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Article ; Online: Introduction at the special issue on implications of cancer stem/progenitor cell concepts in molecular oncology and novel targeted therapies.

Mimeault, Murielle / Batra, Surinder K

2014 Volume 39, Page(s) 1–2

MeSH term(s)	Humans ; Molecular Targeted Therapy ; Neoplasms/therapy ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/transplantation ; Pathology, Molecular
Language	English
Publishing date	2014-10
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	197640-0
ISSN	1872-9452 ; 0098-2997
ISSN (online)	1872-9452
ISSN	0098-2997
DOI	10.1016/j.mam.2013.09.001
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Article ; Online: Molecular biomarkers of cancer stem/progenitor cells associated with progression, metastases, and treatment resistance of aggressive cancers.

Mimeault, Murielle / Batra, Surinder K

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2013 Volume 23, Issue 2, Page(s) 234–254

Abstract: The validation of novel diagnostic, prognostic, and predictive biomarkers and therapeutic targets in tumor cells is of critical importance for optimizing the choice and efficacy of personalized therapies. Importantly, recent advances have led to the ... ...

Abstract	The validation of novel diagnostic, prognostic, and predictive biomarkers and therapeutic targets in tumor cells is of critical importance for optimizing the choice and efficacy of personalized therapies. Importantly, recent advances have led to the identification of gene-expression signatures in cancer cells, including cancer stem/progenitor cells, in the primary tumors, exosomes, circulating tumor cells (CTC), and disseminated cancer cells at distant metastatic sites. The gene-expression signatures may help to improve the accuracy of diagnosis and predict the therapeutic responses and overall survival of patients with cancer. Potential biomarkers in cancer cells include stem cell-like markers [CD133, aldehyde dehydrogenase (ALDH), CD44, and CD24], growth factors, and their cognate receptors [epidermal growth factor receptor (EGFR), EGFRvIII, and HER2], molecules associated with epithelial-mesenchymal transition (EMT; vimentin, N-cadherin, snail, twist, and Zeb1), regulators of altered metabolism (phosphatidylinositol-3' kinase/Akt/mTOR), and drug resistance (multidrug transporters and macrophage inhibitory cytokine-1). Moreover, different pluripotency-associated transcription factors (Oct3/4, Nanog, Sox2, and Myc) and microRNAs that are involved in the epigenetic reprogramming and acquisition of stem cell-like properties by cancer cells during cancer progression may also be exploited as molecular biomarkers to predict the risk of metastases, systemic treatment resistance, and disease relapse of patients with cancer.
MeSH term(s)	Animals ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Disease Progression ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2013-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-13-0785
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Article ; Online: Altered gene products involved in the malignant reprogramming of cancer stem/progenitor cells and multitargeted therapies.

Mimeault, Murielle / Batra, Surinder K

Molecular aspects of medicine

2013 Volume 39, Page(s) 3–32

Abstract: Recent studies in the field of cancer stem cells have revealed that the alterations in key gene products involved in the epithelial-mesenchymal transition (EMT) program, altered metabolic pathways such as enhanced glycolysis, lipogenesis and/or autophagy ...

Abstract	Recent studies in the field of cancer stem cells have revealed that the alterations in key gene products involved in the epithelial-mesenchymal transition (EMT) program, altered metabolic pathways such as enhanced glycolysis, lipogenesis and/or autophagy and treatment resistance may occur in cancer stem/progenitor cells and their progenies during cancer progression. Particularly, the sustained activation of diverse developmental cascades such as hedgehog, epidermal growth factor receptor (EGFR), Wnt/β-catenin, Notch, transforming growth factor-β (TGF-β)/TGF-βR receptors and/or stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) can play critical functions for high self-renewal potential, survival, invasion and metastases of cancer stem/progenitor cells and their progenies. It has also been observed that cancer cells may be reprogrammed to re-express different pluripotency-associated stem cell-like markers such as Myc, Oct-3/4, Nanog and Sox-2 along the EMT process and under stressful and hypoxic conditions. Moreover, the enhanced expression and/or activities of some drug resistance-associated molecules such as Bcl-2, Akt/molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), hypoxia-inducible factors (HIFs), macrophage inhibitory cytokine-1 (MIC-1) and ATP-binding cassette (ABC) multidrug transporters frequently occur in cancer cells during cancer progression and metastases. These molecular events may cooperate for the survival and acquisition of a more aggressive and migratory behavior by cancer stem/progenitor cells and their progenies during cancer transition to metastatic and recurrent disease states. Of therapeutic interest, these altered gene products may also be exploited as molecular biomarkers and therapeutic targets to develop novel multitargeted strategies for improving current cancer therapies and preventing disease relapse.
MeSH term(s)	Animals ; Cellular Reprogramming ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Humans ; Molecular Targeted Therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplastic Stem Cells/metabolism ; Signal Transduction
Language	English
Publishing date	2013-08-29
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	197640-0
ISSN	1872-9452 ; 0098-2997
ISSN (online)	1872-9452
ISSN	0098-2997
DOI	10.1016/j.mam.2013.08.001
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Article ; Online: Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells.

