. PMID:26848582

Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics.

PubMed

Zahedi, Atena; On, Vincent; Lin, Sabrina C; Bays, Brett C; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

2016-01-01

There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells.

Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm.

PubMed

Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning.

Dynamic Association with Donor Cell Filopodia and Lipid-Modification Are Essential Features of Wnt8a during Patterning of the Zebrafish Neuroectoderm

PubMed Central

Luz, Marta; Spannl-Müller, Stephanie; Özhan, Günes; Kagermeier-Schenk, Birgit; Rhinn, Muriel; Weidinger, Gilbert; Brand, Michael

2014-01-01

Background Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. Results We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. Conclusions Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning. PMID:24427298

An intraventricular clear cell meningioma revealed by an inflammatory syndrome in a male adult: a case report.

PubMed

Cassereau, J; Lavigne, C; Michalak-Provost, S; Ghali, A; Dubas, F; Fournier, H D

2008-07-01

Intraventricular meningiomas are infrequent intracranial tumors. Clinical symptoms are mainly due to an increased intracranial pressure or a direct pressure on the surrounding brain structures. Inflammatory syndrome was described in some patients with chordoid meningiomas. Here we report a case of right intraventricular clear cell meningioma in a 50-year-old man who presented with fever, headache, and inflammatory syndrome. Clinical and biological normalization was rapidly obtained after tumor removal. Immunohistochemical examination showed tumor cells and lymphocytes positivity for the pyrogenic cytokine interleukin-6, with a same intensity. To our knowledge, this is the first case described in the literature concerning an adult man with an intraventricular clear cell meningioma associated with a systemic inflammatory syndrome.

Comprehensive meta-analysis of Signal Transducers and Activators of Transcription (STAT) genomic binding patterns discerns cell-specific cis-regulatory modules

PubMed Central

2013-01-01

Background Cytokine-activated transcription factors from the STAT (Signal Transducers and Activators of Transcription) family control common and context-specific genetic programs. It is not clear to what extent cell-specific features determine the binding capacity of seven STAT members and to what degree they share genetic targets. Molecular insight into the biology of STATs was gained from a meta-analysis of 29 available ChIP-seq data sets covering genome-wide occupancy of STATs 1, 3, 4, 5A, 5B and 6 in several cell types. Results We determined that the genomic binding capacity of STATs is primarily defined by the cell type and to a lesser extent by individual family members. For example, the overlap of shared binding sites between STATs 3 and 5 in T cells is greater than that between STAT5 in T cells and non-T cells. Even for the top 1,000 highly enriched STAT binding sites, ~15% of STAT5 binding sites in mouse female liver are shared by other STATs in different cell types while in T cells ~90% of STAT5 binding sites are co-occupied by STAT3, STAT4 and STAT6. In addition, we identified 116 cis-regulatory modules (CRM), which are recognized by all STAT members across cell types defining a common JAK-STAT signature. Lastly, in liver STAT5 binding significantly coincides with binding of the cell-specific transcription factors HNF4A, FOXA1 and FOXA2 and is associated with cell-type specific gene transcription. Conclusions Our results suggest that genomic binding of STATs is primarily determined by the cell type and further specificity is achieved in part by juxtaposed binding of cell-specific transcription factors. PMID:23324445

Elevated Na+/H+ exchanger-1 expression enhances the metastatic collective migration of head and neck squamous cell carcinoma cells.

PubMed

Kaminota, Teppei; Yano, Hajime; Shiota, Kohei; Nomura, Noriko; Yaguchi, Haruna; Kirino, Yui; Ohara, Kentaro; Tetsumura, Issei; Sanada, Tomoyoshi; Ugumori, Toru; Tanaka, Junya; Hato, Naohito

2017-04-22

Cancer cells can migrate as collectives during invasion and/or metastasis; however, the precise molecular mechanisms of this form of migration are less clear compared with single cell migration following epithelial-mesenchymal transition. Elevated Na + /H + exchanger1 (NHE1) expression has been suggested to have malignant roles in a number of cancer cell lines and in vivo tumor models. Furthermore, a metastatic human head and neck squamous cell carcinoma (HNSCC) cell line (SASL1m) that was isolated based on its increased metastatic potential also exhibited higher NHE1 expression than its parental line SAS. Time-lapse video recordings indicated that both cell lines migrate as collectives, although with different features, e.g., SASL1m was much more active and changed the direction of migration more frequently than SAS cells, whereas locomotive activities were comparable. SASL1m cells also exhibited higher invasive activity than SAS in Matrigel invasion assays. shRNA-mediated NHE1 knockdown in SASL1m led to reduced locomotive and invasive activities, suggesting a critical role for NHE1 in the collective migration of SASL1m cells. SASL1m cells also exhibited a higher metastatic rate than SAS cells in a mouse lymph node metastasis model, while NHE1 knockdown suppressed in vivo SASL1m metastasis. Finally, elevated NHE1 expression was observed in human HNSCC tissue, and Cariporide, a specific NHE1 inhibitor, reduced the invasive activity of SASL1m cells, implying NHE1 could be a target for anti-invasion/metastasis therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

IMP3 Expression in Borderline Tumors of the Ovary.

PubMed

El-Balat, Ahmed; Sänger, Nicole; Karn, Thomas; Becker, Sven; Holtrich, Uwe; Muallem, Zelal; Arsenic, Ruza

2017-02-01

Borderline ovarian tumors (BOTs) have a less aggressive behavior than invasive epithelial ovarian tumors. Still some patients relapse or succumb to disease. Molecular markers that reliably predict prognosis are lacking. Insulin-like growth factor II mRNA-binding protein (IMP3) has been suggested as a prognostic marker in colorectal, hepatocellular, and ovarian clear-cell carcinomas. We analyzed the expression of IMP3 by immunohistochemistry in a cohort of 140 BOT and its association with histopathological features. We found no association of IMP3 expression with patients' age, FIGO stage, microinvasion, and presence of implants. In contrast, IMP3 expression correlated to mucinous subtype of BOTs (42.2% vs. 9.5% among other subtypes) (p<0.001). IMP3 expression was found to be associated with the presence of in situ carcinoma in MBOT, but not in other subtypes (p=0.021). Expression of IMP3 in BOT is associated with the mucinous subtype and may serve as an early indicator for the development of malignant features. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Genetic instability of 3p12-p21-specific microsatellite sequences in renal cell carcinoma.

