Search

Your search keyword '"Yang, Sherry X."' showing total 32 results
Start Over Author "Yang, Sherry X." Search Limiters Available in Library Collection
32 results on '"Yang, Sherry X."'

3. Upregulation of TET2 and Resistance to DNA Methyltransferase (DNMT) Inhibitors in DNMT1 -Deleted Cancer Cells.

Author

Laranjeira, Angelo B. A., Nguyen, Dat, Pelosof, Lorraine C., Doroshow, James H., and Yang, Sherry X.

Subjects
TUMOR suppressor proteins, GENE expression, SUPPRESSOR cells, GENETIC regulation, RENAL cancer, P16 gene
Abstract

Simple Summary: Ten-eleven-translocation (TET) 2 is implicated in human cancers such as lung, breast, skin, and kidney cancers, T-cell lymphomas, and leukemia. It is unclear whether TET2 is involved in the re-expression of the p16 tumor suppressor, which was partially silenced by CDKN2A gene methylation. The effect of DNA methyltransferase (DNMT) 1 gene status on TET2 expression following DNMT inhibitor treatment remains unknown in cancer. We found that deleting the DNMT1 gene made cancer cells prone to increased TET2 expression and re-expression of p16 after drug treatment. TET2 is involved in the demethylation of the CDKN2A gene and activation of p16 expression, and concomitant resistance to DNMT inhibitors when DNMT1 is obliterated. The long-sought data for the first time revealed a link between TET2 expression and the activation of p16 expression. The findings should have an impact on reactivating tumor suppressors and cancer treatment. Background: Ten-eleven-translocation (TET) 2 is a member of the TET family of proteins (TET1-3). DNMT1 gene deletion confers resistance to DNA methyltransferase (DNMT) inhibitors in colorectal, breast, and ovarian cancer cells. Currently, the effect of DNMT1 gene status on TET2 phenotype following DNMT inhibitor treatment is unclear in human malignancies. Methods: Human colorectal carcinoma HCT116 cells (DNMT+/+) and their isogenic DNMT1 knockout (DNMT1–/–) counterpart were treated with DNMT inhibitors. Expression of TET2 and tumor suppressor (p16ink4A and p15ink4B) proteins were examined by Western blot. Apoptosis and CDKN2A promoter demethylation following drug treatment were detected by Annexin-V apoptosis assay and methylation-specific PCR. Results: TET2 expression was robustly increased in DNMT1−/− cells by 0.5 µM and 5 µM decitabine and azacitidine treatment. Augmentation of TET2 expression was accompanied by re-expression of p16ink4A and p15ink4B proteins and CDKN2A promoter demethylation. TET2 upregulation and tumor suppressor re-expression were associated with resistance conferred by DNMT1 deletion. Treatment with 5-aza-4′-thio-2′-deoxycytidine at a low 0.5 µM dose only upregulated TET2 and reduced CDKN2A promoter methylation, and re-expression of p16ink4A in DNMT1−/− cells. DNMT inhibitors showed minimal effects on TET2 upregulation and re-expression of tumor suppressor proteins in cells with intact DNMT1. Conclusions: DNMT1 gene deletion made cancer cells prone to TET2 upregulation and activation of tumor suppressor expression upon DNMT inhibitor challenge. TET2 augmentation is concomitant with resistance to DNMT inhibitors in a DNMT1-deleted state. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

9. Additional file 1 of TET2 and DNMT3A mutations and exceptional response to 4′-thio-2′-deoxycytidine in human solid tumor models

Author

Yang, Sherry X., Hollingshead, Melinda, Rubinstein, Larry, Nguyen, Dat, Larenjeira, Angelo B. A., Kinders, Robert J., Difilippantonio, Michael, and Doroshow, James H.

