Hidradenocarcinomas: A Brief Review and Future Directions

2010 ◽  
Vol 134 (5) ◽  
pp. 781-785 ◽  
Author(s):  
Steven Gauerke ◽  
James J. Driscoll
Keyword(s):  
Clear Cell ◽  
De Novo ◽  
Regional Lymph Nodes ◽  
Future Directions ◽  
Future Studies ◽  
Molecular Events ◽  
Variable Morphology ◽  
Metastatic Sites ◽  
Multiple Recurrences ◽  
Adnexal Tumors

Abstract Hidradenocarcinomas are rare, aggressive skin adnexal tumors of sweat gland origin that demonstrate a high potential for local recurrence, metastasis, and poor outcome. These neoplasms can derive from preexisting clear cell hidradenomas but more commonly appear de novo, with the molecular events responsible for the pathogenesis currently unknown. Historically, diagnosis has been difficult because of the few cases, inconsistent nomenclature, variable morphology of cells that compose the neoplasm, and confusion with other visceral metastatic tumors. Presentation is generally benign with an indolent clinical course that typically includes local and multiple recurrences. Despite wide-excision surgery, disease at regional lymph nodes and metastatic sites is common and linked to decreased survival. Currently, molecular markers of pathogenesis as well as effective forms of adjuvant chemotherapy are lacking. Future studies are required to identify the histopathologic and immunohistochemical features, which may facilitate diagnosis and foster development of molecularly targeted forms of adjuvant therapy.

scholarly journals MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Brian Shuch ◽  
Ryan Falbo ◽  
Fabio Parisi ◽  
Adebowale Adeniran ◽  
Yuval Kluger ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarkers ◽  
Cell Renal Cell Carcinoma ◽  
Primary Tumors ◽  
Distant Tissue ◽  
Significant Expression ◽  
Metastatic Sites

Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available.Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1). MET expression weakly correlated between primary and matched metastatic sites (R=0.5) and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39).Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

scholarly journals Protein synthesis persists during necrotic cell death

2005 ◽  
Vol 168 (4) ◽  
pp. 545-551 ◽  
Author(s):  
Xavier Saelens ◽  
Nele Festjens ◽  
Eef Parthoens ◽  
Isabel Vanoverberghe ◽  
Michael Kalai ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
De Novo ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Necrotic Cell Death ◽  
Necrotic Cell ◽  
Proteolytic Activation ◽  
Double Stranded Rna ◽  
Molecular Events

Cell death is an intrinsic part of metazoan development and mammalian immune regulation. Whereas the molecular events orchestrating apoptosis have been characterized extensively, little is known about the biochemistry of necrotic cell death. Here, we show that, in contrast to apoptosis, the induction of necrosis does not lead to the shut down of protein synthesis. The rapid drop in protein synthesis observed in apoptosis correlates with caspase-dependent breakdown of eukaryotic translation initiation factor (eIF) 4G, activation of the double-stranded RNA-activated protein kinase PKR, and phosphorylation of its substrate eIF2-α. In necrosis induced by tumor necrosis factor, double-stranded RNA, or viral infection, de novo protein synthesis persists and 28S ribosomal RNA fragmentation, eIF2-α phosphorylation, and proteolytic activation of PKR are absent. Collectively, these results show that, in contrast to apoptotic cells, necrotic dying cells retain the opportunity to synthesize proteins.

Clear Cell Sarcoma of Tendons and Aponeuroses: A Review

2007 ◽  
Vol 131 (1) ◽  
pp. 152-156 ◽  
Author(s):  
Daniel C. Dim ◽  
Linda D. Cooley ◽  
Roberto N. Miranda
Keyword(s):  
Clear Cell ◽  
Current Knowledge ◽  
S100 Protein ◽  
Clear Cell Sarcoma ◽  
Prognostic Indicators ◽  
Gene Transcript ◽  
Poor Overall Survival ◽  
Regional Lymph Nodes ◽  
Cell Sarcoma ◽  
Eosinophilic Cytoplasm

Abstract Clear cell sarcoma of tendons and aponeuroses, also referred to as malignant melanoma of soft parts, is a rare malignancy derived from neural crest cells. It usually presents in the distal lower extremities of young adults, frequently attached to tendons or aponeuroses. It behaves like a high-grade soft tissue sarcoma and is associated with poor overall survival. Magnetic resonance imaging studies of the lesion reveal T1 hypointensity, T2 hyperintensity, and gadolinium uptake. Grossly, the tumor is usually circumscribed with a histologic pattern of uniform polygonal to fusiform cells with clear to pale eosinophilic cytoplasm divided into variably sized clusters by fibrous septa. Immunohistochemical studies in most cases show that the neoplastic cells are positive with HMB-45 and react with antibody against S100 protein. Most cases show a reciprocal cytogenetic translocation t(12;22)(q13;q12) that creates a unique chimeric fusion EWSR1/ATF1 gene transcript. Metastasis occurs mainly to regional lymph nodes and lungs. Poor prognostic indicators include a tumor size equal to or more than 5 cm, presence of metastasis, and necrosis. The mainstay of treatment is wide excision of the tumor. The use of sentinel lymph node biopsy may become an important procedure in detecting occult regional metastasis and guiding the extent of surgery. The beneficial effects of adjuvant chemotherapy and radiotherapy have not been fully evaluated. This article provides a short overview of the current knowledge of clear cell sarcoma of tendons and aponeuroses.