PubMed

Willers, C P; Siebert, R; Bardenheuer, W; Lux, A; Michaelis, S; Seeber, S; Luboldt, H J; Opalka, B; Schütte, J

1996-04-01

To determine the role of structural alterations of human chromosome region 3p12-p21 in the possible inactivation of one or more tumour-suppressor genes in the pathogenesis of renal cell carcinoma (RCC), lung cancer and other neoplasms. As microsatellite instability (MI), in particular MI with loss of heterozygosity (LOH), may indicate putative tumour-suppressor gene loci, 20 kidney tumours, including 14 clear cell carcinomas and six non-clear cell neoplasms, were investigated with 10 polymorphic simple sequence-repeat markers spanning 3p12-p21. Six of these markers map to the region of deletion flanked by markers D3S1285 and D3S1295 bracketing the t(3;8) translocation break-point in 3p14.2 of hereditary RCC. Twelve of 14 clear cell RCCs displayed MI for at least one locus, as opposed to none of the non-clear cell tumours (P = 0.001). Locus D3S1274 in 3p13 located in the region deleted in lung cancer line U2020 and loci D3S1313 and D3S1300 in 3p14.3 characterized common regions of instability and LOH. Two patients with RCC who also had lung cancer and colon cancer, respectively, showed LOH at D3S1313 or D3S1300 as the only alterations of their kidney tumours. These results suggest that human chromosome region 3p14.3 distal to the hereditary t(3;8) translocation breakpoint and the region deleted in the U2020 lung cancer cell line might be involved in the tumorigenesis or progression of clear cell RCC.

Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging

PubMed Central

Ohnishi, Mutsuko; Razzaque, M. Shawkat

2010-01-01

Identifying factors that accelerate the aging process can provide important therapeutic targets for slowing down this process. Misregulation of phosphate homeostasis has been noted in various skeletal, cardiac, and renal diseases, but the exact role of phosphate toxicity in mammalian aging is not clearly defined. Phosphate is widely distributed in the body and is involved in cell signaling, energy metabolism, nucleic acid synthesis, and the maintenance of acid-base balance by urinary buffering. In this study, we used an in vivo genetic approach to determine the role of phosphate toxicity in mammalian aging. Klotho-knockout mice (klotho−/−) have a short life span and show numerous physical, biochemical, and morphological features consistent with premature aging, including kyphosis, uncoordinated movement, hypogonadism, infertility, severe skeletal muscle wasting, emphysema, and osteopenia, as well as generalized atrophy of the skin, intestine, thymus, and spleen. Molecular and biochemical analyses suggest that increased renal activity of sodium-phosphate cotransporters (NaPi2a) leads to severe hyperphosphatemia in klotho−/− mice. Genetically reducing serum phosphate levels in klotho−/− mice by generating a NaPi2a and klotho double-knockout (NaPi2a−/−/klotho−/−) strain resulted in amelioration of premature aging-like features. The NaPi2a−/−/klotho−/− double-knockout mice regained reproductive ability, recovered their body weight, reduced their organ atrophy, and suppressed ectopic calcifications, with the resulting effect being prolonged survival. More important, when hyperphosphatemia was induced in NaPi2a−/−/klotho−/− mice by feeding with a high-phosphate diet, premature aging-like features reappeared, clearly suggesting that phosphate toxicity is the main cause of premature aging in klotho−/− mice. The results of our dietary and genetic manipulation studies provide in vivo evidence for phosphate toxicity accelerating the aging process and suggest a novel role for phosphate in mammalian aging.—Ohnishi, M., Razzaque, M. S. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. PMID:20418498

Regioisomeric effects on the electronic features of indenothiophene-bridged D-π-A'-A DSSC sensitizers.

PubMed

Chou, Shu-Hua; Tsai, Chih-Hung; Wu, Chung-Chih; Kumar, Dhirendra; Wong, Ken-Tsung

2014-12-08

Two D-π-A'-A regioisomers (A-IDT-D and D-IDT-A) featuring 4,4'-di-p-tolyl-4 H-indeno[1,2-b]-thiophene as a π linker (π) between the diarylamino donor (D) and the pyrimidine-cyanoacrylic acid acceptor (A'-A) have been successfully synthesized and characterized as efficient sensitizers for the dye-sensitized solar cells (DSSCs). The different arrangements of the D and A'-A blocks on the unsymmetrical indenothiophene (IDT) core render the dipole of IDT being along (A-IDT-D) or opposite (D-IDT-A) to the direction of intramolecular (donor-to-acceptor) charge transfer, and thus induce variations in the physical properties. The experimental observations correlated well with the theoretical analyses, clearly revealing the trade-off between the molar extinction coefficient (ε) and the S0 →S1 transition energy. As a result, a superior ε value was observed for D-IDT-A, whereas a bathochromic shift in the absorption occurred in A-IDT-D. The larger ε value of D-IDT-A together with its more favorable energy level relative to TiO2 led to a higher power conversion efficiency of 7.41 % for the D-IDT-A-based DSSC, retaining approximately 95 % of the N719-based DSSC efficiency. This work manifests the clear structure-property relationship for the case of donor and acceptor components being connected by an unsymmetrical π linker and provides insights for molecular engineering of organic sensitizers. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Narrow band imaging in the diagnosis of intra-epithelial and invasive laryngeal squamous cell carcinoma: a preliminary report of two cases.

PubMed

Masaki, Takashi; Katada, Chikatoshi; Nakayama, Meijin; Takeda, Masahiko; Miyamoto, Shunsuke; Seino, Yutomo; Koizumi, Wasaburo; Tanabe, Satoshi; Horiguchi, Satoshi; Okamoto, Makito

2009-12-01

Narrow band imaging (NBI) is a novel optical technique that enhances the diagnostic capability of the gastrointestinal endoscope (GIE) by illuminating the intraepithelial papillary capillary loop (IPCL) using narrow bandwidth filters in a red-green-blue sequential illumination system (CV-260SL processor and CLV-260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan). The NBI filter sets (415 nm and 540 nm) are selected to obtain fine images of the microvascular structure. Because 415 nm is the hemoglobin absorption band, capillaries on the mucosal surface can be seen most clearly at this wavelength. NBI is able to represent more clearly both capillary patterns and the boundary between different types of tissue, which are necessary for diagnosing a tumor in its early stage (Gono K, Yamazaki K, Doguchi N, Nonami T, Obi T, Yamaguchi M, et al. Endoscopic observation of tissue by narrow band illumination. Opt Rev 2003;10:211-215, Gono K, Obi T, Yamaguchi M, Ohyama N, Machida H, Sano Y, et al. Appearance of enhanced tissue feature in narrow-band endoscopic imaging. J Biomed Opt 2004;9:568-577). We present two patients with laryngeal squamous cell carcinoma in whom the spread and the depth of invasion was evaluated with transnasal GIE equipped with NBI. Based on our results, the vascular neoplastic changes of carcinoma in situ of the larynx could be similar to carcinoma in situ of the esophagus.

