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656 results on '"Goodfellow, Paul J."'

111. Ribosomal DNA methylation in patients with endometrial carcinoma

Author

Powell, Matthew A., Mutch, David G., Rader, Janet S., Herzog, Thomas J., Huang, Tim Hui-Ming, and Goodfellow, Paul J.

Subjects
Cancer -- Genetic aspects, Endometrial cancer -- Genetic aspects, Cancer patients -- Health aspects, DNA -- Genetic aspects, Ribosomes -- Genetic aspects, Methylation -- Genetic aspects, Genetic markers -- Physiological aspects, Health
Published
2002

115. Functional characterization of recurrent FOXA2 mutations seen in endometrial cancers

Author

Neff, Robert, Rush, Craig M., Smith, Blair, Backes, Floor J., Cohn, David E., and Goodfellow, Paul J.

Subjects
Transcription, Genetic, respiratory system, Cadherins, Article, Cell Line, Endometrial Neoplasms, DNA-Binding Proteins, Protein Transport, HEK293 Cells, Cell Line, Tumor, embryonic structures, Mutation, Hepatocyte Nuclear Factor 3-beta, Humans, Female, reproductive and urinary physiology
Abstract

FOXA2, a member of the forkhead family of DNA-binding proteins, is frequently mutated in uterine cancers. Most of the mutations observed in uterine cancers are frameshifts and stops. FOXA2 is considered to be a driver gene in uterine cancers, functioning as a haploinsufficient tumor suppressor. The functional consequences of FOXA2 mutations, however, have not yet been determined. We evaluated the effects that frameshift mutations as well as a recurrent missense mutation have on FOXA2 transcriptional activity. Recurrent N-terminal frameshifts resulted in truncated proteins that failed to translocate to the nucleus and have no transcriptional activity using an E-cadherin/luciferase reporter assay. Protein abundance was reduced for the recurrent p.S169W mutation, as was transcriptional activity. A C-terminal frameshift mutation had increased FOXA2 levels evidenced by both Western blot and immunofluorescence. Given that FOXA2 is a recognized activator of E-cadherin (CDH1) expression and E-cadherin’s potential role in epithelial-to-mesenchymal transition in a wide range of cancer types, we tested the hypothesis that FOXA2 mutations in primary uterine cancer specimens would be associated with reduced CDH1 transcript levels. qRT-PCR revealed significantly lower levels of CDH1 expression in primary tumors with FOXA2 mutations. Our findings in vitro and in vivo suggest that reduced transcriptional activity associated with FOXA2 mutations in uterine cancers is likely to contribute to pro-tumorigenic changes in gene expression.

Published
2018

116. Evaluating the efficacy of enzalutamide and the development of resistance in a preclinical mouse model of type-I endometrial carcinoma

Author

Koivisto, Christopher S., primary, Parrish, Melodie, additional, Bonala, Santosh B., additional, Ngoi, Soo, additional, Torres, Adrian, additional, Gallagher, James, additional, Sanchez-Hodge, Rebekah, additional, Zeinner, Victor, additional, Nahhas, Georges J., additional, Liu, Bei, additional, Cohn, David E., additional, Backes, Floor J., additional, Goodfellow, Paul J., additional, Chamberlin, Helen M., additional, and Leone, Gustavo, additional

Published
2019
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117. Dicer1 Phosphomimetic Promotes Tumor Progression and Dissemination

Author

Aryal, Neeraj K., primary, Pant, Vinod, additional, Wasylishen, Amanda R., additional, Rimel, Bobbie J., additional, Baseler, Laura, additional, El-Naggar, Adel K., additional, Mutch, David G., additional, Goodfellow, Paul J., additional, Arur, Swathi, additional, and Lozano, Guillermina, additional

Published
2019
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119. Familial Melanoma and Pancreatic Cancer

Author

Ciotti, Paola, Strigini, Paolo, Bianchi-Scarra, Giovanna, Wright, Fred A., Thomas, Ronald G., Bergman, Wilma, Gruis, Nelleke, Goldstein, Alisa M., Tucker, Margaret A., Whelan, Alison J., Bartsch, Detlef, and Goodfellow, Paul J.

Published
1996
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122. RET gene and its implications for cancer

Author

Goodfellow, Paul J. and Wells, Samuel A., Jr.

