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1,111 results on '"Siegal, Gene P."'

203. The RANK Pathway in Advanced Breast Cancer

Author

Li, Rong, primary, Zhang, Kui, additional, Penedo, Thuy Linh, additional, Kragel, Christopher P., additional, Grizzle, William E., additional, Hameed, Omar, additional, Siegal, Gene P., additional, and Wei, Shi, additional

Published
2016
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209. Malignant Ewing-Like Neoplasm With an EWSR1-KLF15 Fusion: At the Crossroads of a Myoepithelial Carcinoma and a Ewing-Like Sarcoma. A Case Report With Treatment Options.

Author

Stevens, Todd M., Qarmali, Morad, Morlote, Diana, Mikhail, Fady M., Swensen, Jeffrey, Gatalica, Zoran, Siegal, Gene P., and Conry, Robert M.

Subjects
GENE fusion, METASTASIS, DIAGNOSTIC immunohistochemistry, CYTOGENETICS, IFOSFAMIDE, ETOPOSIDE
Abstract

We present a case of a malignant Ewing-like neoplasm of the parotid gland in a 20-year-old woman with an EWSR1-KLF15 gene fusion that presented with pulmonary metastasis. Despite the fact that the tumor was essentially immunohistochemically negative for keratins, p63, and p40, we interpret this neoplasm as an unusual form of a highgrade myoepithelial carcinoma based on its focal plasmacytoid cytology, chondromyxoid matrix, SOX10, S100 protein, and calponin expression, and the knowledge that the EWSR1-KLF15 gene fusion has, to date, only been identified in 2 tumors, both myoepithelial carcinomas of the kidney. We also present a cytogenetic analysis of this unusual tumor. This "Ewing-like myoepithelial carcinoma" initially did not respond to 2 cycles of ifosfamide and etoposide alternated with a cycle of cytoxan, adriamycin, and vincristine, a standard regimen for Ewing sarcoma. Subsequent oral pazopanib therapy did result in a reduction of the patient's pulmonary and nodal disease. [ABSTRACT FROM AUTHOR]

Published
2018
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212. A Phase I Study of a Tropism Modified Conditionally Replicative Adenovirus (CRAd) for Recurrent Gynecologic Malignancies

Author

Kimball, Kristopher J., Preuss, Meredith A., Barnes, Mack N., Wang, Minghui, Siegal, Gene P., Wan, Wen, Kuo, Huichien, Saddekni, Souheil, Stockard, Cecil R., Grizzle, William E., Harris, Raymond D., Aurigemma, Rosemarie, Curiel, David T., and Alvarez, Ronald D.

Subjects
Aged, 80 and over, Oncolytic Virotherapy, Organisms, Genetically Modified, Genital Neoplasms, Female, Carcinoma, Middle Aged, Virus Replication, Cancer Vaccines, Article, Adenoviridae, Viral Tropism, Recurrence, Tumor Cells, Cultured, Vaccines, DNA, Humans, Female, Oligopeptides, Aged
Abstract

To determine the maximum tolerated dose (MTD), toxicity spectrum, clinical activity, and biological effects of the tropism-modified, infectivity-enhanced conditionally replicative adenovirus (CRAd), Ad5-Δ24-Arg-Gly-Asp (RGD), in patients with malignant gynecologic diseases.Cohorts of eligible patients were treated daily for 3 days through an i.p. catheter. Vector doses ranged from 1 × 10(9) to 1 × 10(12) viral particles per day. Toxicity was evaluated using CTCv3.0. CA-125 and Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to determine clinical efficacy. Corollary biological studies included assessment of CRAd replication, wild-type virus generation, viral shedding, and neutralizing antibody response.Twenty-one patients were treated. Adverse clinical effects were limited to grade 1/2 fever, fatigue, or abdominal pain. No vector-related grade 3/4 toxicities were noted. No clinically significant laboratory abnormalities were noted. The maximum tolerated dose was not reached. Over a 1 month follow-up, 15 (71%) patients had stable disease and six (29%) had progressive disease. No partial or complete responses were noted. Seven patients had a decrease in CA-125; four had a20% drop. RGD-specific PCR showed the presence of study vector in ascites of 16 patients. Seven revealed an increase in virus after day 3, suggesting replication of Ad5-Δ24-RGD. Minimal wild-type virus generation was detected. Viral shedding studies showed insignificant shedding in the serum, saliva, and urine. Anti-adenoviral neutralizing antibody effects were prevalent.This study, the first to evaluate an infectivity-enhanced CRAd in human cancer, shows the feasibility, safety, potential antitumor response, and biological activity of this approach in ovarian cancer. Further evaluation of infectivity enhanced virotherapy approaches for malignant gynecologic diseases is warranted.

