Aberrant Expression and Function of Retinoid Receptors in Cancer

1999 ◽  
pp. 323-343 ◽  
Author(s):  
X.-C. Xu ◽  
R. Lotan
Keyword(s):  
Aberrant Expression ◽  
Retinoid Receptors ◽  
And Function

scholarly journals Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402

Cell Research ◽  
2004 ◽  
Vol 14 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Dong Hong ZHAO ◽  
Jian Jun HONG ◽  
Shi Ying GUO ◽  
Run Lin YANG ◽  
Jun YUAN ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Aberrant Expression ◽  
Hepatocellular Carcinoma Cell Line ◽  
Hepatocellular Carcinoma Cell ◽  
And Function

scholarly journals DNMT3b-mediated methylation of ZSWIM3 enhances inflammation in alcohol-induced liver injury via regulating TRAF2-mediated NF-κB pathway

2020 ◽  
Vol 134 (14) ◽  
pp. 1935-1956 ◽  
Author(s):  
Hai-Di Li ◽  
Xin Chen ◽  
Jie-Jie Xu ◽  
Xiao-Sa Du ◽  
Yang Yang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Zinc Finger ◽  
Inflammatory Responses ◽  
Tumor Necrosis Factor Receptor ◽  
Dna Methyltransferases ◽  
Aberrant Expression ◽  
Ethanol Feeding ◽  
And Function

Abstract The regulation of macrophages during inflammatory responses is a crucial process in alcoholic liver disease (ALD) and aberrant macrophage DNA methylation is associated with inflammation. Our preliminary screening results of macrophage methylation in the present study demonstrated the zinc finger SWI2/SNF2 and MuDR (SWIM)-domain containing 3 (ZSWIM3) were hypermethylated in the 5′ untranslated region (5′-UTR) region. ZSWIM3, a novel zinc finger-chelate domain of SWIM, is predicted to function in DNA-binding and protein-binding interactions. Its expression was found to be consistently decreased in macrophages isolated from livers of ethyl alcohol (EtOH)-fed mice and in EtOH+lipopolysaccharide (LPS)-induced RAW264.7 cells. Over-expression of ZSWIM3 was found to attenuate chronic+binge ethanol feeding-induced liver injury and inhibit inflammatory responses in vivo. Enforced expression of ZSWIM3 in vitro was also found to have anti-inflammatory effects. Aberrant expression of ZSWIM3 in alcohol-induced liver injury (ALI) was found to be associated with hypermethylation. Analysis of CpG prediction indicated the presence of two methylated sites in the ZSWIM3 promoter region and methylation inhibitor and DNA methyltransferases (DNMTs)-siRNA transfection were found to restore down-regulated ZSWIM3. Chromatin immunoprecipitation (ChIP) assay and molecular docking affirmed the role of DNMT 3b (DNMT3b) as a principal regulator of ZSWIM3 expression. Mechanistically, ZSWIM3 might affect inflammation by binding with tumor necrosis factor receptor-associated factor 2 (TRAF2), which further mediates the activation of the nuclear transcription factor κB (NF-κB) pathway. The present study, therefore, provides detailed insights into the possible structure and function of ZSWIM3 and thus, contributes new substantial research in the elucidation of the pathogenesis of ALI.

scholarly journals HDAC Inhibitors Exert Anti-Myeloma Effects through Multiple Modes of Action

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 475 ◽  
Author(s):  
Yoichi Imai ◽  
Mitsuhito Hirano ◽  
Masayuki Kobayashi ◽  
Muneyoshi Futami ◽  
Arinobu Tojo
Keyword(s):  
Proteasome Inhibitor ◽  
Biological Effects ◽  
Hdac Inhibitors ◽  
Therapeutic Strategies ◽  
Aberrant Expression ◽  
Cytotoxic Effects ◽  
Multiple Modes ◽  
Chaperone Function ◽  
Modes Of Action ◽  
And Function

HDACs are critical regulators of gene expression that function through histone modification. Non-histone proteins and histones are targeted by these proteins and the inhibition of HDACs results in various biological effects. Moreover, the aberrant expression and function of these proteins is thought to be related to the pathogenesis of multiple myeloma (MM) and several inhibitors have been introduced or clinically tested. Panobinostat, a pan-HDAC inhibitor, in combination with a proteasome inhibitor and dexamethasone has improved survival in relapsing/refractory MM patients. We revealed that panobinostat inhibits MM cell growth by degrading the protein PPP3CA, a catalytic subunit of calcineurin. This degradation was suggested to be mediated by suppression of the chaperone function of HSP90 due to HDAC6 inhibition. Cytotoxicity due to the epigenetic regulation of tumor-associated genes by HDAC inhibitors has also been reported. In addition, HDAC6 inhibition enhances tumor immunity and has been suggested to strengthen the cytotoxic effects of therapeutic antibodies against myeloma. Furthermore, therapeutic strategies to enhance the anti-myeloma effects of HDAC inhibitors through the addition of other agents has been intensely evaluated. Thus, the treatment of patients with MM using HDAC inhibitors is promising as these drugs exert their effects through multiple modes of action.