Subjects
Proto-oncogenes -- Health aspects, Cancer -- Development and progression, Tumors -- Development and progression, Health
Published
1995

128. Adipokines Deregulate Cellular Communication via Epigenetic Repression of Gap Junction Loci in Obese Endometrial Cancer

Author

Polusani, Srikanth R., primary, Huang, Yi-Wen, additional, Huang, Guangcun, additional, Chen, Chun-Wei, additional, Wang, Chiou-Miin, additional, Lin, Li-Ling, additional, Osmulski, Pawel, additional, Lucio, Nicholas D., additional, Liu, Lu, additional, Hsu, Ya-Ting, additional, Zhou, Yufan, additional, Lin, Chun-Lin, additional, Aguilera-Barrantes, Irene, additional, Valente, Philip T., additional, Kost, Edward R., additional, Chen, Chun-Liang, additional, Shim, Eun Yong, additional, Lee, Sang Eun, additional, Ruan, Jianhua, additional, Gaczynska, Maria E., additional, Yan, Pearlly, additional, Goodfellow, Paul J., additional, Mutch, David G., additional, Jin, Victor X., additional, Nicholson, Bruce J., additional, Huang, Tim H.-M., additional, and Kirma, Nameer B., additional

Published
2019
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134. Frequent PIK3CA Mutations in Colorectal and Endometrial Cancer with Double Somatic Mismatch Repair Mutations

Author

Cohen, Stacey A., Turner, Emily H., Beightol, Mallory B., Jacobson, Angela, Gooley, Ted A., Salipante, Stephen J., Haraldsdottir, Sigurdis, Smith, Christina, Scroggins, Sheena, Tait, Jonathan F., Grady, William M., Lin, Edward H., Cohn, David E., Goodfellow, Paul J., Arnold, Mark W., de la Chapelle, Albert, Pearlman, Rachel, Hampel, Heather, and Pritchard, Colin C.

Subjects
Male, Proto-Oncogene Proteins B-raf, Class I Phosphatidylinositol 3-Kinases, DNA Mutational Analysis, PTEN Phosphohydrolase, Membrane Proteins, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Mismatch Repair, Article, Endometrial Neoplasms, GTP Phosphohydrolases, Proto-Oncogene Proteins p21(ras), Phosphatidylinositol 3-Kinases, Phenotype, Mutation, Humans, Female, Microsatellite Instability, Prospective Studies, Colorectal Neoplasms
Abstract

Some colorectal and endometrial tumors with microsatellite instability not attributable to MLH1 hypermethylation or germline mutations contain 2 or more somatic mutations in genes encoding mismatch repair (MMR) proteins. We sought to define the molecular phenotype of this newly recognized tumor subtype.From 2 prospective studies of the efficacy of screening for Lynch syndrome, we identified patients with colorectal and endometrial tumors who had 2 or more somatic (but not germline) mutations in genes encoding MMR proteins (double somatic). We determined the frequencies of tumor mutations in PIK3CA, BRAF, KRAS, NRAS, and PTEN by targeted next-generation sequencing and used logistic-regression models to compare them with those from patients with Lynch syndrome, MLH1-hypermethylated, or microsatellite-stable tumors. We validated our findings using independent data sets from The Cancer Genome Atlas.Among colorectal cancer cases, we found that 14 of 21 (67%) patients with double somatic tumors also had PIK3CA mutations, compared with 4 of 18 (22%) tumors from patients with Lynch syndrome, 2 of 10 (20%) tumors with MLH1 hypermethylation, and 12 of 78 (15%) tumors with microsatellite stability (P.0001 for patients with double somatic tumors vs other subgroups). Mutations in PIK3CA were detected in all 13 patients with double somatic endometrial cancers (P = .04 compared with other subgroups). We did not detect BRAF mutations in patients with double somatic colorectal tumors or Lynch syndrome. We found highly similar results in a validation cohort from The Cancer Genome Atlas (113 patients with colorectal tumors, 178 endometrial tumors); 100% of double somatic cases had a somatic mutation in PIK3CA (P.0001 compared with other subgroups).Most patients with colorectal or endometrial tumors with 2 or more somatic (but not germline) mutations in MMR proteins also have mutations in PIK3CA; mutations in PIK3CA are detected at substantially higher frequencies in these double somatic tumors than in other microsatellite-instability subgroups. PIK3CA mutation status might be used to identify a specific group of colorectal tumors, and to select treatment or determine prognosis.

