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Article ; Online: Pleiotropic endophenotypic and phenotype effects of GABAergic neurosteroid synthesis deficiency in posttraumatic stress disorder.

Rasmusson, Ann M / Novikov, Olga / Brown, Kayla D / Pinna, Graziano / Pineles, Suzanne L

Current opinion in endocrine and metabolic research

2022 Volume 25

Abstract: PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at ... ...

Abstract	PTSD is associated with deficits in synthesis of progesterone metabolites such as allopregnanolone and pregnanolone that potently facilitate gamma-amino-butyric acid (GABA) effects at GABA
Language	English
Publishing date	2022-05-28
Publishing country	England
Document type	Journal Article
ISSN	2451-9650
ISSN (online)	2451-9650
DOI	10.1016/j.coemr.2022.100359
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Article ; Online: How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression.

Wang, Zhongyan / Snyder, Megan / Kenison, Jessica E / Yang, Kangkang / Lara, Brian / Lydell, Emily / Bennani, Kawtar / Novikov, Olga / Federico, Anthony / Monti, Stefano / Sherr, David H

International journal of molecular sciences

2020 Volume 22, Issue 1

Abstract: For decades, the aryl hydrocarbon receptor (AHR) was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had ... ...

Abstract	For decades, the aryl hydrocarbon receptor (AHR) was studied for its role in environmental chemical toxicity i.e., as a quirk of nature and a mediator of unintended consequences of human pollution. During that period, it was not certain that the AHR had a "normal" physiological function. However, the ongoing accumulation of data from an ever-expanding variety of studies on cancer, cancer immunity, autoimmunity, organ development, and other areas bears witness to a staggering array of AHR-controlled normal and pathological activities. The objective of this review is to discuss how the AHR has gone from a likely contributor to genotoxic environmental carcinogen-induced cancer to a master regulator of malignant cell progression and cancer aggression. Particular focus is placed on the association between AHR activity and poor cancer outcomes, feedback loops that control chronic AHR activity in cancer, and the role of chronically active AHR in driving cancer cell invasion, migration, cancer stem cell characteristics, and survival.
MeSH term(s)	Animals ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism
Chemical Substances	Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2020-12-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22010387
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Article ; Online: Towards Resolving the Pro- and Anti-Tumor Effects of the Aryl Hydrocarbon Receptor.

Narasimhan, Supraja / Stanford Zulick, Elizabeth / Novikov, Olga / Parks, Ashley J / Schlezinger, Jennifer J / Wang, Zhongyan / Laroche, Fabrice / Feng, Hui / Mulas, Francesca / Monti, Stefano / Sherr, David H

International journal of molecular sciences

2018 Volume 19, Issue 5

Abstract: We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose ... ...

Abstract	We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose tumor aggression. Resolving this apparent contradiction is critical to the design of AHR-targeted cancer therapeutics. Molecular (siRNA, shRNA, AHR repressor, CRISPR-Cas9) and pharmacological (AHR inhibitors) approaches were used to confirm the hypothesis that AHR inhibition reduces human cancer cell invasion (irregular colony growth in 3D Matrigel cultures and Boyden chambers), migration (scratch wound assay) and metastasis (human cancer cell xenografts in zebrafish). Furthermore, these assays were used for a head-to-head comparison between AHR antagonists and agonists. AHR inhibition or knockdown/knockout consistently reduced human ER
MeSH term(s)	Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement/drug effects ; Female ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Neoplasm Invasiveness/genetics ; Neoplasm Invasiveness/pathology ; Neoplasm Invasiveness/prevention & control ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Receptors, Aryl Hydrocarbon/agonists ; Receptors, Aryl Hydrocarbon/antagonists & inhibitors ; Receptors, Aryl Hydrocarbon/genetics ; Zebrafish
Chemical Substances	Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2018-05-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms19051388
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Article ; Online: An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells.

Novikov, Olga / Wang, Zhongyan / Stanford, Elizabeth A / Parks, Ashley J / Ramirez-Cardenas, Alejandra / Landesman, Esther / Laklouk, Israa / Sarita-Reyes, Carmen / Gusenleitner, Daniel / Li, Amy / Monti, Stefano / Manteiga, Sara / Lee, Kyongbum / Sherr, David H

Molecular pharmacology

2016 Volume 90, Issue 5, Page(s) 674–688

Abstract: The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are ... ...

Abstract	The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER
MeSH term(s)	Cell Line, Tumor ; Cell Movement ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Kynurenine/metabolism ; Ligands ; Models, Biological ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptor, ErbB-2/metabolism ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/metabolism ; Triple Negative Breast Neoplasms/pathology ; Tryptophan/metabolism ; Tryptophan Oxygenase/genetics ; Tryptophan Oxygenase/metabolism ; Xanthurenates/metabolism
Chemical Substances	Ligands ; RNA, Messenger ; Receptors, Aryl Hydrocarbon ; Receptors, Estrogen ; Receptors, Progesterone ; Xanthurenates ; Kynurenine (343-65-7) ; xanthurenic acid (58LAB1BG8J) ; Tryptophan (8DUH1N11BX) ; Tryptophan Oxygenase (EC 1.13.11.11) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2016-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.116.105361
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Article ; Online: Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis.