scholarly journals Canine Cutaneous Clear Cell Adnexal Carcinoma: Histopathology, Immunohistochemistry, and Biologic Behavior of 26 Cases

2005 ◽  
Vol 17 (5) ◽  
pp. 403-411 ◽  
Author(s):  
F. Y. Schulman ◽  
T. P. Lipscomb ◽  
T. J. Atkin
Keyword(s):  
Clear Cell ◽  
Regional Lymph Node ◽  
Smooth Muscle Actin ◽  
Periodic Acid ◽  
Dermal Papilla ◽  
Low Grade ◽  
Periodic Acid Schiff ◽  
Regional Lymph Nodes ◽  
S 100 ◽  
Clear Cytoplasm

Thirty tumors including 27 distinctive cutaneous neoplasms and 3 metastatic tumors from 26 dogs were collected from diagnostic submissions to 3 laboratories. Characteristic histopathologic features included location in the subcutis or dermis (or both); lobular, nodular, and nest-like architecture; and a component of epithelioid cells with clear cytoplasm. Additional features present in most cases included follicular dermal papilla-like structures, low mitotic index, nuclear pleomorphism, necrosis, and mineralization. Cytoplasmic periodic acid Schiff—positivity, which was abolished by pretreatment with diastase, indicated the presence of glycogen in all cases. The oil red O stain did not demonstrate cytoplasmic lipid. Melanin granules, accentuated by the Fontana-Masson method, were observed infrequently. A sparsely cellular mucinous stroma and stromal cartilaginous differentiation were uncommon. By immunohistochemistry, neoplastic cells stained positively for cytokeratin (29 of 29), vimentin (28 of 28), S-100 protein (24 of 29), and melan A (8 of 12); results were negative for smooth muscle actin and calponin in all cases. Clinical follow-up information was obtained on all 26 dogs. One tumor recurred, 1 metastasized to a regional lymph node, and 1 metastasized to regional lymph nodes twice. In another case, possible pulmonary metastasis was noted radiographically. The findings are consistent with a poorly differentiated, low-grade, adnexal carcinoma of the skin. Similar canine cutaneous neoplasms have been reported as “clear-cell hidradenocarcinoma” and “follicular stem cell carcinoma.” The authors propose the designation “cutaneous clear cell adnexal carcinoma.”

Directed evolution approaches for optogenetic tool development

2021 ◽  
Author(s):  
Jaewan Jang ◽  
G. Andrew Woolley
Keyword(s):  
Directed Evolution ◽  
Recent Progress ◽  
Tool Development ◽  
Future Directions ◽  
Molecular Events

Photoswitchable proteins enable specific molecular events occurring in complex biological settings to be probed in a rapid and reversible fashion. Recent progress in the development of photoswitchable proteins as components of optogenetic tools has been greatly facilitated by directed evolution approaches in vitro, in bacteria, or in yeast. We review these developments and suggest future directions for this rapidly advancing field.

Metastatic Patterns of Cancers: Results From a Large Autopsy Study

2008 ◽  
Vol 132 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Guy diSibio ◽  
Samuel W. French
Keyword(s):  
Quantitative Description ◽  
Primary Cancer ◽  
Autopsy Study ◽  
Regional Lymph Nodes ◽  
Design Review ◽  
Medical Centers ◽  
Metastatic Patterns ◽  
Quantitative Analyses ◽  
Metastatic Sites ◽  
Do So

Abstract Context.—Many studies have addressed metastatic patterns seen among various cancers. No recent studies, however, provide quantitative analyses of such patterns arising from a broad range of cancers based primarily on postmortem tissue analyses. Objective.—To provide a quantitative description of metastatic patterns among different primary cancers based on data obtained from a large, focused autopsy study. Design.—Review of data from 3827 autopsies, performed between 1914 and 1943 on patients from 5 affiliated medical centers, comprising 41 different primary cancers and 30 different metastatic sites. Results.—Testicular cancers were most likely to metastasize (5.8 metastases per primary cancer), whereas duodenal cancers were least likely to do so (0.6 metastases per primary cancer). Preferred metastatic sites varied among the primary cancers analyzed. Overall, regional lymph nodes were the most common metastatic target (20.6% of total), whereas testes were the least common (0.1% of total). Conclusions.—Not surprisingly, different primary cancers tended to metastasize, with differing frequencies, to different sites. These varying metastatic patterns might be helpful in deducing the origins of cancers whose primary sites are unclear at presentation.