Published
2016

135. MAX Mutations in Endometrial Cancer: Clinicopathologic Associations and Recurrent MAX p.His28Arg Functional Characterization

Author

Walker, Christopher J, primary, Rush, Craig M, additional, Dama, Paola, additional, O’Hern, Matthew J, additional, Cosgrove, Casey M, additional, Gillespie, Jessica L, additional, Zingarelli, Roman A, additional, Smith, Blair, additional, Stein, Maggie E, additional, Mutch, David G, additional, Shakya, Reena, additional, Chang, Chia-Wen, additional, Selvendiran, Karuppaiyah, additional, Song, Jonathan W, additional, Cohn, David E, additional, and Goodfellow, Paul J, additional

Published
2017
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138. Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials

Author

MacKay, Helen J., primary, Levine, Douglas A., additional, Bae-Jump, Victoria L., additional, Bell, Daphne W., additional, McAlpine, Jessica N., additional, Santin, Alessandro, additional, Fleming, Gini F., additional, Mutch, David G., additional, Nephew, Kenneth P., additional, Wentzensen, Nicolas, additional, Goodfellow, Paul J., additional, Dorigo, Oliver, additional, Nijman, Hans W., additional, Broaddus, Russell, additional, and Kohn, Elise C., additional

Published
2017
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139. Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence

Author

Sunkel, Benjamin, primary, Wu, Dayong, additional, Chen, Zhong, additional, Wang, Chiou-Miin, additional, Liu, Xiangtao, additional, Ye, Zhenqing, additional, Horning, Aaron M., additional, Liu, Joseph, additional, Mahalingam, Devalingam, additional, Lopez-Nicora, Horacio, additional, Lin, Chun-Lin, additional, Goodfellow, Paul J., additional, Clinton, Steven K., additional, Jin, Victor X., additional, Chen, Chun-Liang, additional, Huang, Tim H.-M., additional, and Wang, Qianben, additional

Published
2017
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142. Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study

Author

McMeekin, D. Scott, primary, Tritchler, David L., additional, Cohn, David E., additional, Mutch, David G., additional, Lankes, Heather A., additional, Geller, Melissa A., additional, Powell, Matthew A., additional, Backes, Floor J., additional, Landrum, Lisa M., additional, Zaino, Richard, additional, Broaddus, Russell D., additional, Ramirez, Nilsa, additional, Gao, Feng, additional, Ali, Shamshad, additional, Darcy, Kathleen M., additional, Pearl, Michael L., additional, DiSilvestro, Paul A., additional, Lele, Shashikant B., additional, and Goodfellow, Paul J., additional

Published
2016
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143. MonoSeq Variant Caller Reveals Novel Mononucleotide Run Indel Mutations in Tumors with Defective DNA Mismatch Repair

Author

Walker, Christopher J., primary, Miranda, Mario A., additional, O'Hern, Matthew J., additional, Blachly, James S., additional, Moyer, Cassandra L., additional, Ivanovich, Jennifer, additional, Kroll, Karl W., additional, Eisfeld, Ann-Kathrin, additional, Sapp, Caroline E., additional, Mutch, David G., additional, Cohn, David E., additional, Bundschuh, Ralf, additional, and Goodfellow, Paul J, additional

Published
2016
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148. Lithium and inhibition of GSK3β as a potential therapy for serous ovarian cancer

Author

Novetsky, Akiva P., Thompson, Dominic M., Zighelboim, Israel, Thaker, Premal H., Powell, Matthew A., Mutch, David G., and Goodfellow, Paul J.

Subjects
Ovarian Neoplasms, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Cell Cycle, Primary Cell Culture, Tumor Cells, Cultured, Humans, Female, Lithium Chloride, Protein Kinase Inhibitors, Article, Cell Proliferation, Cystadenocarcinoma, Serous
Abstract