77 FR 5073 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-01

... features including size, expiration date, exercise style, and certain exercise prices. FLEX option trading... cleared by The Options Clearing Corporation (``OCC'') \\17\\ and would be European style.\\18\\ Upon exercise... of the Exchange's WCOs or FCOs). \\18\\ Unlike American style options, European style options may be...

GEOCHEMICAL FEATURES OF WATER-ROCK INTERACTIONS AT THE SULPHUR BANK MERCURY MINE, LAKE COUNTY, CALIFORNIA

EPA Science Inventory

The Sulphur Bank Mercury Mine on the eastern shore of Clear Lake is the source of poor quality acid mine drainage seeping into Clear Lake. Lateral and vertical geochemical trends in ground water composition point to a number of redox reactions taking place as a function of subsu...

Are History Textbooks More "Considerate" after 20 Years?

ERIC Educational Resources Information Center

Berkeley, Sheri; King-Sears, Margaret E.; Hott, Brittany L.; Bradley-Black, Katherine

2014-01-01

Features of eighth-grade history textbooks were examined through replication of a 20-year-old study that investigated "considerateness" of textbooks. Considerate texts provide clear, coherent information and include features that promote students' comprehension, such as explicit use of organizational structures, a range of question types…

Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

PubMed Central

Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

2017-01-01

An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

Hyperchromatic laser scanning cytometry

NASA Astrophysics Data System (ADS)

Tárnok, Attila; Mittag, Anja

2007-02-01

In the emerging fields of high-content and high-throughput single cell analysis for Systems Biology and Cytomics multi- and polychromatic analysis of biological specimens has become increasingly important. Combining different technologies and staining methods polychromatic analysis (i.e. using 8 or more fluorescent colors at a time) can be pushed forward to measure anything stainable in a cell, an approach termed hyperchromatic cytometry. For cytometric cell analysis microscope based Slide Based Cytometry (SBC) technologies are ideal as, unlike flow cytometry, they are non-consumptive, i.e. the analyzed sample is fixed on the slide. Based on the feature of relocation identical cells can be subsequently reanalyzed. In this manner data on the single cell level after manipulation steps can be collected. In this overview various components for hyperchromatic cytometry are demonstrated for a SBC instrument, the Laser Scanning Cytometer (Compucyte Corp., Cambridge, MA): 1) polychromatic cytometry, 2) iterative restaining (using the same fluorochrome for restaining and subsequent reanalysis), 3) differential photobleaching (differentiating fluorochromes by their different photostability), 4) photoactivation (activating fluorescent nanoparticles or photocaged dyes), and 5) photodestruction (destruction of FRET dyes). With the intelligent combination of several of these techniques hyperchromatic cytometry allows to quantify and analyze virtually all components of relevance on the identical cell. The combination of high-throughput and high-content SBC analysis with high-resolution confocal imaging allows clear verification of phenotypically distinct subpopulations of cells with structural information. The information gained per specimen is only limited by the number of available antibodies and by sterical hindrance.

The basaloid cell is the best tissue marker for human papillomavirus in invasive penile squamous cell carcinoma: a study of 202 cases from Paraguay.

PubMed

Cubilla, Antonio L; Lloveras, Belén; Alejo, María; Clavero, Omar; Chaux, Alcides; Kasamatsu, Elena; Velazquez, Elsa F; Lezcano, Cecilia; Monfulleda, Núria; Tous, Sara; Alemany, Laia; Klaustermeier, Joellen; Muñoz, Nubia; Quint, Wim; de Sanjose, Silvia; Bosch, Francisco Xavier

2010-01-01

Human papillomavirus (HPV) has been reported in 12-82% of penile squamous cell carcinomas (SCC). There is an association of the virus with basaloid and warty carcinomas but the reported prevalence is variable. The causes of these variations are not clear. They may be owing to geographic differences, the use of different techniques to detect HPV, the status of the original paraffin blocks, or to variable criteria in tumor classification. The aims of the study were to determine the prevalence of HPV in penile SCC and subtypes using a sensitive technique, to investigate genotypes involved, and to search for other morphologic features associated with the virus from a series of cases from Paraguay. HPV detection was done by SPF-10 polymerase chain reaction followed by DNA enzyme-immunoassay and genotyping by LIPA 25 (version 1). Samples were tested at Catalan Institute of Oncology, Barcelona, and cross testing was carried out at the Delft Diagnostic Laboratories in The Netherlands. HPV was detected in 64 of 202 cases (32%). Thirteen tumors had multiple HPV genotypes. Most prevalent genotypes were HPV-16 (46 cases), HPV-6 (6 cases), and HPV-18 (4 cases), either in single or in multiple infections. HPV was preferentially associated with warty-basaloid (82%), basaloid (76%), and warty (39%) carcinomas and not detected in verrucous, mixed verrucous-papillary, pseudohyperplastic, and pseudoglandular SCCs. There was a strong association between HPV and higher histologic grade. Basaloid cells were more frequently found in HPV positive tumors (72%) and this association was statistically significant in univariate and multivariate analyses. Cells with koilocytotic features and keratinizing squamous cells were also present but to a much lesser degree (47% and 19%, respectively). In summary, HPV was found in a third of the cases and the most common genotype was HPV-16. Low-risk genotypes were rarely found in single infections, representing 4 cases among all analyzed (2%). There was an association between HPV presence and higher histologic grade and with basaloid, warty-basaloid, and warty carcinomas. Our results also suggest that, in penile SCC, the basaloid cell is the best tissue marker for oncogenic HPV infection.

Is Imprint Cytology Useful to Diagnose Malignancy for Brenner Tumors? A Case Series at a Single Institute.

