Leukotriene receptor expression in esophageal squamous cell cancer and non-transformed esophageal epithelium: a matched case control study

Chang

et al. 2017

IJMS

Developing novel chemo-prevention techniques and advancing treatment are key elements to beating lung cancer, the most common cause of cancer mortality worldwide. Our previous cohort study showed that cysteinyl leukotriene receptor antagonists, mainly montelukast, decreased the lung cancer risk in asthma patients. In the current study, we conducted in vivo and in vitro experiments to demonstrate the inhibiting effect of montelukast on lung cancer and to investigate the underlying mechanisms. Using Lewis lung carcinoma-bearing mice, we showed that feeding montelukast significantly delayed the tumor growth in mice (p < 0.0001). Montelukast inhibited cell proliferation and colony formation and induced the cell death of lung cancer cells. Further investigation showed the down-regulation of B-cell lymphoma 2 (Bcl-2), up-regulation of Bcl-2 homologous antagonist/killer (Bak), and nuclear translocation of apoptosis-inducing factor (AIF) in montelukast-treated lung cancer cells. Montelukast also markedly decreased the phosphorylation of several proteins, such as with no lysine 1 (WNK1), protein kinase B (Akt), extracellular signal-regulated kinase 1/2 (Erk1/2), MAPK/Erk kinase (MEK), and proline-rich Akt substrate of 40-kDa (PRAS40), which might contribute to cell death. In conclusion, montelukast induced lung cancer cell death via the nuclear translocation of AIF. This study confirmed the chemo-preventive effect of montelukast shown in our previous cohort study. The utility of montelukast in cancer prevention and treatment thus deserves further studies.

Section: Discussionmentioning

confidence: 99%

Montelukast Induces Apoptosis-Inducing Factor-Mediated Cell Death of Lung Cancer Cells

Chang

et al. 2017

IJMS

BioMed Research International

“…Reduced GJA1 expression was associated with high levels of preoperative PSA, high Gleason score, and advanced pT stage and was an independent predictor for shortened postoperative BCR-free survival [ 37 ]. Forced expression of GJA1 induced apoptosis of PCa cells by downregulation of Bcl-2 expression and upregulation of caspase-3 activity [ 38 ]. By immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses, Venerito et al found CYSLTR1 expression was decreased by 0.26-fold in esophageal squamous cell cancer tissues compared to control mucosa [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Coexpression Network Analysis Identifies a Novel Nine-RNA Signature to Improve Prognostic Prediction for Prostate Cancer Patients

Cai

Chen

et al. 2020

Background. Prostate cancer (PCa) is the most common malignancy and the leading cause of cancer death in men. Recent studies suggest the molecular signature was more effective than the clinical indicators for the prognostic prediction, but all of the known studies focused on a single RNA type. The present study was to develop a new prognostic signature by integrating long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) and evaluate its prognostic performance. Methods. The RNA expression data of PCa patients were downloaded from The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus database (GSE17951, GSE7076, and GSE16560). The PCa-driven modules were identified by constructing a weighted gene coexpression network, the corresponding genes of which were overlapped with differentially expressed RNAs (DERs) screened by the MetaDE package. The optimal prognostic signature was screened using the least absolute shrinkage and selection operator analysis. The prognostic performance and functions of the combined prognostic signature was then assessed. Results. Twelve PCa-driven modules were identified using TCGA dataset and validated in the GSE17951 and GSE7076 datasets, and six of them were considered to be preserved. A total of 217 genes in these 6 modules were overlapped with 699 DERs, from which a nine-gene prognostic signature was identified (including 3 lncRNAs and 6 mRNAs), and the risk score of each patient was calculated. The overall survival was significantly shortened in patients having the risk score higher than the cut-off, which was demonstrated in TCGA (p=5.063E−03) dataset and validated in the GSE16560 (p=3.268E−02) dataset. The prediction accuracy of this risk score was higher than that of clinical indicators (the Gleason score and prostate-specific antigen) or the single RNA type, with the area under the receiver operator characteristic curve of 0.945. Besides, some new therapeutic targets and mechanisms (MAGI2-AS3-SPARC/GJA1/CYSLTR1, DLG5-AS1-DEFB1, and RHPN1-AS1-CDC45/ORC) were also revealed. Conclusion. The risk score system established in this study may provide a novel reliable method to identify PCa patients at a high risk of death.

Medicinal Research Reviews

“…A significant upregulation of testican‐1 (SPOCK1) in OSCC patients compared to healthy control (HC) implied that SPOCK1 could serve as an early biomarker as well as prognostic marker due to tobacco use . Significant intracellular proteins for the early detection of ESCC include the proteasome activator subunit 2 β (PA28β) protein, leukotriene B4 receptor (LTB4R) protein, cysteinyl leukotriene receptor 2 (CYSLTR2) protein, and glutathione S‐transferase omega 1 (GSTO1) protein . PA28β and CYSLTR2 are downregulated; whereas, LTB4R and GSTO1 are upregulated in the ESCC tissues.…”

Section: Biomarkers In Oscc and Esccmentioning

confidence: 99%

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Khan

Relitti

Brindisi

et al. 2019

Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC.Additionally, we provide a viewpoint on the state of the art Tuhina Khan and Nicola Relitti contributed equally to this work. and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC. K E Y W O R D S autophagy, autophagy modulators, biomarkers, esophageal squamous cell carcinoma, exosomes, oral squamous cell carcinoma, targeted therapy 1 | INTRODUCTION Oral squamous cell carcinoma (OSCC) is the predominant malignant neoplasm of the oral cavity followed by verrucous carcinoma, undifferentiated carcinoma, and small salivary adenocarcinoma. 1 Esophageal squamous cell carcinoma (ESCC) is the first histological type and accounts for 80% of cases of esophageal cancer. 2 OSCC and ESCC are indicated as one of the most common cancers by the International Union Against Cancer with an annual incidence of 275 000 and 456 000 cases worldwide, respectively. 3,4 The primary etiology in both OSCC and ESCC is attributed to the environmental factors (tobacco abuse, alcohol consumption), genetic factors (eg, mutations in enzymes), viral factors (human papilloma virus [HPV] infection), and/or the coexistence of these factors. Alcohol intake and tobacco use are responsible for at least 75% of these carcinomas. The underlying initiation and progression mechanisms of OSCC and ESCC are generally characterized by the accumulation of serial epigenetic and genetic alterations, which eventually lead to uncontrolled proliferation of the mutated cells, followed by vigorous cell division. 5,7 Early-stage OSCC detection displays an 80% survival rate at 5 years, while detection at advanced stage leads to survival rates ranging from 20% to 40%. 6 In ESCC, the 5-year survival rate for early-stage detection may reach 85%, whereas a dr...