Stanford, Elizabeth A / Ramirez-Cardenas, Alejandra / Wang, Zhongyan / Novikov, Olga / Alamoud, Khalid / Koutrakis, Petros / Mizgerd, Joseph P / Genco, Caroline A / Kukuruzinska, Maria / Monti, Stefano / Bais, Manish V / Sherr, David H

Molecular cancer research : MCR

2016 Volume 14, Issue 8, Page(s) 696–706

Abstract: Unlabelled: Over 45,000 new cases of oral and pharyngeal cancers are diagnosed and account for over 8,000 deaths a year in the United States. An environmental chemical receptor, the aryl hydrocarbon receptor (AhR), has previously been implicated in oral ...

Abstract	Unlabelled: Over 45,000 new cases of oral and pharyngeal cancers are diagnosed and account for over 8,000 deaths a year in the United States. An environmental chemical receptor, the aryl hydrocarbon receptor (AhR), has previously been implicated in oral squamous cell carcinoma (OSCC) initiation as well as in normal tissue-specific stem cell self-renewal. These previous studies inspired the hypothesis that the AhR plays a role in both the acquisition and progression of OSCC, as well as in the formation and maintenance of cancer stem-like cells. To test this hypothesis, AhR activity in two oral squamous cell lines was modulated with AhR prototypic, environmental and bacterial AhR ligands, AhR-specific inhibitors, and phenotypic, genomic and functional characteristics were evaluated. The data demonstrate that: (i) primary OSCC tissue expresses elevated levels of nuclear AhR as compared with normal tissue, (ii) AhR mRNA expression is upregulated in 320 primary OSCCs, (iii) AhR hyperactivation with several ligands, including environmental and bacterial ligands, significantly increases AhR activity, ALDH1 activity, and accelerates cell migration, (iv) AhR inhibition blocks the rapid migration of OSCC cells and reduces cell chemoresistance, (v) AhR knockdown inhibits tumorsphere formation in low adherence conditions, and (vi) AhR knockdown inhibits tumor growth and increases overall survival in vivo These data demonstrate that the AhR plays an important role in development and progression of OSCC, and specifically cancer stem-like cells. Prototypic, environmental, and bacterial AhR ligands may exacerbate OSCC by enhancing expression of these properties. Implications: This study, for the first time, demonstrates the ability of diverse AhR ligands to regulate AhR activity in oral squamous cell carcinoma cells, as well as regulate several important characteristics of oral cancer stem cells, in vivo and in vitro Mol Cancer Res; 14(8); 696-706. ©2016 AACR.
MeSH term(s)	Animals ; Carcinogenesis ; Carcinoma, Squamous Cell/genetics ; Carcinoma, Squamous Cell/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease Models, Animal ; Female ; Humans ; Ligands ; Mice ; Mice, Nude ; Mouth Neoplasms/genetics ; Mouth Neoplasms/pathology ; Receptors, Aryl Hydrocarbon/metabolism ; Signal Transduction ; Transfection
Chemical Substances	Ligands ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2016-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-16-0069
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Article ; Online: The role of the aryl hydrocarbon receptor in the development of cells with the molecular and functional characteristics of cancer stem-like cells.

Stanford, Elizabeth A / Wang, Zhongyan / Novikov, Olga / Mulas, Francesca / Landesman-Bollag, Esther / Monti, Stefano / Smith, Brenden W / Seldin, David C / Murphy, George J / Sherr, David H

BMC biology

2016 Volume 14, Page(s) 20

Abstract: Background: Self-renewing, chemoresistant breast cancer stem cells are believed to contribute significantly to cancer invasion, migration and patient relapse. Therefore, the identification of signaling pathways that regulate the acquisition of stem-like ...