PubMed

Minato, Junko; Tokunaga, Hideki; Okamoto, Satoshi; Shibuya, Yusuke; Niikura, Hitoshi; Yaegashi, Nobuo

2017-01-01

The aim of this study was to investigate cytological features of Brenner tumors according to tumor grade using imprint cytology. Between 2004 and 2015, intraoperative imprint cytology was performed on 8 patients with Brenner tumors suspected to be malignant neoplasmas on gross examination because of their large size and solid part. These consisted of 1 benign, 3 borderline, and 4 malignant tumors. In patients with benign and borderline tumors, naked nucleus-like stromal cells and tumor cells in a sheet-like arrangement were observed against a clear background. The nuclei were round to oval-shaped with finely granular chromatin patterns and small nucleoli. Papillary cell clusters and high nucleus-to-cytoplasm ratios were only observed in 1 borderline case. In cases with malignancy, the background was necrotic. The tumor cells occurred in large papillary clusters. The nuclei showed a high degree of nuclear atypia. Nuclear grooves were present in 6 of our 8 cases and they were scant in the malignant cases. Imprint cytology of Brenner tumors provided no characteristic findings to enable a definitive distinction of benign versus borderline tumors, but it enabled discrimination between malignant and other tumors. Imprint cytology can facilitate intraoperative diagnosis and aid in selecting the appropriate surgical procedure. © 2017 S. Karger AG, Basel.

Abnormal mural cell recruitment in lymphatic capillaries: a common pathological feature in chronic lymphedematous skin?

PubMed

Yu, Zi-You; Sun, Di; Luo, Yi; Liu, Ning-Fei

2016-10-01

This study aimed to explore the structural and functional characteristics of dermal lymphatic capillaries in patients with chronic LE, specifically focused on the mural cells that are associated with skin lymphatics. Forty-four patients (30 primary LE and 14 secondary LE) and eight healthy controls were enrolled in this study. Genetic analysis of the FOXC2 was performed in 18 patients with primary LE. Full-thickness skin was excised and immunohistologically stained for podoplanin and α-SMA. The proportions of α-SMA + Lv (α-SMA + Lv%) were calculated. Lymphatic vascular function was assessed by indocyanine green lymphography. Analysis of FOXC2 revealed two mutations in two patients with LDs. Histologically, thirty-nine patients exhibited increased α-SMA + mural cell coverage of lymphatic capillaries. The α-SMA + Lv% values in the superficial and deep dermis in patients with primary and secondary LE were significantly higher than in the control group. Compared with imaging findings in healthy limbs, in which the collecting lymphatics were clearly visualized, lymphedematous extremities all exhibited dermal backflow. Abnormal recruitment of mural cells in dermal lymphatic capillaries is a common pathological event in chronic LE, and may play a role in disease evolution. © 2016 John Wiley & Sons Ltd.

Cell-surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

PubMed Central

Irani, Sarosh R; Gelfand, Jeffrey M; Al-Diwani, Adam; Vincent, Angela

2014-01-01

The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface–expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface–directed antibody–mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface–directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined. PMID:24930434

Discrimination of malignant lymphomas and leukemia using Radon transform based-higher order spectra

NASA Astrophysics Data System (ADS)

Luo, Yi; Celenk, Mehmet; Bejai, Prashanth

2006-03-01

A new algorithm that can be used to automatically recognize and classify malignant lymphomas and leukemia is proposed in this paper. The algorithm utilizes the morphological watersheds to obtain boundaries of cells from cell images and isolate them from the surrounding background. The areas of cells are extracted from cell images after background subtraction. The Radon transform and higher-order spectra (HOS) analysis are utilized as an image processing tool to generate class feature vectors of different type cells and to extract testing cells' feature vectors. The testing cells' feature vectors are then compared with the known class feature vectors for a possible match by computing the Euclidean distances. The cell in question is classified as belonging to one of the existing cell classes in the least Euclidean distance sense.

Lymphovascular invasion in clear cell renal cell carcinoma--association with disease-free and cancer-specific survival.

PubMed

Belsante, Michael; Darwish, Oussama; Youssef, Ramy; Bagrodia, Aditya; Kapur, Payal; Sagalowsky, Arthur I; Lotan, Yair; Margulis, Vitaly

2014-01-01

The objective is to evaluate the effect of lymphovascular invasion (LVI) on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Patients with ccRCC who were treated surgically in 1997 to 2010 were identified. Retrospective chart review was performed to identify clinical outcomes. Independent pathologic re-review was performed by a single pathologist to confirm LVI status. Pathologic features were correlated with clinical outcomes using Kaplan-Meier and Cox regression analyses. Four hundred and nineteen patients with nonmetastatic ccRCC comprised the study cohort. Three hundred and thirty-three of these patients had an organ-confined (pT1-2, N any, and M0) disease. LVI was present in 14.3% of all nonmetastatic patients. In all patients with nonmetastatic ccRCC, presence of LVI was correlated with significantly shorter DFS (P <0.001) and CSS (P = 0.001) on Kaplan-Meier analysis. In cases of organ-confined, nonmetastatic ccRCC, presence of LVI was a significant predictor of DFS (hazard ratio = 4.0, P = 0.026) and CSS (hazard ratio = 12.7, P = 0.01) on multivariate analysis. Patients with organ-confined RCC who were LVI positive had similar DFS (P = 0.957) and CSS (P = 0.799) to patients with locally advanced tumors (pT3-pT4, N any, and M0) on Kaplan-Meier analysis. The presence of LVI is an independent predictor of both DFS and CSS in organ-confined, nonmetastatic ccRCC. LVI positivity in patients with otherwise pathologically organ-confined ccRCC confers oncologic outcomes similar to those of patients with locally advanced disease. If confirmed by others, future revisions to the tumor-node-metastasis staging system may incorporate LVI status into the prognostic algorithm of patients with RCC. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of B Cells and Humoral Immunity in Mycobacterium tuberculosis Infection

PubMed Central

Kozakiewicz, Lee; Phuah, Jiayao; Flynn, JoAnne

2014-01-01

Tuberculosis (TB) remains a serious threat to public health, causing 2 million deaths annually world-wide. The control of TB has been hindered by the requirement of long duration of treatment involving multiple chemotherapeutic agents, the increased susceptibility to Mycobacterium tuberculosis infection in the HIV-infected population, and the development of multi-drug resistant and extensively resistant strains of tubercle bacilli. An efficacious and cost-efficient way to control TB is the development of effective anti-TB vaccines. This measure requires thorough understanding of the immune response to M. tuberculosis. While the role of cell-mediated immunity in the development of protective immune response to the tubercle bacillus has been well established, the role of B cells in this process is not clearly understood. Emerging evidence suggests that B cells and humoral immunity can modulate the immune response to various intracellular pathogens, including M. tuberculosis. These lymphocytes form conspicuous aggregates in the lungs of tuberculous humans, non-human primates, and mice, which display features of germinal center B cells. In murine TB, it has been shown that B cells can regulate the level of granulomatous reaction, cytokine production, and the T cell response. This chapter discusses the potential mechanisms by which specific functions of B cells and humoral immunity can shape the immune response to intracellular pathogens in general, and to M. tuberculosis in particular. Knowledge of the B cell-mediated immune response to M. tuberculosis may lead to the design of novel strategies, including the development of effective vaccines, to better control TB. PMID:23468112

