Neoplastic Stem Cells

Publication Title: 
Cancer Treatment and Research
Author(s): 
Cobleigh, M. A.
Publication Title: 
Epigenetics

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM).

Author(s): 
Pastori, Chiara
Daniel, Mark
Penas, Clara
Volmar, Claude-Henry
Johnstone, Andrea L.
Brothers, Shaun P.
Graham, Regina M.
Allen, Bryce
Sarkaria, Jann N.
Komotar, Ricardo J.
Wahlestedt, Claes
Ayad, Nagi G.
Publication Title: 
International Journal of Oncology

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. We described recently that tumor growth inhibiting cytostatic proline-rich polypeptide 1, (PRP-1) significantly upregulated tumor suppressor miRNAs, downregulated onco-miRNAs in human chondrosarcoma JJ012 cell line, compared to chondrocytes culture.

Author(s): 
Galoian, Karina
Qureshi, Amir
D'Ippolito, Gianluca
Schiller, Paul C.
Molinari, Marco
Johnstone, Andrea L.
Brothers, Shaun P.
Paz, Ana C.
Temple, H. T.
Publication Title: 
Neuro-Oncology

BACKGROUND: A proportion of glioblastoma stemlike cells (GSCs) expressing endothelial cell marker CDH5 (vascular-endothelial-cadherin or CD144) can transdifferentiate into endothelial cells and form blood vessels. However, the implications of CDH5 expression in gliomas and how it is regulated in GSCs remain to be clarified. METHODS: The mRNA and protein levels of CDH5 were detected in glioma samples and cultured cell lines, and the prognostic value of the CDH5 expression level for GBM patients was evaluated.

Author(s): 
Mao, Xing-Gang
Xue, Xiao-Yan
Wang, Liang
Zhang, Xiang
Yan, Ming
Tu, Yan-yang
Lin, Wei
Jiang, Xiao-Fan
Ren, Hong-Gang
Zhang, Wei
Song, Shao-Jun
Publication Title: 
Journal of Stem Cells

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc.

Author(s): 
Metri, Kashinath
Bhargav, Hemant
Chowdhury, Praerna
Koka, Prasad S.
Publication Title: 
Journal of Stem Cells

Cancer stem cells (CSCs) are stem-like tumor populations that are reported to contribute towards tumor growth, maintenance and recurrence after therapy. Hypoxia increases CSC fraction and promotes acquisition of a stem-cell-like state. Cancer stem cells are critically dependant on the hypoxia-inducible factor-1 (HIF-1) for survival, self-renewal, tumor growth and maintenance of their undifferentiated phenotype.

Author(s): 
Bhargav, Hemant
Metri, Kashinath
Raghuram, Nagarathna
Ramarao, Nagendra Hongasandra
Koka, Prasad S.
Publication Title: 
Hepatology (Baltimore, Md.)

Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the biosynthesis of S-adenosylmethionine. Hepatic MAT activity falls in chronic liver diseases, and mice lacking Mat1a are predisposed to liver injury and develop hepatocellular carcinoma (HCC) spontaneously by 18 months. The current work examined the hypothesis that liver cancer stem cells contribute to HCC in this model. Livers from 6- and 18-month-old Mat1a-knockout (KO) mice and their wild-type (WT) littermates were fractionated and isolated by flow cytometry.

Author(s): 
Rountree, C. Bart
Senadheera, Shantha
Mato, José M.
Crooks, Gay M.
Lu, Shelly C.
Publication Title: 
Hepatology (Baltimore, Md.)

Methionine adenosyltransferase (MAT) is an essential enzyme required for S-adenosylmethionine biosynthesis. Hepatic MAT activity falls during chronic liver injury, and mice lacking Mat1a develop spontaneous hepatocellular carcinoma by 18 months. We have previously demonstrated that CD133(+)CD45(-) oval cells isolated from 16-month-old Mat1a(-/-) mice represent a liver cancer stem cell population. The transforming growth factor beta (TGF-beta) pathway constitutes a central signaling network in proliferation, apoptosis, and tumorigenesis.

Author(s): 
Ding, Wei
Mouzaki, Marialena
You, Hanning
Laird, Joshua C.
Mato, Jose
Lu, Shelly C.
Rountree, C. Bart
Publication Title: 
Blood

Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ(12)-PGJ(3), a novel and naturally produced CyPG from the dietary fish-oil ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia.

Author(s): 
Hegde, Shailaja
Kaushal, Naveen
Ravindra, Kodihalli C.
Chiaro, Christopher
Hafer, Kelsey T.
Gandhi, Ujjawal H.
Thompson, Jerry T.
van den Heuvel, John P.
Kennett, Mary J.
Hankey, Pamela
Paulson, Robert F.
Prabhu, K. Sandeep
Publication Title: 
Journal of Stem Cells

Cancer stem cells (CSCs) are stem-like tumor populations that are reported to contribute towards tumor growth, maintenance and recurrence after therapy. Hypoxia increases CSC fraction and promotes acquisition of a stem-cell-like state. Cancer stem cells are critically dependant on the hypoxia-inducible factor-1 (HIF-1) for survival, self-renewal, tumor growth and maintenance of their undifferentiated phenotype.

Author(s): 
Bhargav, Hemant
Metri, Kashinath
Raghuram, Nagarathna
Ramarao, Nagendra Hongasandra
Koka, Prasad S.

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