Abstract	Background: Self-renewing, chemoresistant breast cancer stem cells are believed to contribute significantly to cancer invasion, migration and patient relapse. Therefore, the identification of signaling pathways that regulate the acquisition of stem-like qualities is an important step towards understanding why patients relapse and towards development of novel therapeutics that specifically target cancer stem cell vulnerabilities. Recent studies identified a role for the aryl hydrocarbon receptor (AHR), an environmental carcinogen receptor implicated in cancer initiation, in normal tissue-specific stem cell self-renewal. These studies inspired the hypothesis that the AHR plays a role in the acquisition of cancer stem cell-like qualities. Results: To test this hypothesis, AHR activity in Hs578T triple negative and SUM149 inflammatory breast cancer cells were modulated with AHR ligands, shRNA or AHR-specific inhibitors, and phenotypic, genomic and functional stem cell-associated characteristics were evaluated. The data demonstrate that (1) ALDH(high) cells express elevated levels of Ahr and Cyp1b1 and Cyp1a1, AHR-driven genes, (2) AHR knockdown reduces ALDH activity by 80%, (3) AHR hyper-activation with several ligands, including environmental ligands, significantly increases ALDH1 activity, expression of stem cell- and invasion/migration-associated genes, and accelerates cell migration, (4) a significant correlation between Ahr or Cyp1b1 expression (as a surrogate marker for AHR activity) and expression of stem cell- and invasion/migration-associated gene sets is seen with genomic data obtained from 79 human breast cancer cell lines and over 1,850 primary human breast cancers, (5) the AHR interacts directly with Sox2, a master regulator of self-renewal; AHR ligands increase this interaction and nuclear SOX2 translocation, (6) AHR knockdown inhibits tumorsphere formation in low adherence conditions, (7) AHR inhibition blocks the rapid migration of ALDH(high) cells and reduces ALDH(high) cell chemoresistance, (8) ALDH(high) cells are highly efficient at initiating tumors in orthotopic xenografts, and (9) AHR knockdown inhibits tumor initiation and reduces tumor Aldh1a1, Sox2, and Cyp1b1 expression in vivo. Conclusions: These data suggest that the AHR plays an important role in development of cells with cancer stem cell-like qualities and that environmental AHR ligands may exacerbate breast cancer by enhancing expression of these properties.
MeSH term(s)	Breast/metabolism ; Breast/pathology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Receptors, Aryl Hydrocarbon/genetics ; Receptors, Aryl Hydrocarbon/metabolism
Chemical Substances	Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2016-03-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2133020-7
ISSN	1741-7007 ; 1741-7007
ISSN (online)	1741-7007
ISSN	1741-7007
DOI	10.1186/s12915-016-0240-y
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Article ; Online: In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo.

Parks, Ashley J / Pollastri, Michael P / Hahn, Mark E / Stanford, Elizabeth A / Novikov, Olga / Franks, Diana G / Haigh, Sarah E / Narasimhan, Supraja / Ashton, Trent D / Hopper, Timothy G / Kozakov, Dmytro / Beglov, Dimitri / Vajda, Sandor / Schlezinger, Jennifer J / Sherr, David H

Molecular pharmacology

2014 Volume 86, Issue 5, Page(s) 593–608

Abstract: The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of ... ...

Abstract	The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of targeted therapeutics. Here, ligand shape-based virtual modeling techniques were used to identify novel AHR ligands on the basis of previously identified chemotypes. Four structurally unique compounds were identified. One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (CB7993113), was further tested for its ability to block three AHR-dependent biologic activities: triple-negative breast cancer cell invasion or migration in vitro and AHR ligand-induced bone marrow toxicity in vivo. CB7993113 directly bound both murine and human AHR and inhibited polycyclic aromatic hydrocarbon (PAH)- and TCDD-induced reporter activity by 75% and 90% respectively. A novel homology model, comprehensive agonist and inhibitor titration experiments, and AHR localization studies were consistent with competitive antagonism and blockade of nuclear translocation as the primary mechanism of action. CB7993113 (IC50 3.3 × 10(-7) M) effectively reduced invasion of human breast cancer cells in three-dimensional cultures and blocked tumor cell migration in two-dimensional cultures without significantly affecting cell viability or proliferation. Finally, CB7993113 effectively inhibited the bone marrow ablative effects of 7,12-dimethylbenz[a]anthracene in vivo, demonstrating drug absorption and tissue distribution leading to pharmacological efficacy. These experiments suggest that AHR antagonists such as CB7993113 may represent a new class of targeted therapeutics for immunomodulation and/or cancer therapy.
MeSH term(s)	Animals ; Biological Factors/pharmacology ; Bone Marrow Cells/drug effects ; COS Cells ; Cell Line ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Chlorocebus aethiops ; Humans ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Aryl Hydrocarbon/antagonists & inhibitors ; Stromal Cells/drug effects ; Triple Negative Breast Neoplasms/drug therapy
Chemical Substances	Biological Factors ; Ligands ; Receptors, Aryl Hydrocarbon
Language	English
Publishing date	2014-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.114.093369
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 525: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Pleiotropic endophenotypic and phenotype effects of GABAergic neurosteroid synthesis deficiency in posttraumatic stress disorder.

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Article ; Online: How the AHR Became Important in Cancer: The Role of Chronically Active AHR in Cancer Aggression.

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Article ; Online: Towards Resolving the Pro- and Anti-Tumor Effects of the Aryl Hydrocarbon Receptor.

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Article ; Online: An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells.

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Article ; Online: Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis.

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Article ; Online: The role of the aryl hydrocarbon receptor in the development of cells with the molecular and functional characteristics of cancer stem-like cells.

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Article ; Online: In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo.

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In stock of ZB MED Cologne/Königswinter

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