Knowledge-intensive entrepreneurship: a systematic review and future directions

2019 ◽  
Vol 17 (1) ◽  
pp. 50-67
Author(s):  
Caio Sousa ◽  
Luciana Soares Silva
Keyword(s):  
Systematic Review ◽  
Systematic Approach ◽  
Future Directions ◽  
Content Type ◽  
Future Studies ◽  
Knowledge Intensive ◽  
Relationship Of ◽  
The Relationship ◽  
Knowledge Intensive Entrepreneurship ◽  
Focal Issue

Purpose This study aims to propose a framework based on the main theoretical and empirical contributions present in the literature and articulate the main paths for future studies in knowledge-intensive entrepreneurship (KIE). Design/methodology/approach Using the systematic review method from a survey of 85 articles, related to the KIE focal issue, originated from the Web of Science, it was possible to exhaustively analyze the studies and to divide the theme into key categories. Findings The present research has raised the relationship of five categories to KIE conceptualizations; the data suggest that although the literature indicates a distancing from KIE research, there are multidisciplinary themes and approaches interlinked in the studies. Originality/value The systematic approach in the main theoretical and empirical contributions in KIE enabled us to relate five categories (entrepreneurs, innovation, internationalization, location and triple alliance), and finally, to understand the gaps suggested by the researchers.

scholarly journals Personality and Incident Alzheimer’s Disease: Theory, Evidence, and Future Directions

2018 ◽  
Vol 75 (3) ◽  
pp. 513-521 ◽  
Author(s):  
Suzanne C Segerstrom
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Health Behavior ◽  
Personality Change ◽  
Present Review ◽  
Future Directions ◽  
Common Cause ◽  
Future Studies ◽  
Disease Spectrum ◽  
Noninvasive Assessment

Abstract Personality, especially the dimensions of neuroticism and conscientiousness, has prospectively predicted the risk of incident Alzheimer’s disease (AD). Such a relationship could be explained by personality and AD risk having a common cause such as a gene; by personality creating a predisposition for AD through health behavior or inflammation; by personality exerting a pathoplastic effect on the cognitive consequences of neuropathology; or by AD and personality change existing on a disease spectrum that begins up to decades before diagnosis. Using the 5-dimensional taxonomy of personality, the present review describes how these models might arise, the evidence for each, and how they might be distinguished from one another empirically. At present, the evidence is sparse but tends to suggest predisposition and/or pathoplastic relationships. Future studies using noninvasive assessment of neuropathology are needed to distinguish these 2 possibilities.

Abstract 1493: Specific miRNA signatures characterize different metastatic sites in clear cell renal cell carcinoma

2014 ◽  
Author(s):  
Joana Heinzelmann ◽  
Franzsika Stolzenbach ◽  
Robert Schneeweiss ◽  
Ulrike Wickmann ◽  
Sophie Baumgart ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Sites

scholarly journals HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species

2019 ◽  
Vol 12 (601) ◽  
pp. eaay0482 ◽  
Author(s):  
Hilary E. Nicholson ◽  
Zeshan Tariq ◽  
Benjamin E. Housden ◽  
Rebecca B. Jennings ◽  
Laura A. Stransky ◽  
...  
Keyword(s):  
Clear Cell ◽  
De Novo ◽  
Synthetic Lethality ◽  
Acquired Resistance ◽  
Hypoxia Inducible Factor ◽  
Suppressor Gene ◽  
Cell Renal Cell Carcinoma ◽  
Antiproliferative Effects ◽  
Cyclin Dependent Kinases ◽  
Ccrcc Cell

Inactivation of the VHL tumor suppressor gene is the signature initiating event in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, and causes the accumulation of hypoxia-inducible factor 2α (HIF-2α). HIF-2α inhibitors are effective in some ccRCC cases, but both de novo and acquired resistance have been observed in the laboratory and in the clinic. Here, we identified synthetic lethality between decreased activity of cyclin-dependent kinases 4 and 6 (CDK4/6) and VHL inactivation in two species (human and Drosophila) and across diverse human ccRCC cell lines in culture and xenografts. Although HIF-2α transcriptionally induced the CDK4/6 partner cyclin D1, HIF-2α was not required for the increased CDK4/6 requirement of VHL−/− ccRCC cells. Accordingly, the antiproliferative effects of CDK4/6 inhibition were synergistic with HIF-2α inhibition in HIF-2α–dependent VHL−/− ccRCC cells and not antagonistic with HIF-2α inhibition in HIF-2α–independent cells. These findings support testing CDK4/6 inhibitors as treatments for ccRCC, alone and in combination with HIF-2α inhibitors.

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