Methods on observation of fluorescence micro-imaging for microalgae

NASA Astrophysics Data System (ADS)

Ou, Lin; Zhuang, Hui-ru; Chen, Rong; Lei, Jin-pin; Liao, Xiao-hua; Lin, Wen-suo

2007-11-01

Objective: Auto-fluorescence micro-imaging of microalgae are observed by using of laser scanning confocal microscopy (LSCM) and fluorescence microscopy, so as to investigate the effect of auto fluorescence alteration on growth of irradiated microalgae irradiated, meanwhile, the method of microalgae cells stained also to be studied. Methods: Platymonas subcordiformis, Phaeodactylum tricormutum and Isochyrsis zhanjiangensis cells are stained with acridine orange, and observed by fluorescence microscopy; the three types microalgae mentioned above are irradiated by Nd:YAP laser with 10w at 1341nm, irradiating time:12s, 30s, 35s and 55s, than to be cultured 6 days, and the auto fluorescence images and fluorescence spectra of algae cells are obtained by LSCM on lambda scan mode, at excitation 488nm (Ar + laser). Results: It is showed that the shapes and the structural features of microalgae cells stained can be seen clearly, and the cytoplasm and nucleus also can be observed. The chloroplasts in cell is bigger on promoting effects, conversely, it is to be mutilated, deformation and shrink. Contrast to the CK, the peak positions of fluorescence of algae cells irradiated is similar to the whole while the peak light intensity alters. On irradiation of promoting dose, however, the auto fluorescence intensity is enhanced more than control. Conclusions: The method of cell stained can be used to observed genetic material in microalgae. There are obvious effects for laser irradiating to chloroplasts in cells, the bigger chloroplasts the greater fluorescence intensity. Physiological incentive effects of microalgae irradiated can be given expression on fluorescence characteristics and fluorescence intensity alteration of cells.

Pathological aspects of so called "hilar cholangiocarcinoma"

PubMed Central

Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

2013-01-01

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, “hilar and perihilar CC” are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed. PMID:23919110

Pathological aspects of so called "hilar cholangiocarcinoma".

PubMed

Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

2013-07-15

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, "hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

Optical characterization of lesions and identification of surgical margins in pancreatic metastasis from renal cell carcinoma by using two-photon excited fluorescence microscopy

NASA Astrophysics Data System (ADS)

Chen, Jing; Hong, Zhipeng; Chen, Hong; Chen, Youting; Xu, Yahao; Zhu, Xiaoqin; Zhuo, Shuangmu; Shi, Zheng; Chen, Jianxin

2014-11-01

Two-photon excited fluorescence (TPEF) microscopy has become a powerful instrument for imaging unstained tissue samples in biomedical research. The purpose of this study was to determine whether TPEF imaging of histological sections without hematoxylin-eosin (H-E) stain can be used to characterize lesions and identify surgical margins in pancreatic metastasis from renal cell carcinoma (RCC). The specimens of a pancreatic metastasis from RCC, as well as a primary RCC from a patient, were examined by TPEF microscopy and compared with their corresponding H-E stained histopathological results. The results showed that high-resolution TPEF imaging of unstained histological sections of pancreatic metastasis from RCC can reveal that the typical morphology of the tissue and cells in cancer tissues is different from the normal pancreas. It also clearly presented histopathological features of the collagenous capsule, which is an important boundary symbol to identify normal and cancerous tissue and to instruct surgical operation. It indicated the feasibility of using TPEF microscopy to make an optical diagnosis of lesions and identify the surgical margins in pancreatic metastasis from RCC.

Towards pH-sensitive imaging of small animals with photon-counting difference diffuse fluorescence tomography

NASA Astrophysics Data System (ADS)

Li, Jiao; Wang, Xin; Yi, Xi; Zhang, Limin; Zhou, Zhongxing; Zhao, Huijuan; Gao, Feng

2012-09-01

The importance of cellular pH has been shown clearly in the study of cell activity, pathological feature, and drug metabolism. Monitoring pH changes of living cells and imaging the regions with abnormal pH-values, in vivo, could provide invaluable physiological and pathological information for the research of the cell biology, pharmacokinetics, diagnostics, and therapeutics of certain diseases such as cancer. Naturally, pH-sensitive fluorescence imaging of bulk tissues has been attracting great attentions from the realm of near infrared diffuse fluorescence tomography (DFT). Herein, the feasibility of quantifying pH-induced fluorescence changes in turbid medium is investigated using a continuous-wave difference-DFT technique that is based on the specifically designed computed tomography-analogous photon counting system and the Born normalized difference image reconstruction scheme. We have validated the methodology using two-dimensional imaging experiments on a small-animal-sized phantom, embedding an inclusion with varying pH-values. The results show that the proposed approach can accurately localize the target with a quantitative resolution to pH-sensitive variation of the fluorescent yield, and might provide a promising alternative method of pH-sensitive fluorescence imaging in addition to the fluorescence-lifetime imaging.

Evidence for Apoplasmic Phloem Unloading in Developing Apple Fruit1

PubMed Central

Zhang, Ling-Yun; Peng, Yi-Ben; Pelleschi-Travier, Sandrine; Fan, Ying; Lu, Yan-Fen; Lu, Ying-Min; Gao, Xiu-Ping; Shen, Yuan-Yue; Delrot, Serge; Zhang, Da-Peng

2004-01-01

The phloem unloading pathway remains unclear in fleshy fruits accumulating a high level of soluble sugars. A structural investigation in apple fruit (Malus domestica Borkh. cv Golden Delicious) showed that the sieve element-companion cell complex of the sepal bundles feeding the fruit flesh is symplasmically isolated over fruit development. 14C-autoradiography indicated that the phloem of the sepal bundles was functional for unloading. Confocal laser scanning microscopy imaging of carboxyfluorescein unloading showed that the dye remained confined to the phloem strands of the sepal bundles from the basal to the apical region of the fruit. A 52-kD putative monosaccharide transporter was immunolocalized predominantly in the plasma membrane of both the sieve elements and parenchyma cells and its amount increased during fruit development. A 90-kD plasma membrane H+-ATPase was also localized in the plasma membrane of the sieve element-companion cell complex. Studies of [14C]sorbitol unloading suggested that an energy-driven monosaccharide transporter may be functional in phloem unloading. These data provide clear evidence for an apoplasmic phloem unloading pathway in apple fruit and give information on the structural and molecular features involved in this process. PMID:15122035

Relevant Features of a Triethylene Glycol Dimethyl Ether-Based Electrolyte for Application in Lithium Battery.