Abstract

Additional file 1: Fig. S1. Inhibition of growth and TET2, and cell cycle arrest by T-dCyd in human solid tumor cell lines. Fig. S2. Effects of T-dCyd on DNMT3A/TET2-mutant NCI-H23 xenograft tumors in mice treated with 2 mg/kg T-dCyd by immunohistochemical and microscopic analyses (6 tumor samples per group). Fig. S3. Effects of T-dCyd on the induction of apoptosis in NCI-H23 cells. Fig. S4. Effects of T-dCyd on TET2 expression in DNMT3A/TET2-mutant NCI-H23 xenograft tumors.

Published
2021
Full Text
View/download PDF

19. Identification and Analysis of In Vivo VEGF Downstream Markers Link VEGF Pathway Activity with Efficacy of Anti-VEGF Therapies

Author

Brauer, Matthew J., primary, Zhuang, Guanglei, additional, Schmidt, Maike, additional, Yao, Jenny, additional, Wu, Xiumin, additional, Kaminker, Joshua S., additional, Jurinka, Stefanie S., additional, Kolumam, Ganesh, additional, Chung, Alicia S., additional, Jubb, Adrian, additional, Modrusan, Zora, additional, Ozawa, Tomoko, additional, James, C. David, additional, Phillips, Heidi, additional, Haley, Benjamin, additional, Tam, Rachel N.W., additional, Clermont, Anne C., additional, Cheng, Jason H., additional, Yang, Sherry X., additional, Swain, Sandra M., additional, Chen, Daniel, additional, Scherer, Stefan J., additional, Koeppen, Hartmut, additional, Yeh, Ru-Fang, additional, Yue, Peng, additional, Stephan, Jean-Philippe, additional, Hegde, Priti, additional, Ferrara, Napoleone, additional, Singh, Mallika, additional, and Bais, Carlos, additional

Published
2013
Full Text
View/download PDF

22. DNA Methyltransferase Inhibitor, Zebularine, Delays Tumor Growth and Induces Apoptosis in a Genetically Engineered Mouse Model of Breast Cancer

Author

Chen, Min, primary, Shabashvili, Daniel, additional, Nawab, Akbar, additional, Yang, Sherry X., additional, Dyer, Lisa M., additional, Brown, Kevin D., additional, Hollingshead, Melinda, additional, Hunter, Kent W., additional, Kaye, Frederic J., additional, Hochwald, Steven N., additional, Marquez, Victor E., additional, Steeg, Patricia, additional, and Zajac-Kaye, Maria, additional

Published
2012
Full Text
View/download PDF

27. Designing Phase 0 Cancer Clinical Trials

Author

Murgo, Anthony J., primary, Kummar, Shivaani, additional, Rubinstein, Larry, additional, Gutierrez, Martin, additional, Collins, Jerry, additional, Kinders, Robert, additional, Parchment, Ralph E., additional, Ji, Jiuping, additional, Steinberg, Seth M., additional, Yang, Sherry X., additional, Hollingshead, Melinda, additional, Chen, Alice, additional, Helman, Lee, additional, Wiltrout, Robert, additional, Tomaszewski, Joseph E., additional, and Doroshow, James H., additional

Published
2008
Full Text
View/download PDF

28. Cardiac Toxicity and Efficacy of Trastuzumab Combined with Pertuzumab in Patients with Trastuzumab-Insensitive Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

Author

Portera, Chia C., primary, Walshe, Janice M., additional, Rosing, Douglas R., additional, Denduluri, Neelima, additional, Berman, Arlene W., additional, Vatas, Ujala, additional, Velarde, Margarita, additional, Chow, Catherine K., additional, Steinberg, Seth M., additional, Nguyen, Diana, additional, Yang, Sherry X., additional, and Swain, Sandra M., additional

Published
2008
Full Text
View/download PDF

31. Immunohistochemical detection of poly(ADP-ribose) polymerase inhibition by ABT-888 in patients with refractory solid tumors and lymphomas

Author

Yang, Sherry X., Kummar, Shivaani, Steinberg, Seth M., Murgo, Anthony J., Gutierrez, Martin, Rubinstein, Larry, Nguyen, Dat, Kaur, Gurmeet, Chen, Alice P., Giranda, Vincent L, Tomaszewski, Joseph E., Doroshow, James H., and Phase 0 Working Group, The National Cancer Institute