Mimeault, Murielle / Batra, Surinder K

Journal of cellular and molecular medicine

2013 Volume 17, Issue 1, Page(s) 30–54

Abstract: Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient ... ...

Abstract	Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3'-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Apoptosis ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Transformation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia/drug therapy ; Hypoxia/genetics ; Hypoxia/metabolism ; Hypoxia/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Antineoplastic Agents ; Basic Helix-Loop-Helix Transcription Factors ; HIF1A protein, human ; Hypoxia-Inducible Factor 1, alpha Subunit ; Intercellular Signaling Peptides and Proteins ; Transcription Factors ; endothelial PAS domain-containing protein 1 (1B37H0967P)
Language	English
Publishing date	2013-01-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.12004
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Zs.A 5752: Show issues

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Article: Development of animal models underlining mechanistic connections between prostate inflammation and cancer.

Mimeault, Murielle / Batra, Surinder K

World journal of clinical oncology

2012 Volume 4, Issue 1, Page(s) 4–13

Abstract: The characterization of animal models has indicated that the genetic, dietary and environmental factors and hormonal imbalance may influence the risk to develop prostate inflammatory lesions and prostate cancer (PC) confirming human epidemiologic data. ... ...

Abstract	The characterization of animal models has indicated that the genetic, dietary and environmental factors and hormonal imbalance may influence the risk to develop prostate inflammatory lesions and prostate cancer (PC) confirming human epidemiologic data. It is now established that the prostate inflammatory response typically results in major changes in the local microenvironment of epithelial cells of the prostate gland, including an intense stromal remodeling, activation of fibroblasts, infiltration of immune cells such as mast cells, macrophages and B and T lymphocytes and collagen deposition. The immune cells recruited at prostate inflammatory lesions and myofibroblasts may contribute to the release of numerous pro-inflammatory cytokines and chemokines that in turn can promote the oxidative stress, genomic instability and proliferation of epithelial cells. The accumulation of additional genetic and/or epigenetic alterations in prostatic stem/progenitor cells may subsequently culminate to their malignant transformation and PC initiation and progression and more particularly with advancing age. The potential mechanistic relationships between the molecular events associated with the persistent inflammatory response and prostate carcinogenesis have important implications for optimizing the current therapies against different prostatic disorders and PCs.
Language	English
Publishing date	2012-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2587357-X
ISSN	2218-4333
ISSN	2218-4333
DOI	10.5306/wjco.v4.i1.4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials.

Mimeault, Murielle / Batra, Surinder K

Drug discovery today

2012 Volume 18, Issue 3-4, Page(s) 128–140

Abstract: The in vivo zebrafish models have recently attracted great attention in molecular oncology to investigate multiple genetic alterations associated with the development of human cancers and validate novel anticancer drug targets. Particularly, the ... ...

Abstract	The in vivo zebrafish models have recently attracted great attention in molecular oncology to investigate multiple genetic alterations associated with the development of human cancers and validate novel anticancer drug targets. Particularly, the transparent zebrafish models can be used as a xenotransplantation system to rapidly assess the tumorigenicity and metastatic behavior of cancer stem and/or progenitor cells and their progenies. Moreover, the zebrafish models have emerged as powerful tools for an in vivo testing of novel anticancer agents and nanomaterials for counteracting tumor formation and metastases and improving the efficacy of current radiation and chemotherapeutic treatments against aggressive, metastatic and lethal cancers.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Disease Models, Animal ; Humans ; Nanostructures ; Neoplasms/metabolism ; Zebrafish
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2012-08-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2012.08.002
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Zs.A 4725: Show issues

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Article: New advances on structural and biological functions of ceramide in apoptotic/necrotic cell death and cancer.

Mimeault, Murielle

FEBS letters

2002 Volume 530, Issue 1-3, Page(s) 9–16

Abstract: Recent data on the cellular ceramide functions and its involvement in the apoptotic/necrotic cell death as well as its anticarcinogenic properties are presented. The emphasis is on the connections between the ceramide and caspase signaling pathways ... ...