PubMed

Carbone, Lorenzo; Di Lecce, Daniele; Gobet, Mallory; Munoz, Stephen; Devany, Matthew; Greenbaum, Steve; Hassoun, Jusef

2017-05-24

Triethylene glycol dimethyl ether (TREGDME) dissolving lithium trifluoromethanesulfonate (LiCF 3 SO 3 ) is studied as a suitable electrolyte medium for lithium battery. Thermal and rheological characteristics, transport properties of the dissolved species, and the electrochemical behavior in lithium cell represent the most relevant investigated properties of the new electrolyte. The self-diffusion coefficients, the lithium transference numbers, the ionic conductivity, and the ion association degree of the solution are determined by pulse field gradient nuclear magnetic resonance and electrochemical impedance spectroscopy. The study sheds light on the determinant role of the lithium nitrate (LiNO 3 ) addition for allowing cell operation by improving the electrode/electrolyte interfaces and widening the voltage stability window. Accordingly, an electrochemical activation procedure of the Li/LiFePO 4 cell using the upgraded electrolyte leads to the formation of stable interfaces at the electrodes surface as clearly evidenced by cyclic voltammetry, impedance spectroscopy, and ex situ scanning electron microscopy. Therefore, the lithium battery employing the TREGDME-LiCF 3 SO 3 -LiNO 3 solution shows a stable galvanostatic cycling, a high efficiency, and a notable rate capability upon the electrochemical conditions adopted herein.

CD147 regulates cancer migration via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling.

PubMed

Cui, Hong-Yong; Wang, Shi-Jie; Miao, Ji-Yu; Fu, Zhi-Guang; Feng, Fei; Wu, Jiao; Yang, Xiang-Min; Chen, Zhi-Nan; Jiang, Jian-Li

2016-02-02

The acquisition of inappropriate migratory feature is crucial for tumor metastasis. It has been suggested that CD147 and Annexin A2 are involved in regulating tumor cell movement, while the regulatory mechanisms are far from clear. In this study, we demonstrated that CD147 physically interacted with the N-terminal domain of Annexin A2 and decreased Annexin A2 phosphorylation on tyrosine 23. In vitro kinase assay showed that the I domain of CD147 was indispensable for CD147-mediated downregulation of Annexin A2 phosphorylation by Src. Furthermore, we determined that p-Annexin A2 promoted the expression of dedicator of cytokinesis 3 (DOCK3) and DOCK3 blocked β-catenin nuclear translocation, resulting in inhibition of β-catenin signaling. In addition, DOCK3 inhibited lamellipodium dynamics and tumor cell movement. Also, we found that β-catenin signaling increased WAVE2 expression. Therefore, DOCK3 was characterized as a negative regulator of WAVE2 expression via inhibiting β-catenin signaling. Our study provides the first evidence that CD147 promotes tumor cell movement and metastasis via direct interaction with Annexin A2 and DOCK3-β-catenin-WAVE2 signaling axis.

Pagetoid spread of bladder urothelial carcinoma to the vagina and vulva.

PubMed

Lu, Bingjian; Liang, Yun

2015-01-01

To study the clinicopathologic features of a rare disease of pagetoid urothelial intraepithelial neoplasia (PUIN) in the vulva. We reviewed a case of PUIN in a Chinese woman with a long history of bladder urothelial carcinoma. The patient presented with vulvar pruritus for more than 1 month. Gynecologic examination showed a red, thickened, eczematoid lesion in the bilateral labia minora and a palpable 4-cm mass between the middle part of the vagina and the urethral meatus. Microscopically, the neoplastic cells with clear or pale eosinophilic cytoplasm were distributed throughout the squamous epithelium, with a predilection for the middle and basal portion in the vulva. Acantholysis-related papillary formation and pagetoid spread pattern to the normal squamous epithelium were also present. Invasive carcinoma was found underneath the unremarkable squamous epithelium in the vaginal biopsy. Immunohistochemistry demonstrated that these cells were negative for mucin stain, carcinoembryonic antigen, and 34βE12 and were strongly positive for cytokeratins 5/6, 7, 18, 19, and 20. This rare entity of PUIN was associated with metastatic urothelial carcinoma and should be discriminated from vulvar Paget disease and pagetoid squamous cell carcinoma in situ.

Cediranib Maleate and Olaparib or Standard Chemotherapy in Treating Patients With Recurrent Platinum-Resistant or -Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-06-15

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2017-05-02

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

TEN MASTER TEACHER AND PROGRAM AWARD PROGRAMS.

ERIC Educational Resources Information Center

KOVACH, EDITH M.A.

IN 1966 THE AMERICAN CLASSICAL LEAGUE HONORED THREE TEACHERS WITH ITS MASTER SECONDARY SCHOOL LATIN TEACHER AND PROGRAM AWARD. AMONG THE 32 PROGRAMS CITED FOR RECOGNITION, TEN (INCLUDING THOSE OF THE AWARD WINNERS) POSSESS CLEARLY INNOVATIVE FEATURES. IN BRIEF THEY FEATURE (1) A FIFTH YEAR ADVANCED PLACEMENT PROGRAM, LATIN AS INTRODUCTORY TO…

Critical Aesthetic Realism

ERIC Educational Resources Information Center

McMahon, Jennifer A.

2011-01-01

A clear-cut concept of the aesthetic is elusive. Kant's "Critique of Judgment" presents one of the more comprehensive aesthetic theories from which one can extract a set of features, some of which pertain to aesthetic experience and others to the logical structure of aesthetic judgment. When considered together, however, these features present a…

CDKL5, a novel MYCN-repressed gene, blocks cell cycle and promotes differentiation of neuronal cells.

