scholarly journals Duality of glucocorticoid action in cancer: tumor-suppressor or oncogene?

2021 ◽  
Author(s):  
Isabel Mayayo-Peralta ◽  
Wilbert Zwart ◽  
Stefan Prekovic
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Transcription Factor ◽  
Lung Function ◽  
Human Biology ◽  
Cancer Type ◽  
Disease Development ◽  
Cancer Tumor ◽  
Molecular Aspects ◽  
Glucocorticoid Action

Glucocorticoid receptor (GR) is a key homeostatic regulator involved in governing immune response, neuro-integration, metabolism and lung function. In conjunction with its pivotal role in human biology, GR action is critically linked to pathology of various disease types, including cancer. While pharmacological activation of GR has been used for treatment of various liquid cancers, its role in solid cancers is less clearly defined and seems to be cancer-type dependent. This review focuses on the molecular aspects of GR biology, spanning the structural and functional basis of response to glucocorticoids, as well as how this transcription factor operates in cancer, including the implications in disease development, progression and drug resistance.

scholarly journals Pea–Fusarium solani Interactions Contributions of a System Toward Understanding Disease Resistance

2008 ◽  
Vol 98 (4) ◽  
pp. 372-379 ◽  
Author(s):  
Lee A. Hadwiger
Keyword(s):  
Immune Response ◽  
Transcription Factor ◽  
Disease Resistance ◽  
Fusarium Solani ◽  
Nonhost Resistance ◽  
Chromatin Conformation ◽  
Resistance Response ◽  
Resistance Components ◽  
Pathogenesis Related ◽  
Molecular Aspects

This mini-review points to the usefulness of the pea–Fusarium solani interaction in researching the biochemical and molecular aspects of the nonhost resistance components of peas. This interaction has been researched to evaluate the resistance roles of the phytoalexin, pisatin, the cuticle barrier, and the activation of the nonhost resistance response. Concurrently, evaluations of associated signaling processes and the tools possessed by the pathogen to contend with host obstacles were included. The properties of some pathogenesis-related genes of pea and their regulation and contribution to resistance are discussed. A proposed action of two biotic elicitors on both chromatin conformation and the architectural transcription factor, HMG A, is presented and includes time lines of events within the host immune response.

Macrophage Flipping from Foe to Friend: A Matter of Interest in Breast Carcinoma Heterogeneity Driving Drug Resistance

2019 ◽  
Vol 19 (3) ◽  
pp. 189-198 ◽  
Author(s):  
Ishita Tandon ◽  
Nilesh Kumar Sharma
Keyword(s):  
Drug Resistance ◽  
Breast Carcinoma ◽  
Tumor Heterogeneity ◽  
Cellular Heterogeneity ◽  
Cancer Type ◽  
Tumor Type ◽  
Cancer Types ◽  
Clinical Drugs ◽  
Molecular Aspects ◽  
Cancer Immunotherapeutic

Tumor heterogeneity within various cancer types including breast carcinoma is pivotal in the manifestations of tumor hallmarks. Tumor heterogeneity is seen as a common landscape where intra-tumoral components including cellular and non-cellular factors create an interface with outside environment that leads to the unique identity of a specific cancer type. Among various contributors to tumor heterogeneity, cellular heterogeneity immensely plays a role in drug resistance and relapse of cancer. Within cellular heterogeneity of tumor, tumor-associated macrophages (TAMs) are the pro-tumor type of immune cells that promote growth, metastasis and drug resistance in breast carcinoma and other cancer types. Revealing the molecular aspects of TAMs can provide a breakthrough to remove therapeutics blockade to existing drugs and this understanding in future will pave the way for a new class of cancer immunotherapeutic. This review addresses current understanding of the role of TAMs in breast carcinoma hallmarks and clarifies the current scenario of pre-clinical drugs directed to tame pro-cancer TAMs.

scholarly journals Role of Small Molecule Targeted Compounds in Cancer: Progress, Opportunities, and Challenges