GDF-15: A Multifunctional Modulator and Potential Therapeutic Target in Cancer

2019 ◽  
Vol 25 (6) ◽  
pp. 654-662 ◽  
Author(s):  
Lei Fang ◽  
Fengzhou Li ◽  
Chundong Gu
Keyword(s):  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Immune Escape ◽  
Cell Formation ◽  
Transforming Growth Factor Β ◽  
Response To Therapy ◽  
Potential Therapeutic Target ◽  
Aberrant Expression ◽  
Basic Functions ◽  
And Function

Various pathological processes are associated with the aberrant expression and function of cytokines, especially those belonging to the transforming growth factor-β (TGF-β) family. Nevertheless, the functions of members of the TGF-β family in cancer progression and therapy are still uncertain. Growth differentiation factor- 15, which exists in intracellular and extracellular forms, is classified as a divergent member of the TGF-β superfamily. It has been indicated that GDF-15 is also connected to the evolution of cancer both positively and negatively depending upon the cellular state and environment. Under normal physiological conditions, GDF-15 inhibits early tumour promotion. However, its abnormal expression in advanced cancers causes proliferation, invasion, metastasis, cancer stem cell formation, immune escape and a reduced response to therapy. As a clinical indicator, GDF-15 can be used as a tool for the diagnosis and therapy of an extensive scope of cancers. Although some basic functions of GDF-15 are noncontroversial, their mechanisms remain unclear and complicated at the molecular level. Therefore, GDF-15 needs to be further explored and reviewed.

scholarly journals Fusogen-mediated neuron−neuron fusion disrupts neural circuit connectivity and alters animal behavior

2020 ◽  
Vol 117 (37) ◽  
pp. 23054-23065
Author(s):  
Rosina Giordano-Santini ◽  
Eva Kaulich ◽  
Kate M. Galbraith ◽  
Fiona K. Ritchie ◽  
Wei Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fusion ◽  
Animal Behavior ◽  
Neural Circuit ◽  
Neurological Diseases ◽  
Aberrant Expression ◽  
Neuronal Fate ◽  
Behavioral Impairments ◽  
And Function ◽  
Cell Cell

The 100-y-old neuron doctrine from Ramón y Cajal states that neurons are individual cells, rejecting the process of cell−cell fusion in the normal development and function of the nervous system. However, fusogens—specialized molecules essential and sufficient for the fusion of cells—are expressed in the nervous system of different species under conditions of viral infection, stress, or disease. Despite these findings, whether the expression of fusogens in neurons leads to cell−cell fusion, and, if so, whether this affects neuronal fate, function, and animal behavior, has not been explored. Here, using Caenorhabditis elegans chemosensory neurons as a model system, we provide proof-of-principle that aberrant expression of fusogens in neurons results in neuron−neuron fusion and behavioral impairments. We demonstrate that fusion between chemoattractive neurons does not affect the response to odorants, whereas fusion between chemoattractive and chemorepulsive neurons compromises chemosensation. Moreover, we provide evidence that fused neurons are viable and retain their original specific neuronal fate markers. Finally, analysis of calcium transients reveals that fused neurons become electrically coupled, thereby compromising neural circuit connectivity. Thus, we propose that aberrant expression of fusogens in the nervous system disrupts neuronal individuality, which, in turn, leads to a change in neural circuit connectivity and disruption of normal behavior. Our results expose a previously uncharacterized basis of circuit malfunction, and a possible underlying cause of neurological diseases.