PubMed

Valli, Emanuele; Trazzi, Stefania; Fuchs, Claudia; Erriquez, Daniela; Bartesaghi, Renata; Perini, Giovanni; Ciani, Elisabetta

2012-01-01

Mutations in the CDKL5 (cyclin-dependent kinase-like 5) gene are associated with a severe epileptic encephalopathy (early infantile epileptic encephalopathy type 2, EIEE2) characterized by early-onset intractable seizures, infantile spasms, severe developmental delay, intellectual disability, and Rett syndrome (RTT)-like features. Despite the clear involvement of CDKL5 mutations in intellectual disability, the function of this protein during brain development and the molecular mechanisms involved in its regulation are still unknown. Using human neuroblastoma cells as a model system we found that an increase in CDKL5 expression caused an arrest of the cell cycle in the G(0)/G(1) phases and induced cellular differentiation. Interestingly, CDKL5 expression was inhibited by MYCN, a transcription factor that promotes cell proliferation during brain development and plays a relevant role in neuroblastoma biology. Through a combination of different and complementary molecular and cellular approaches we could show that MYCN acts as a direct repressor of the CDKL5 promoter. Overall our findings unveil a functional axis between MYCN and CDKL5 governing both neuron proliferation rate and differentiation. The fact that CDKL5 is involved in the control of both neuron proliferation and differentiation may help understand the early appearance of neurological symptoms in patients with mutations in CDKL5. Copyright © 2012 Elsevier B.V. All rights reserved.

Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors.

PubMed

Boidot, Romain; Végran, Frédérique; Meulle, Aline; Le Breton, Aude; Dessy, Chantal; Sonveaux, Pierre; Lizard-Nacol, Sarab; Feron, Olivier

2012-02-15

The monocarboxylate transporter (MCT) family member MCT1 can transport lactate into and out of tumor cells. Whereas most oxidative cancer cells import lactate through MCT1 to fuel mitochondrial respiration, the role of MCT1 in glycolysis-derived lactate efflux remains less clear. In this study, we identified a direct link between p53 function and MCT1 expression. Under hypoxic conditions, p53 loss promoted MCT1 expression and lactate export produced by elevated glycolytic flux, both in vitro and in vivo. p53 interacted directly with the MCT1 gene promoter and altered MCT1 mRNA stabilization. In hypoxic p53(-/-) tumor cells, NF-κB further supported expression of MCT1 to elevate its levels. Following glucose deprivation, upregulated MCT1 in p53(-/-) cells promoted lactate import and favored cell proliferation by fuelling mitochondrial respiration. We also found that MCT1 expression was increased in human breast tumors harboring p53 mutations and coincident features of hypoxia, with higher MCT1 levels associated with poorer clinical outcomes. Together, our findings identify MCT1 as a target for p53 repression and they suggest that MCT1 elevation in p53-deficient tumors allows them to adapt to metabolic needs by facilitating lactate export or import depending on the glucose availability.

Spastin-Interacting Protein NA14/SSNA1 Functions in Cytokinesis and Axon Development

PubMed Central

Chang, Jaerak; Blackstone, Craig

2014-01-01

Hereditary spastic paraplegias (HSPs) are a genetically diverse group of inherited neurological disorders (SPG1-72) with the cardinal feature of prominent lower-extremity spasticity due to a length-dependent axonopathy of corticospinal motor neurons. The most frequent form of autosomal dominant HSP results from mutations of the SPG4 gene product spastin. This is an ATPase associated with diverse cellular activities (AAA) protein that binds to and severs microtubules. While spastin participates in crucial cellular processes such as cytokinesis, endosomal tubulation, and axon development, its role in HSP pathogenesis remains unclear. Spastin interacts in cells with the NA14 protein, a major target for auto-antibodies in Sjögren's syndrome (nuclear autoantigen 1; SSNA1). Our analysis of endogenous spastin and NA14 proteins in HeLa cells and rat cortical neurons in primary culture revealed a clear distribution of both proteins to centrosomes, with NA14 localizing specifically to centrioles. Stable NA14 knockdown in cell lines dramatically affected cell division, in particular cytokinesis. Furthermore, overexpression of NA14 in neurons significantly increased axon outgrowth and branching, while also enhancing neuronal differentiation. We postulate that NA14 may act as an adaptor protein regulating spastin localization to centrosomes, temporally and spatially regulating the microtubule-severing activity of spastin that is particularly critical during the cell cycle and neuronal development. PMID:25390646

Clinicopathological importance of Papanicolaou smears for the diagnosis of premalignant and malignant lesions of the cervix.

PubMed

Bukhari, Mulazim Hussain; Saba, Kanwal; Qamar, Samina; Majeed, Muhammad Muddasar; Niazi, Shahida; Naeem, Samina

2012-01-01

Premalignant and malignant lesions are not uncommon in Pakistani women, especially in the older age-groups This study was conducted to determine the clinicopathological importance of conventional Papanicolaou (Pap) smears for the diagnosis of premalignant and malignant lesions of the cervix. Pap smears of 1000 women were examined from January 2007 to June 2009. Only cases with neoplastic cytology were included. The overall frequency of normal, inadequate, neoplastic, and infective smears was 50%, 1.8%, 10.2%, and 38.3%, respectively. Most of the patients (67%) were in the postmenopausal age-group, with the mean age being 44.7±15.63 years. The commonest clinical signs/symptoms seen among the 102 patients with neoplastic gynecological lesions were vaginal discharge and abnormal bleeding (93/102;(91.2% and 62/102;60.7%). Of the 102 cases with neoplastic lesions 46 patients (45%) had low-grade squamous cell intraepithelial lesions (LSILs), 22 (21.5%) had high-grade squamous cell intraepithelial lesions (HSILs), 14 (13.7%) had squamous cell carcinoma, and 6 (5.8%) showed features of adenocarcinoma. Ten (9.8%) cases showed cytology of atypical squamous cells of undetermined significance (ASCUS) and four (3.9%) cases had atypical glandular cells of undetermined significance (AGUS). We conclude that cervical smear examination is well suited for diagnosing neoplastic disease. It is clear that cervical neoplastic lesions are becoming a problem in Pakistan.

Unusual presentation of Warthin variant of Papillary thyroid carcinoma with lymph nodal metastases in a patient of Graves' disease.

PubMed

Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Arun, B R

2015-01-01

Warthin-like Papillary thyroid carcinoma (WPTC) is a rare variant of papillary carcinoma of thyroid, PTC which derives its name by closely resembling Warthin's tumor of salivary gland. Hallmark histological feature of this variant is papillary folding lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. It is thought to be one of those differentiated thyroid cancers with favorable prognosis. We report a case of Graves' disease with a cold nodule harboring WPTC with initial presentation of lymph nodal metastases. It is important to identify this peculiar variant of PTC as 5 to 10% of them undergo dedifferentiation and 30% have the lymph nodal metastases and extra thyroidal extension.