2021 ◽  
Vol 9 ◽  
Author(s):  
Guoqiang Sun ◽  
Dawei Rong ◽  
Zhouxiao Li ◽  
Guangshun Sun ◽  
Fan Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Drug Resistance ◽  
Targeted Therapy ◽  
Drug Administration ◽  
Small Molecule ◽  
Molecular Targeted Therapy ◽  
Low Cost ◽  
Future Directions ◽  
Clinical Drug

Research on molecular targeted therapy of tumors is booming, and novel targeted therapy drugs are constantly emerging. Small molecule targeted compounds, novel targeted therapy drugs, can be administered orally as tablets among other methods, and do not draw upon genes, causing no immune response. It is easily structurally modified to make it more applicable to clinical needs, and convenient to promote due to low cost. It refers to a hotspot in the research of tumor molecular targeted therapy. In the present study, we review the current Food and Drug Administration (FDA)-approved use of small molecule targeted compounds in tumors, summarize the clinical drug resistance problems and mechanisms facing the use of small molecule targeted compounds, and predict the future directions of the evolving field.

scholarly journals New Insights into the Pleiotropic Drug Resistance Network from Genome-Wide Characterization of the YRR1 Transcription Factor Regulation System

2002 ◽  
Vol 22 (8) ◽  
pp. 2642-2649 ◽  
Author(s):  
Stéphane Le Crom ◽  
Frédéric Devaux ◽  
Philippe Marc ◽  
Xiaoting Zhang ◽  
W. Scott Moye-Rowley ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcription Factor ◽  
Binding Site ◽  
Time Course ◽  
Target Genes ◽  
Regulation System ◽  
Dependent Manner ◽  
Pleiotropic Drug Resistance ◽  
Genome Wide

ABSTRACT Yrr1p is a recently described Zn2Cys6 transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

scholarly journals Dysfunction of Prohibitin 2 Results in Reduced Susceptibility to Multiple Antifungal Drugs via Activation of the Oxidative Stress-Responsive Transcription Factor Pap1 in Fission Yeast

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Qiannan Liu ◽  
Fan Yao ◽  
Guanglie Jiang ◽  
Min Xu ◽  
Si Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Transcription Factor ◽  
Fission Yeast ◽  
Mitochondrial Protein ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Gene Encoding ◽  
Content Type ◽  
Antifungal Drug Resistance

ABSTRACT The fight against resistance to antifungal drugs requires a better understanding of the underlying cellular mechanisms. In order to gain insight into the mechanisms leading to antifungal drug resistance, we performed a genetic screen on a model organism, Schizosaccharomyces pombe, to identify genes whose overexpression caused resistance to antifungal drugs, including clotrimazole and terbinafine. We identified the phb2+ gene, encoding a highly conserved mitochondrial protein, prohibitin (Phb2), as a novel determinant of reduced susceptibility to multiple antifungal drugs. Unexpectedly, deletion of the phb2+ gene also exhibited antifungal drug resistance. Overexpression of the phb2+ gene failed to cause drug resistance when the pap1+ gene, encoding an oxidative stress-responsive transcription factor, was deleted. Furthermore, pap1+ mRNA expression was significantly increased when the phb2+ gene was overexpressed or deleted. Importantly, either overexpression or deletion of the phb2+ gene stimulated the synthesis of NO and reactive oxygen species (ROS), as measured by the cell-permeant fluorescent NO probe DAF-FM DA (4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate) and the ROS probe DCFH-DA (2′,7′-dichlorodihydrofluorescein diacetate), respectively. Taken together, these results suggest that Phb2 dysfunction results in reduced susceptibility to multiple antifungal drugs by increasing NO and ROS synthesis due to dysfunctional mitochondria, thereby activating the transcription factor Pap1 in fission yeast.

scholarly journals The Hypoxia-Inducible Transcription Factor ZNF395 Is Controlled by IĸB Kinase-Signaling and Activates Genes Involved in the Innate Immune Response and Cancer

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74911 ◽  
Author(s):  
Darko Jordanovski ◽  
Christine Herwartz ◽  
Anna Pawlowski ◽  
Stefanie Taute ◽  
Peter Frommolt ◽  
...  
Keyword(s):  
Immune Response ◽  
Transcription Factor ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Kinase Signaling
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