Abstract	Recent data on the cellular ceramide functions and its involvement in the apoptotic/necrotic cell death as well as its anticarcinogenic properties are presented. The emphasis is on the connections between the ceramide and caspase signaling pathways during the apoptotic cell death process. Notably, the experimental strategies and pharmacological tools used for establishment of the role of ceramide in triggering cell death are described. Moreover, the importance of a compartmentation of endogenous ceramide within the plasma membrane microdomains, lysosomes and mitochondria is discussed. Information on the deregulated functions of ceramide and caspase signaling pathways in several metastatic cancer types is also presented.
MeSH term(s)	Apoptosis/physiology ; Ceramides/chemistry ; Ceramides/physiology ; Necrosis ; Neoplasms/pathology ; Nitric Oxide/biosynthesis
Chemical Substances	Ceramides ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2002-07-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/s0014-5793(02)03432-4
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Article: Great promise of tissue-resident adult stem/progenitor cells in transplantation and cancer therapies.

Mimeault, Murielle / Batra, Surinder K

Advances in experimental medicine and biology

2012 Volume 741, Page(s) 171–186

Abstract: Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and ... ...

Abstract	Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed with a high self-renewal ability and multilineage differentiation potential, which are able to regenerate all the mature cells in the tissues from their origin, offers great promise in replacing non-functioning or lost cells and regenerating diseased and damaged tissues. The presence of a small subpopulation of adult stem/progenitor cells in most tissues and organs provides the possibility of stimulating their in vivo differentiation, or of using their ex vivo expanded progenies for cell-replacement and gene therapies with multiple applications in humans without a high-risk of graft rejection and major side effects. Among the diseases that could be treated by adult stem cell-based therapies are hematopoietic and immune disorders, multiple degenerative disorders such as Parkinson's and Alzheimer's diseases, Types 1 and 2 diabetes mellitus as well as skin, eye, liver, lung, tooth and cardiovascular disorders. In addition, a combination of the current cancer treatments with an adjuvant treatment consisting of an autologous or allogeneic adult stem/progenitor cell transplantation also represents a promising strategy for treating and even curing diverse aggressive, metastatic, recurrent and lethal cancers. In this chapter, we reviewed the most recent advancements on the characterization of phenotypic and functional properties of adult stem/progenitor cell types found in bone marrow, heart, brain and other tissues and discussed their therapeutic implications in the stem cell-based transplantation therapy.
MeSH term(s)	Adult Stem Cells/cytology ; Adult Stem Cells/physiology ; Cell- and Tissue-Based Therapy/methods ; Humans ; Neoplasms/pathology ; Neoplasms/therapy ; Stem Cell Transplantation/methods
Language	English
Publishing date	2012-03-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-1-4614-2098-9_12
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas.

Mimeault, Murielle / Batra, Surinder K

World journal of clinical oncology

2012 Volume 3, Issue 3, Page(s) 32–42

Abstract: Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of ...

Abstract	Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cell-based therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition (EMT)-associated molecules, including phosphatidylinositol 3'-kinase (PI3K)/Akt/ molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.
Language	English
Publishing date	2012-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2587357-X
ISSN	2218-4333 ; 2218-4333
ISSN (online)	2218-4333
ISSN	2218-4333
DOI	10.5306/wjco.v3.i3.32
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Article ; Online: Development of animal models underlining mechanistic connections between prostate inflammation and cancer

Murielle Mimeault / Surinder K Batra

World Journal of Clinical Oncology, Vol 4, Iss 1, Pp 4-

2013 Volume 13

Abstract	The characterization of animal models has indicated that the genetic, dietary and environmental factors and hormonal imbalance may influence the risk to develop prostate inflammatory lesions and prostate cancer (PC) confirming human epidemiologic data. It is now established that the prostate inflammatory response typically results in major changes in the local microenvironment of epithelial cells of the prostate gland, including an intense stromal remodeling, activation of fibroblasts, infiltration of immune cells such as mast cells, macrophages and B and T lymphocytes and collagen deposition. The immune cells recruited at prostate inflammatory lesions and myofibroblasts may contribute to the release of numerous pro-inflammatory cytokines and chemokines that in turn can promote the oxidative stress, genomic instability and proliferation of epithelial cells. The accumulation of additional genetic and/or epigenetic alterations in prostatic stem/progenitor cells may subsequently culminate to their malignant transformation and PC initiation and progression and more particularly with advancing age. The potential mechanistic relationships between the molecular events associated with the persistent inflammatory response and prostate carcinogenesis have important implications for optimizing the current therapies against different prostatic disorders and PCs.
Keywords	Animal models ; Prostate inflammation ; Tumor microenvironment ; Stromal remodeling ; Prostate cancer ; Therapies ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Baishideng Publishing Group Co., Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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