Commerical (terrestrial) and modified solar array design studies for low cost, low power space applications

NASA Technical Reports Server (NTRS)

Kolecki, J. C.; Riley, T. J.

1980-01-01

The suitability of commercial (terrestrial) solar arrays for use in low Earth orbit is examined. It is shown that commercial solar arrays degrade under thermal cycling because of material flexure, and that certain types of silicones used in the construction of these arrays outgas severely. Based on the results, modifications were made. The modified array retains the essential features of typical commercial arrays and can be easily built by commercial fabrication techniques at low cost. The modified array uses a metal tray for containment, but eliminates the high outgassing potting materials and glass cover sheets. Cells are individually mounted with an adhesive and individually covered with glass cover slips, or clear plastic tape. The modified array is found to withstand severe thermal cycling for long intervals of time.

Feature Extraction Assessment Study.

DTIC Science & Technology

1984-11-01

base in the form of orthophotos , control manuscripts, . or maps or charts; aids to feature identification such as im- agery (rectified and unrectified...manually delineated (i.e. , drawn by * hand) on a feature manuscript which may be a mylar overlay on an orthophoto or other control base. Once delineated...partition of tiled constant gray level regions, with addi- tive noise in each, it is not clear that any segmentation tech- nique would identify each

Origins of Sinuous and Braided Channels on Ascraeus Mons, Mars - A Keck Geology Consortium Undergraduate Research Project

NASA Technical Reports Server (NTRS)

de Wet, A. P.; Bleacher, J. E.; Garry, W. B.

2012-01-01

Water has clearly played an important part in the geological evolution of Mars. There are many features on Mars that were almost certainly formed by fluvial processes -- for example, the channels Kasei Valles and Ares Vallis in the Chryse Planitia area of Mars are almost certainly fluvial features. On the other hand, there are many channel features that are much more difficult to interpret -- and have been variously attributed to volcanic and fluvial processes. Clearly unraveling the details of the role of water on Mars is extremely important, especially in the context of the search of extinct or extant life. In this project we built on our recent work in determining the origin of one channel on the southwest rift apron of Ascraeus Mons. This project, funded by the Keck Geology Consortium and involving 4 undergraduate geology majors took advantage of the recently available datasets to map and analyze similar features on Ascraeus Mons and some other areas of Mars. A clearer understanding of how these particular channel features formed might lead to the development of better criteria to distinguish how other Martian channel features formed. Ultimately this might provide us with a better understanding of the role of volcanic and fluvial processes in the geological evolution of Mars.

Evaluating the safety risk of roadside features for rural two-lane roads using reliability analysis.

PubMed

Jalayer, Mohammad; Zhou, Huaguo

2016-08-01

The severity of roadway departure crashes mainly depends on the roadside features, including the sideslope, fixed-object density, offset from fixed objects, and shoulder width. Common engineering countermeasures to improve roadside safety include: cross section improvements, hazard removal or modification, and delineation. It is not always feasible to maintain an object-free and smooth roadside clear zone as recommended in design guidelines. Currently, clear zone width and sideslope are used to determine roadside hazard ratings (RHRs) to quantify the roadside safety of rural two-lane roadways on a seven-point pictorial scale. Since these two variables are continuous and can be treated as random, probabilistic analysis can be applied as an alternative method to address existing uncertainties. Specifically, using reliability analysis, it is possible to quantify roadside safety levels by treating the clear zone width and sideslope as two continuous, rather than discrete, variables. The objective of this manuscript is to present a new approach for defining the reliability index for measuring roadside safety on rural two-lane roads. To evaluate the proposed approach, we gathered five years (2009-2013) of Illinois run-off-road (ROR) crash data and identified the roadside features (i.e., clear zone widths and sideslopes) of 4500 300ft roadway segments. Based on the obtained results, we confirm that reliability indices can serve as indicators to gauge safety levels, such that the greater the reliability index value, the lower the ROR crash rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metastatic clear cell eccrine hidradenocarcinoma of the vulva: survival after primary surgical resection.

PubMed

Massad, L S; Bitterman, P; Clarke-Pearson, D L

1996-05-01

A case of clear cell eccrine hidradenocarcinoma of the vulva metastatic to regional lymph nodes with long survival after surgical resection is presented. Like the only other case reported to date, this suggests that surgical therapy alone may be adequate, even when metastasis is present.

Metastatic clear-cell hidradenocarcinoma of the vulva.

PubMed

Messing, M J; Richardson, M S; Smith, M T; King, L; Gallup, D G

1993-02-01

Clear-cell hidradenocarcinoma is a malignant tumor of sweat gland origin. It is most often found on the trunk, head, and extremities. This case report describes a rare occurrence of this tumor on the vulva of a young woman. The discovery of metastatic disease reflects the potentially aggressive nature of this tumor.

Targeting HIF2 in Clear Cell Renal Cell Carcinoma.

PubMed

Cho, Hyejin; Kaelin, William G

2016-01-01

Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1. These compounds inhibit clear cell renal cell carcinoma growth in preclinical models, and PT2385 has now entered the clinic. Nonetheless, the availability of such compounds, together with clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing approaches, has revealed a previously unappreciated heterogeneity among clear cell renal carcinomas and patient-derived xenografts with respect to HIF2 dependence, suggesting that predictive biomarkers will be needed to optimize the use of such agents in the clinic. © 2016 Cho and Kaelin; Published by Cold Spring Harbor Laboratory Press.

Mueller matrix polarimetry for characterizing microstructural variation of nude mouse skin during tissue optical clearing.

PubMed

Chen, Dongsheng; Zeng, Nan; Xie, Qiaolin; He, Honghui; Tuchin, Valery V; Ma, Hui

2017-08-01

We investigate the polarization features corresponding to changes in the microstructure of nude mouse skin during immersion in a glycerol solution. By comparing the Mueller matrix imaging experiments and Monte Carlo simulations, we examine in detail how the Mueller matrix elements vary with the immersion time. The results indicate that the polarization features represented by Mueller matrix elements m22&m33&m44 and the absolute values of m34&m43 are sensitive to the immersion time. To gain a deeper insight on how the microstructures of the skin vary during the tissue optical clearing (TOC), we set up a sphere-cylinder birefringence model (SCBM) of the skin and carry on simulations corresponding to different TOC mechanisms. The good agreement between the experimental and simulated results confirm that Mueller matrix imaging combined with Monte Carlo simulation is potentially a powerful tool for revealing microscopic features of biological tissues.