| 1. |
- Diffner, Eva, et al.
(author)
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Expression of VEGF and VEGF Receptors in Childhood Precursor B-cell Acute Lymphoblastic Leukemia Evaluated by Immunohistochemistry
- 2009
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In: Journal of pediatric hematology/oncology (Print). - : Wolters Kluwer. - 1077-4114 .- 1536-3678. ; 31:9, s. 696-701
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Journal article (peer-reviewed)abstract
- Perturbation in the expression and signaling pathways of vascular endothelial growth factor (VEGF) has been linked to pathogenesis of hematologic malignancies. We investigated the expression and clinical importance of VEGF and two of its receptors, VEGFR-1 and VEGFR-2, in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL) by using immunohistochemistry. These angiogenic proteins were expressed in the majority of leukemic bone marrow samples. Notably, pre-B ALL patients had significantly increased expression of VEGFR-1 compared with no expression in the nonmalignant group, indicating a link between VEGFR-1 protein expression and pre-B ALL. These novel findings suggest that VEGFR-1 may have clinical importance in childhood pre-B ALL.
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| 2. |
- Kashyap, Vasundhra, et al.
(author)
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Regulation of Stem Cell Pluripotency and Differentiation Involves a Mutual Regulatory Circuit of the Nanog, OCT4, and SOX2 Pluripotency Transcription Factors With Polycomb Repressive Complexes and Stem Cell microRNAs
- 2009
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In: Stem Cells and Development. - : Mary Ann Liebert. - 1547-3287 .- 1557-8534. ; 18:7, s. 1093-1108
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Research review (peer-reviewed)abstract
- Coordinated transcription factor networks have emerged as the master regulatory mechanisms of stem cell pluripotency and differentiation. Many stem cell-specific transcription factors, including the pluripotency transcription factors, OCT4, NANOG, and SOX2 function in combinatorial complexes to regulate the expression of loci, which are involved in embryonic stem (ES) cell pluripotency and cellular differentiation. This review will address how these pathways form a reciprocal regulatory circuit whereby the equilibrium between stem cell self-renewal, proliferation, and differentiation is in perpetual balance. We will discuss how distinct epigenetic repressive pathways involving polycomb complexes, DNA methylation, and microRNAs cooperate to reduce transcriptional noise and to prevent stochastic and aberrant induction of differentiation. We will provide a brief overview of how these networks cooperate to modulate differentiation along hematopoietic and neuronal lineages. Finally, we will describe how aberrant functioning of components of the stem cell regulatory network may contribute to malignant transformation of adult stem cells and the establishment of a "cancer stem cell" phenotype and thereby underlie multiple types of human malignancies.
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| 3. |
- Marcinkiewicz, Katarzyna, et al.
(author)
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The androgen receptor and stem cell pathways in prostate and bladder cancers (review).
- 2012
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In: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 40:1, s. 5-12
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Journal article (peer-reviewed)abstract
- Bladder cancer is three times more common in men than in women. However, the physiological basis of the male predominance of bladder cancer remains poorly understood. A higher than expected association of prostate and bladder cancers has also been reported which may indicate a common mechanism of carcinogenesis. Consistent with this, androgens and the androgen receptor (AR) play essential roles in prostate carcinogenesis and are believed to play a role in bladder carcinogenesis. There is also evidence implicating cancer stem cells in prostate and bladder cancers. Indeed putative prostate and bladder cancer stem cells share some common molecular features. We highlight key proteins (CD49f, CD133, PTEN, CD44) which are implicated in both prostate and bladder cancers and are enriched in putative prostate and bladder cancer stem cells. We examine published chromatin immuno-precipitation studies analyzing the genome-wide distribution of the AR to identify AR association with, and by inference potential AR-regulation of, these loci. We discuss recent evidence indicating a role for the AR in the splicing of the key urological stem cell protein CD44. We propose a model whereby aberrant AR regulation of these putative stem cell proteins contributes to malignant transformation of prostate and bladder cells. For these reasons we propose that the relationship between androgens and cancer stem cell associated proteins warrants further investigation.
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| 4. |
- Nemeth, Zsuzsanna, et al.
(author)
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Heme oxygenase-1 in macrophages controls prostate cancer progression
- 2015
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:32, s. 33675-33688
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Journal article (peer-reviewed)abstract
- Innate immune cells strongly influence cancer growth and progression via multiple mechanisms including regulation of epithelial to mesenchymal transition (EMT). In this study, we investigated whether expression of the metabolic gene, heme oxygenase-1 (HO-1) in tumor microenvironment imparts significant effects on prostate cancer progression.We showed that HO-1 is expressed in MARCO-positive macrophages in prostate cancer (PCa) xenografts and human prostate cancers. We demonstrated that macrophage specific (LyzM-Cre) conditional deletion of HO-1 suppressed growth of PC3 xenografts in vivo and delayed progression of prostate intraepithelial neoplasia (PIN) in TRAMP mice. However, initiation and progression of cancer xenografts in the presence of macrophages lacking HO-1 resulted in loss of E-cadherin, a known marker of poor prognosis as well as EMT. Application of CO, a product of HO-1 catalysis, increased levels of E-cadherin in the adherens junctions between cancer cells. We further showed that HO-1-driven expression of E-cadherin in cancer cells cultured in the presence of macrophages is dependent on mitochondrial activity of cancer cells.In summary, these data suggest that HO-1-derived CO from tumor-associated macrophages influences, in part, E-cadherin expression and thus tumor initiation and progression.
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| 5. |
- Semenas, Julius, et al.
(author)
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Overcoming drug resistance and treating advanced prostate cancer
- 2012
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In: Current Drug Targets. - : Bentham Science. - 1389-4501 .- 1873-5592. ; 13:10, s. 1308-1323
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Journal article (peer-reviewed)abstract
- Most of the prostate cancers (PCa) in advanced stage will progress to castration-resistant prostate cancer (CRPC). Within CRPC group, 50-70% of the patients will develop bone metastasis in axial and other regions of the skeleton. Once PCa cells spread to the bone, currently, no treatment regimens are available to eradicate the metastasis, and cancer-related death becomes inevitable. In 2012, it is estimated that there will be 28,170 PCa deaths in the United States. Thus, PCa bone metastasis-associated clinical complications and treatment resistance pose major clinical challenges. In this review, we will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa. We will address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis, and will further discuss why prostate cancer cells preferentially metastasize to the bone. Additionally, we will discuss novel roles of several key pathways, including angiogenesis and extracellular matrix remodeling in bone marrow and stem cell niches with their relationship to PCa bone metastasis and poor treatment response. We will evaluate how various chemotherapeutic drugs and radiation therapies may allow aggressive PCa cells to gain advantageous mutations leading to increased survival and rendering the cancer cells to become resistant to treatment. The novel concept relating several key survival and invasion signaling pathways to stem cell niches and treatment resistance will be reviewed. Lastly, we will provide an update of several recently developed novel drug candidates that target metastatic cancer microenvironments or niches, and discuss the advantages and significance provided by such therapeutic approaches in pursuit of overcoming drug resistance and treating advanced PCa.
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