Epithelium Expression and Function of Retinoid Receptors in Asthma

2008 ◽  
Vol 38 (3) ◽  
pp. 276-282 ◽  
Author(s):  
Anne Druilhe ◽  
Jean-Marie Zahm ◽  
Laurent Benayoun ◽  
Delphine El Mehdi ◽  
Martine Grandsaigne ◽  
...  
Keyword(s):  
Retinoid Receptors ◽  
And Function

scholarly journals Pathophysiological Role of K2P Channels in Human Diseases

2021 ◽  
Vol 55 (S3) ◽  
pp. 65-86
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Ion Homeostasis ◽  
Human Diseases ◽  
Cellular Functions ◽  
Aberrant Expression ◽  
K2p Channels ◽  
And Function

The family of two-pore domain potassium (K2P) channels is critically involved in central cellular functions such as ion homeostasis, cell development, and excitability. K2P channels are widely expressed in different human cell types and organs. It is therefore not surprising that aberrant expression and function of K2P channels are related to a spectrum of human diseases, including cancer, autoimmune, CNS, cardiovascular, and urinary tract disorders. Despite homologies in structure, expression, and stimulus, the functional diversity of K2P channels leads to heterogeneous influences on human diseases. The role of individual K2P channels in different disorders depends on expression patterns and modulation in cellular functions. However, an imbalance of potassium homeostasis and action potentials contributes to most disease pathologies. In this review, we provide an overview of current knowledge on the role of K2P channels in human diseases. We look at altered channel expression and function, the potential underlying molecular mechanisms, and prospective research directions in the field of K2P channels.

A phase I/II randomized study of panobinostat and bicalutamide in castration-resistant prostate cancer (CRPC) patients progressing on second-line hormone therapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 156-156 ◽  
Author(s):  
A. C. Ferrari ◽  
M. N. Stein ◽  
J. J. Alumkal ◽  
A. Gomez-Pinillos ◽  
D. D. Catamero ◽  
...  
Keyword(s):  
Randomized Study ◽  
Maximum Tolerated Dose ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Aberrant Expression ◽  
Castration Resistant ◽  
Deacetylase Inhibitor ◽  
Adequate Organ Function ◽  
Ecog Ps ◽  
And Function

156 Background: Aberrant expression and function of the androgen receptor (AR) is determinant of CRPC progression. We previously demonstrated that the histone-deacetylase inhibitor panobinostat (PAN) decreased AR levels and reversed resistance of androgen-independent AI-LNCaP and Rv1 cells to the antiandrogen bicalutamide (Bic). We designed a ph-I/II study to determine whether PAN would restore the sensitivity to Bic in CRPC patients (pts). We report the ph-I results evaluating safety and maximum tolerated dose (MTD) of Bic combined with oral, intermittent PAN. Methods: Men with CRPC and limited bone metastasis, ECOG PS 0-2, PSA>2 ng/ml (or <2 + new metastases), adequate organ function and QTc<450 ms progressing on at least two prior hormones including antiandrogens were assigned each to one of 3 cohorts (C) for treatment with Bic 50 mg PO daily with oral PAN at 3 dose levels: C1, 20 mg tri-wkly (60 mg/wk) 2 of 3 wks; C2: 30 mg tri-wkly (90mg/wk) 2 of 3 wks, 40 mg PO tri-wkly (120mg/wk) 3 of 3 wks. Cycles (Cy) repeated every 21 days. Minimum treatment was 3 wks. Treatment could continue if clinical benefit. DLT were: grade (G) 3-4 febrile neutropenia >5 days and/or hospitalization; G3 thrombocytopenia with bleeding; QTcF>500 ms any G4 except nausea, vomiting, or diarrhea. Results: Nine men, median (m) 65 yrs were treated in cohorts of three. mPSA at entry 9.26 ng/mL (IQR:8.24), mCy number, 6 (IQR: 5). MTD was not reached. All experienced some grade of toxicity attributable to PAN. Toxicity: no G4, only G3 was thrombocytopenia without bleeding in 3 pts (1 in C1, 2 in C3) that resolved spontaneously and controlled by dose reduction; G2: thrombocytopenia in 3, fatigue 2, high cholesterol 2, hypothyroidism 2; G1 thrombocytopenia in 2, fatigue 3, dyspepsia 3, anorexia 2. PSA decline ≥50% was achieved in 2 pts, stable PSA in 3 pts. Ph-II recommended PAN doses: Arm A: 40 mg tri-wkly (120 mg/wk) 2 of 3 wks; Arm B: 20 mg tri-wkly (60 mg/wk) 2 of 3wks with Bic 50 mg/daily. Conclusions: Oral, intermittent PAN in combination with daily Bic is well tolerated in CRPC pts progressing on second line hormones and shows promising PSA responses suggesting anti-AR activity. Ph-II is ongoing. [Table: see text]

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