PurposeCollagen 1A1 (COL1A1), RNA-binding and pre-mRNA Processing Factor (PRPF40A), and Uncoupling Protein 2 (UCP2) were identified as downstream effectors of cytoglobin (CYGB), which was shown implicated in tumour biology. Although these three genes have been previously associated with cancer, little is known about their status in lung malignancies.MethodsHereby, we investigated the expression and promoter methylation of COL1A1, PRPF40A, and UCP2 in 156 non-small cell lung cancer (NSCLC) and adjacent normal tissues.ResultsWe demonstrate that COL1A1 and PRPF40A mRNAs are significantly overexpressed in NSCLC (p < 1 × 10−4), while UCP2 exhibits a trend of upregulation (p = 0.066). Only COL1A1 promoter revealed hypermethylation in NSCLCs (36%), which was particularly evident in squamous cell carcinomas (p = 0.024) and in the tumours with moderate-to-good differentiation (p = 0.01). Transcript level of COL1A1, as well as PRPF40A and UCP2, exhibited striking association (p ≤ 0.001) with the expression of hypoxia markers. In addition, we demonstrate in lung cancer cell lines exposed to hypoxia or oxidative stress that COL1A1 transcription significantly responds to oxygen depletion, while other genes showed the modest upregulation in stress conditions.ConclusionIn conclusion, our data revealed that COL1A1, UCP2, and PRPF40A are novel players implicated in the complex network of hypoxia response in NSCLC.
Cytoglobin (CYGB) is frequently downregulated in many types of human malignancies, and its exogenous overexpression reduces proliferation of cancer cells. Despite its implied tumour suppressor (TSG) functions, its exact role in carcinogenesis remains unclear as CYGB upregulation is also associated with tumour hypoxia and aggressiveness. In this study, we explore the TSG role of CYGB, its influence on the phenotype of cancerous cells under stress conditions and the clinical significance of CYGB expression and promoter methylation in non-small cell lung cancer (NSCLC). DNA methylation-dependent expression silencing of CYGB is demonstrated in both clinical samples and cell lines. CYGB promoter was more frequently methylated in lung adenocarcinomas (P = 1.4 × 10(-4)). Demethylation by 5'-azadeoxycytidine partially restored CYGB expression in cell lines. Interestingly, trichostatin A triggered upregulation of CYGB expression in cancer cell lines and downregulation in non-tumourigenic ones. CYGB mRNA expression in NSCLC surgical specimens correlated with that of HIF1α and VEGFa (P < 1 × 10(-4)). Overexpression of CYGB in cancer cell lines reduced cell migration, invasion and anchorage-independent growth. Moreover, CYGB impaired cell proliferation, but only in the lung adenocarcinoma cell line (H358). Upon hydrogen peroxide treatment, CYGB protected cell viability, migratory potential and anchorage independence by attenuating oxidative injury. In hypoxia, CYGB overexpression decreased cell viability, augmented migration and anchorage independence in a cell-type-specific manner. In conclusion, CYGB revealed TSG properties in normoxia but promoted tumourigenic potential of the cells exposed to stress, suggesting a bimodal function in lung tumourigenesis, depending on cell type and microenvironmental conditions.
Background:
Peripheral artery disease is a common manifestation of systemic atherosclerosis which
strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery
disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and
research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over
the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious.
Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been
introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale
of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators
to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or
unstable.
Methods:
The aim of this study is to review the current evidence with respect to recently published studies concerning
the use of Novel anticoagulants in peripheral artery disease.
Results:
The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce
promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still
safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety
and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad
study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional
therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence
concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines
propose the use of novel oral anticoagulants.
Conclusion:
For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative
treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.
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