Published
2010

213. Laser Microdissection

Author

Frost, Andra R., primary, Eltoum, Isam‐Eldin, additional, Siegal, Gene P., additional, Emmert‐Buck, Michael R., additional, and Tangrea, Michael A., additional

Published
2015
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215. Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage

Author

Sas, Kelli M., primary, Yin, Hong, additional, Fitzgibbon, Wayne R., additional, Baicu, Catalin F., additional, Zile, Michael R., additional, Steele, Stacy L., additional, Amria, May, additional, Saigusa, Takamitsu, additional, Funk, Jason, additional, Bunni, Marlene A., additional, Siegal, Gene P., additional, Siroky, Brian J., additional, Bissler, John J., additional, and Bell, P. Darwin, additional

Published
2015
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216. Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS

Author

Watson, Jennifer A., primary, Bhattacharyya, Bula J., additional, Vaden, Jada H., additional, Wilson, Julie A., additional, Icyuz, Mert, additional, Howard, Alan D., additional, Phillips, Edward, additional, DeSilva, Tara M., additional, Siegal, Gene P., additional, Bean, Andrew J., additional, King, Gwendalyn D., additional, Phillips, Scott E., additional, Miller, Richard J., additional, and Wilson, Scott M., additional

Published
2015
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218. Targeting the effector domain of the myristoylated alanine rich C-kinase substrate enhances lung cancer radiation sensitivity

Author

ROHRBACH, TIMOTHY D., primary, JARBOE, JOHN S., additional, ANDERSON, JOSHUA C., additional, TRUMMELL, HOA Q., additional, HICKS, PATRICIA H., additional, WEAVER, ALICE N., additional, YANG, EDDY S., additional, OSTER, ROBERT A., additional, DESHANE, JESSY S., additional, STEELE, CHAD, additional, SIEGAL, GENE P., additional, BONNER, JAMES A., additional, and WILLEY, CHRISTOPHER D., additional

Published
2014
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220. Alterations in human breast cancer adhesion-motility in response to changes in cell surface glycoproteins displaying alpha-L-fucose moieties

Author

Yuan, Kun, Kucik, Dennis, Singh, Raj K., Listinsky, Catherine M., Listinsky, Jay J., and Siegal, Gene P.

Subjects
alpha-L-Fucosidase, Endothelial Cells, Oligosaccharides, Breast Neoplasms, Intercellular Adhesion Molecule-1, Article, P-Selectin, Cell Movement, Cell Line, Tumor, Cell Adhesion, Humans, Female, E-Selectin, Sialyl Lewis X Antigen, Fucose, Glycoproteins
Abstract

Glycosylation of proteins plays multiple roles in cell-cell and cell-matrix interactions. Fucose is a monosaccharide associated with glycosylation events and is known to be over-expressed in many malignant tumors. By using alpha-L-fucosidase (alpha-L-fase), a glycosidase that specifically removes alpha-L-fucose (alpha-L-f), we have examined the potential effects of defucosylation on tumor functions, focusing on tumor progression in the context of the interaction of tumor cells with the extracellular microenvironment. In this submission, we report that alpha-L-fase treatment decreases, in static assays, tumor cell adhesion to a wide variety of ECM components including fibronectin, laminin, collagen I, hyaluronic acid and the complex human biomatrix, HuBiogel(R). By immunofluorescence, co-localization of beta1 integrin and alpha-L-f was found to decrease accordingly. Sialyl Lewis X, an alpha-L-f-containing tetrasaccharide, which modulates the rolling of leukocytes and tumor cells on endothelium, was found to be diminished on human breast cancer cells after alpha-L-fase treatment. Using a dynamic flow chamber system, we were able to determine that defucosylation impaired the rolling of mammary cancer cells on human umbilical vein endothelial cells while significantly increasing their flow speed. Further, the rolling capability of these defucosylated tumor cells was also impaired on purified E and P-selectin matrices. Based on these data, we hypothesize that decreased fucosylation impairs the interaction between tumor cells and their external milieu, which in turn, affects key cell functions modulating tumor progression. Building on our previous studies which demonstrated alpha-L-fase decreased tumor cell invasion while significantly reducing MMP-9 activity, when added to the fact that decreased adhesion on HUVEC occurs in the presence of alpha-L-fase also leads us to propose that defucosylation may modulate metastasis, and thus provides a promising additional glycobiotic target for novel therapies.

Published
2008

223. Prognostic Value of E-Cadherin and b-Catenin in Triple-Negative Breast Cancer.

Author

Tiansheng Shen, Kui Zhang, Siegal, Gene P., and Shi Wei

Subjects
CADHERINS, CATENINS, TRIPLE-negative breast cancer
Abstract

Objectives: To analyze the expression of E-cadherin and β-catenin in triple-negative breast cancer (TNBC) to assess their prognostic significance. Methods: The expression of E-cadherin and β-catenin was examined semiquantitatively and correlated with other pathologic factors and survival outcomes. Results: Of 72 consecutive TNBCs, 56% showed reduced membranous expression of E-cadherin or β-catenin, with a strong correlation to each other. Of the clinicopathologic factors analyzed, tumor size and nodal status were significantly associated with overall survival and disease-specific survival, while the latter remained an independent factor by multivariate analysis. Reduced E-cadherin and β-catenin were both significantly associated with a poor overall survival and disease-specific survival by univariate and multivariate analyses. Conclusions: E-cadherin and β-catenin expression provides discriminative prognostic power independent of conventional pathologic factors, thus further reinforcing the important role of cell adhesion molecules in the process of tumor metastasis, especially in TNBC. [ABSTRACT FROM AUTHOR]