Abstract

Purpose: Targeting the poly (ADP-ribose) polymerase (PARP) pathway for cancer treatment has been an active area of pre-clinical and clinical research.  We aimed to determine whether the PARP inhibitor ABT-888 hits its therapeutic target in tumors by immunohistochemistry during a Phase 0 trial conducted at the National Cancer Institute. Experimental design: The expression of poly (ADP-ribose) (PAR) and full size PARP-1 were quantitatively examined by immunohistochemistry in paraffin-embedded tumor biopsies at baseline and 3-24 h after a single oral dose (25 or 50 mg) of ABT-888. Results: Baseline PAR levels were moderate to high in three patients with non-Hodgkin lymphomas, and one each with small cell lung cancer, squamous cell carcinoma of the tongue, and melanoma; low in two patients with cutaneous T cell lymphoma and one with adenocarcinoma of external ear canal. A significant decrease in PAR (median decrease 30.2, range -13.1 to -69.8) was achieved after drug administration (n = 6 pairs; p = 0.03), whereas an increase in PARP-1 expression was observed in five of the six tumors.  This resulted in a decrease in the ratio of PAR to PARP-1 in tumor biopsies (median -6.76, range -0.41 to -22.59; p = 0.03). Conclusions: ABT-888 hits its therapeutic target by significantly reducing PAR levels and the ratio of PAR to PARP-1 in human tumor cells detected by immunohistochemistry. Baseline tumor PAR levels vary considerably among patients who entered this phase 0 study.  This underscores a need to investigate baseline PAR levels in association with response in future preclinical and clinical studies.

Published
2009
Full Text
View/download PDF

32. Cardiac toxicity and efficacy of trastuzumab combined with pertuzumab in patients with [corrected] human epidermal growth factor receptor 2-positive metastatic breast cancer.

Author

Portera CC, Walshe JM, Rosing DR, Denduluri N, Berman AW, Vatas U, Velarde M, Chow CK, Steinberg SM, Nguyen D, Yang SX, and Swain SM

Subjects
Adult, Aged, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms metabolism, Echocardiography, Female, Humans, Middle Aged, Receptor, ErbB-2 metabolism, Trastuzumab, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Heart drug effects, Ventricular Dysfunction, Left chemically induced
Abstract

Purpose: To evaluate safety and efficacy of trastuzumab with pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who had progressive disease on trastuzumab-based therapy., Experimental Design: Patients with measurable HER2(+) metastatic breast cancer, < or = 3 trastuzumab-based regimens, and left ventricular ejection fraction (LVEF) > or = 55% received 8 or 6 mg/kg trastuzumab and 840 mg pertuzumab i.v. followed by 6 mg/kg trastuzumab and 420 mg pertuzumab every 3 weeks. Cardiac evaluation and tumor response were assessed every 3 and 6 weeks, respectively., Results: Eleven patients received 64 cycles of trastuzumab plus pertuzumab. A total of 92 echocardiograms and 8 cardiac magnetic resonance imaging studies were done. With the lower limit of normal LVEF 55%, left ventricular systolic dysfunction was observed in six patients, three grade 1, two grade 2, and one grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The objective response rate was 18%. Two patients had partial responses, three had stable disease, and six had progressive disease. The median time to progression was 6 weeks. In baseline tumors from formalin-fixed paraffin-embedded primary and/or metastatic tumor biopsies, pHER2-Y1248 trended toward an increase in patients with partial response compared with those with stable disease/progressive disease (P = 0.095)., Conclusion: Trastuzumab plus pertuzumab may have clinical benefit in selected patients who have previously been treated with trastuzumab. Cardiac toxicity, although asymptomatic in most cases, was associated with this treatment. Further evaluation of efficacy of this combination is required to define the overall risks and benefits.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results