Read by QxMD icon Read


Shuhei Enjoji, Ryotaro Yabe, Shunya Tsuji, Kazuhiro Yoshimura, Hideyoshi Kawasaki, Masashi Sakurai, Yusuke Sakai, Hiroko Takenouchi, Shigefumi Yoshino, Shoichi Hazama, Hiroaki Nagano, Hiroko Oshima, Masanobu Oshima, Michael P Vitek, Tetsuya Matsuura, Yoshitaka Hippo, Tatsuya Usui, Takashi Ohama, Koichi Sato
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possesses the ability to self-renew and dedifferentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown...
March 2018: Molecular Cancer Research: MCR
Gadi Shlomai, Zara Zelenko, Irini Markella Antoniou, Marilyn Stasinopoulos, Aviva Tobin-Hess, Michael P Vitek, Derek LeRoith, Emily Jane Gallagher
Hyperinsulinemia is associated with a decrease in breast cancer recurrence-free survival and overall survival. Inhibition of insulin receptor signaling is associated with glycemic dysregulation. SET is a direct modulator of PP2A, which negatively regulates the PI3K/AKT/mTOR pathway. OP449, a SET inhibitor, decreases AKT/mTOR activation. The effects of OP449 treatment on breast cancer growth in the setting of pre-diabetes, and its metabolic implications are currently unknown. We found that the volumes and weights of human MDA-MB-231 breast cancer xenografts were greater in hyperinsulinemic mice compared with controls ( P  < 0...
October 2017: Endocrine-related Cancer
Nameeta P Richard, Raffaella Pippa, Megan M Cleary, Alka Puri, Deanne Tibbitts, Shawn Mahmood, Dale J Christensen, Sophia Jeng, Shannon McWeeney, A Thomas Look, Bill H Chang, Jeffrey W Tyner, Michael P Vitek, María D Odero, Rosalie Sears, Anupriya Agarwal
Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated in T-ALL cell lines and primary samples compared to healthy T cells. Treatment of T-ALL cells with the SET antagonist OP449 restored the activity of PP2A and reduced SET interaction with the PP2A catalytic subunit, resulting in a decrease in cell viability and c-MYC expression in a dose-dependent manner...
December 20, 2016: Oncotarget
Xiaoyong Hu, Consuelo Garcia, Ladan Fazli, Martin Gleave, Michael P Vitek, Marilyn Jansen, Dale Christensen, David J Mulholland
The PP2A signaling axis regulates multiple oncogenic drivers of castration resistant prostate cancer (CRPC). We show that targeting the endogenous PP2A regulator, SET (I2PP2A), is a viable strategy to inhibit prostate cancers that are resistant to androgen deprivation therapy. Our data is corroborated by analysis of prostate cancer patient cohorts showing significant elevation of SET transcripts. Tissue microarray analysis reveals that elevated SET expression correlates with clinical cancer grading, duration of neoadjuvant hormone therapy (NHT) and time to biochemical recurrence...
November 13, 2015: Scientific Reports
Shuhei Enjoji, Ryotaro Yabe, Nobuyuki Fujiwara, Shunya Tsuji, Michael P Vitek, Takuya Mizuno, Takayuki Nakagawa, Tatsuya Usui, Takashi Ohama, Koichi Sato
Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein levels have been reported to exacerbate human tumor progression. The role of SET in canine melanoma, however, has not been understood. Here, we investigated the potential therapeutic role for SET inhibitors in canine melanoma...
November 2015: Journal of Veterinary Medical Science
Kavitha Ramaswamy, Barbara Spitzer, Alex Kentsis
Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that is required for normal cell growth and development. PP2A is a potent tumor suppressor, which is inactivated in cancer cells as a result of genetic deletions and mutations. In myeloid leukemias, genes encoding PP2A subunits are generally intact. Instead, PP2A is functionally inhibited by post-translational modifications of its catalytic C subunit, and interactions with negative regulators by its regulatory B and scaffold A subunits. Here, we review the molecular mechanisms of genetic and functional inactivation of PP2A in human cancers, with a particular focus on human acute myeloid leukemias (AML)...
2015: Frontiers in Oncology
Mahnaz Janghorban, Amy S Farrell, Brittany L Allen-Petersen, Carl Pelz, Colin J Daniel, Jessica Oddo, Ellen M Langer, Dale J Christensen, Rosalie C Sears
The transcription factor c-MYC is stabilized and activated by phosphorylation at serine 62 (S62) in breast cancer. Protein phosphatase 2A (PP2A) is a critical negative regulator of c-MYC through its ability to dephosphorylate S62. By inactivating c-MYC and other key signaling pathways, PP2A plays an important tumor suppressor function. Two endogenous inhibitors of PP2A, I2PP2A, Inhibitor-2 of PP2A (SET oncoprotein) and cancerous inhibitor of PP2A (CIP2A), inactivate PP2A and are overexpressed in several tumor types...
June 24, 2014: Proceedings of the National Academy of Sciences of the United States of America
Amy S Farrell, Brittany Allen-Petersen, Colin J Daniel, Xiaoyan Wang, Zhiping Wang, Sarah Rodriguez, Soren Impey, Jessica Oddo, Michael P Vitek, Charles Lopez, Dale J Christensen, Brett Sheppard, Rosalie C Sears
UNLABELLED: Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Several pathways that have shown to contribute to pancreatic cancer progression are negatively regulated by the tumor suppressor protein phosphatase 2A (PP2A)...
June 2014: Molecular Cancer Research: MCR
Paolo Neviani, Danilo Perrotti
The protein phosphatase 2A (PP2A) tumor suppressor is inactivated in different leukemias through the activity of its endogenous inhibitors (e.g., SET), which are aberrantly regulated by oncogenic tyrosine kinases. Like other effective and nontoxic PP2A-activating drugs (PAD), OP449 inhibits SET and impairs leukemogenesis. This further supports the immediate use of PADs in patients with leukemia.
April 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Anupriya Agarwal, Ryan J MacKenzie, Raffaella Pippa, Christopher A Eide, Jessica Oddo, Jeffrey W Tyner, Rosalie Sears, Michael P Vitek, María D Odero, Dale J Christensen, Brian J Druker
PURPOSE: The SET oncoprotein, a potent inhibitor of the protein phosphatase 2A (PP2A), is overexpressed in leukemia. We evaluated the efficacy of SET antagonism in chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) cell lines, a murine leukemia model, and primary patient samples using OP449, a specific, cell-penetrating peptide that antagonizes SET's inhibition of PP2A. EXPERIMENTAL DESIGN: In vitro cytotoxicity and specificity of OP449 in CML and AML cell lines and primary samples were measured using proliferation, apoptosis, and clonogenic assays...
April 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nobuyuki Fujiwara, Hideyoshi Kawasaki, Ryotaro Yabe, Dale J Christensen, Michael P Vitek, Takuya Mizuno, Koichi Sato, Takashi Ohama
Lymphoma is one of the most common malignant tumors in canine. Chemotherapy results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within a year. Protein phosphatase 2A (PP2A) acts as a tumor suppressor and plays a critical role in mammalian cell transformation. Increased protein levels of SET, endogenous PP2A inhibitor, have been reported to correlate with poor prognosis in human leukemia. Here, we test the potential therapeutic role for a SET antagonist in canine lymphoma...
2013: Journal of Veterinary Medical Science
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"