Lithium chloride (LiCl) has been shown to demonstrate anticancer properties at supratherapeutic doses. This study was designed to determine whether LiCl, as a single agent or in combination with cytotoxic agents, reduces ovarian cancer cell growth and metabolic activity at clinically achievable levels.We studied the effects of LiCl on 2 high-grade serous ovarian cancer cell lines, SKOV3 and OVCA 433, and primary cultures developed from ascitic fluid collected from patients with metastatic high-grade serous ovarian cancer. We assessed proliferation and metabolism using cell cycle analysis, MTT assays, and cellular proliferation and clonogenic potential assays.Treatment with 1 mM LiCl had no effect on the cell cycle distribution or metabolic activity of the SKOV3 and OVCA 433 cell lines. Combination treatment with cisplatin or paclitaxel led to statistically significant decreases in metabolic activity in the OVCA 433 cell line and 50% of cultures investigated. The decreased metabolic activity was not, however, associated with decreased cell growth or clonogenic potential.Combination treatment with LiCl and cytotoxic agents at physiologically achievable drug concentrations reduces ovarian cancer cell metabolism but does not appear to affect cellular proliferation. The potential for combined lithium/cytoxic therapies appears to be limited based on our analysis of both established cell lines and short-term ovarian cancer cultures.

Published
2013

149. Assessment of Tumor Sequencing as a Replacement for Lynch Syndrome Screening and Current Molecular Tests for Patients With Colorectal Cancer.

Author

Hampel, Heather, Pearlman, Rachel, Beightol, Mallory, Zhao, Weiqiang, Jones, Daniel, Frankel, Wendy L., Goodfellow, Paul J., Yilmaz, Ahmet, Miller, Kristin, Bacher, Jason, Jacobson, Angela, Paskett, Electra, Shields, Peter G., Goldberg, Richard M., de la Chapelle, Albert, Shirts, Brian H., and Pritchard, Colin C.

Published
2018
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150. MAX Mutations in Endometrial Cancer: Clinicopathologic Associations and Recurrent MAX p.His28Arg Functional Characterization.

Author

Walker, Christopher J., Rush, Craig M., Dama, Paola, O'Hern, Matthew J., Cosgrove, Casey M., Gillespie, Jessica L., Zingarelli, Roman A., Smith, Blair, Stein, Maggie E., Mutch, David G., Shakya, Reena, Chia-Wen Chang, Selvendiran, Karuppaiyah, Song, Jonathan W., Cohn, David E., Goodfellow, Paul J., and Chang, Chia-Wen

Subjects
ENDOMETRIAL cancer, CANCER genetics, GENETIC mutation, TRANSCRIPTION factors, IMMUNOPRECIPITATION, GENETICS, AMINO acids, ANIMAL populations, ANIMALS, ARGININE, CANCER invasiveness, CELL culture, DISEASE susceptibility, EPITHELIAL cells, GENETIC techniques, MICE, PROTEINS, RESEARCH funding, ENDOMETRIAL tumors, HISTIDINE, PATHOLOGIC neovascularization
Abstract

Background: Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes.Methods: MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed. EC cell lines stably expressing MAXH28R were established and used for functional experiments. DNA binding was examined using electrophoretic mobility shift assays and chromatin immunoprecipitation. Transcriptional profiling was performed with microarrays. Murine flank (six to 11 mice per group) and intraperitoneal tumor models were used for in vivo studies. Vascularity of xenografts was assessed by MECA-32 immunohistochemistry. The paracrine pro-angiogenic nature of MAXH28R-expressing EC cells was tested using microfluidic HUVEC sprouting assays and VEGFA enzyme-linked immunosorbent assays. All statistical tests were two-sided.Results: Twenty-two of 509 tumors harbored mutations in MAX, including 12 tumors with the p.His28Arg mutation. Patients with a MAX mutation had statistically significantly reduced recurrence-free survival (hazard ratio = 4.00, 95% confidence interval = 1.15 to 13.91, P = .03). MAXH28R increased affinity for canonical E-box sequences, and MAXH28R-expressing EC cells dramatically altered transcriptional profiles. MAXH28R-derived xenografts statistically significantly increased vascular area compared with MAXWT and empty vector tumors (P = .003 and P = .008, respectively). MAXH28R-expressing EC cells secreted nearly double the levels of VEGFA compared with MAXWT cells (P = .03, .005, and .005 at 24, 48, and 72 hours, respectively), and conditioned media from MAXH28R cells increased sprouting when applied to HUVECs.Conclusion: These data highlight the importance of MAX mutations in EC and point to increased vascularity as one mechanism contributing to clinical aggressiveness of EC. [ABSTRACT FROM AUTHOR]

Published
2018
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