Published
2016
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227. Virotherapy

Author

Zhu, Zeng B., primary, Smith, Bruce F., additional, Siegal, Gene P., additional, and Curiel, David T., additional

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231. Therapeutic Targeting of Src Kinase in Myofibroblast Differentiation and Pulmonary Fibrosis

Author

Hu, Meng, primary, Che, Pulin, additional, Han, Xiaosi, additional, Cai, Guo-Qiang, additional, Liu, Gang, additional, Antony, Veena, additional, Luckhardt, Tracy, additional, Siegal, Gene P., additional, Zhou, Yong, additional, Liu, Rui-ming, additional, Desai, Leena P., additional, O’Reilly, Philip J., additional, Thannickal, Victor J., additional, and Ding, Qiang, additional

Published
2014
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237. Enhancement of Antitumor Immunity in Lung Cancer by Targeting Myeloid-Derived Suppressor Cell Pathways

Author

Sawant, Anandi, primary, Schafer, Cara C., additional, Jin, Tong Huan, additional, Zmijewski, Jaroslaw, additional, Tse, Hubert M., additional, Roth, Justin, additional, Sun, Zhihuan, additional, Siegal, Gene P., additional, Thannickal, Victor J., additional, Grant, Stefan C., additional, Ponnazhagan, Selvarangan, additional, and Deshane, Jessy S., additional

Published
2013
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238. Apoptosis and Tumorigenesis in Human Cholangiocarcinoma Cells : Involvement of Fas/APO-1 (CD95) and Calmodulin

Author

Pan, George, Vickers, Selwyn M., Pickens, Allan, Phillips, John O., Ying, Weizhong, Thompson, John A., Siegal, Gene P., and McDonald, Jay M.

Subjects
Transplantation, Heterologous, Estrogen Antagonists, Mice, Nude, Apoptosis, Trifluoperazine, Cholangiocarcinoma, Mice, Tamoxifen, Bile Ducts, Intrahepatic, Bile Duct Neoplasms, Calmodulin, Tumor Cells, Cultured, Animals, Humans, Female, fas Receptor, hormones, hormone substitutes, and hormone antagonists, Neoplasm Transplantation, Regular Articles
Abstract

We have previously demonstrated that tamoxifen inhibits the growth of human cholangiocarcinoma cells in culture and inhibits tumor growth when cells are injected into nude mice. However, the mechanism of action of tamoxifen remains unknown. Here we demonstrate that tamoxifen and trifluoperazine, both potent calmodulin antagonists, induce apoptosis in vitro, probably acting via the Fas system, in human cholangiocarcinoma cells. Human cholangiocarcinoma cell lines heterogeneously express Fas antigen on their surface. Fas-negative and Fas-positive surface-expressing cells were isolated, cloned, and cultured. Fas antibody, tamoxifen, and trifluoperazine induced dose-dependent apoptosis only in Fas-positive cells; Fas-negative cells were unaffected. Furthermore, apoptosis induced by tamoxifen in Fas-positive cells was blocked by an inhibitory Fas antibody. Tamoxifen was not acting through an anti-estrogenic mechanism, because neither Fas-negative nor Fas-positive cells expressed estrogen receptors and the pure anti-estrogen compound, ICI 182780, did not induce apoptosis in either cell line. Fas-negative cells, but not Fas-positive cells, were able to produce tumors when subcutaneously injected into nude mice. These findings suggest Fas may be a candidate oncogene involved in the pathogenesis of cholangiocarcinoma. Furthermore, the similarity between the pro-apoptotic effects of tamoxifen and trifluoperazine support an underlying molecular mechanism for Fas-mediated apoptosis that involves calmodulin.

Published
1999

241. A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer

Author

Kim, Kenneth H., primary, Dmitriev, Igor P., additional, Saddekni, Souheil, additional, Kashentseva, Elena A., additional, Harris, Raymond D., additional, Aurigemma, Rosemarie, additional, Bae, Sejong, additional, Singh, Karan P., additional, Siegal, Gene P., additional, Curiel, David T., additional, and Alvarez, Ronald D., additional

Published
2013
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242. Erratum to “Elevated levels of NO are localized to distal airways in asthma”

Author

Anderson, John T., primary, Zeng, Meiqin, additional, Li, Qian, additional, Stapley, Ryan, additional, Ray Moore II, Doyle, additional, Chenna, Balachandra, additional, Fineberg, Naomi, additional, Zmijewski, Jaroslaw, additional, Eltoum, Isam-Eldin, additional, Siegal, Gene P., additional, Gaggar, Amit, additional, Barnes, Stephen, additional, Velu, Sadanandan E., additional, Thannickal, Victor J., additional, Abraham, Edward, additional, Patel, Rakesh P., additional, Lancaster, Jack R., additional, Chaplin, David D., additional, Dransfield, Mark T., additional, and Deshane, Jessy S., additional

Published
2013
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