Prognostic role of TPL2 in early‑stage non‑small cell lung cancer

Non‑small cell lung cancer (NSCLC) accounts for ~70% of all lung cancer‑associated mortalities worldwide. The serine/threonine protein kinase tumor progression locus 2 [TPL2/MAP3 kinase 8 (MAP3K8)] may impact oncogenic events; however the role of TPL2 in lung carcinogenesis remains unclear. The present study was focused on the potential prognostic role of TPL2 in 101 patients with early‑stage NSCLC. Since TPL2 is a potential target of miR‑21, the association between TPL2 and miR‑21 expression was also examined. TPL2 and miR‑21 mRNA expression was quantified using reverse transcription quantitative polymerase chain reaction (RT‑qPCR). TPL2 protein levels were evaluated by immunohistochemistry (IHC). The present study identified that the mRNA expression of TPL2 was low in 52/101 (51%) cases and high in 49/101 (49%) cases. IHC analysis of TPL2 protein expression often demonstrated identical mRNA results. No statistically significant associations were observed between the mRNA expression of TPL2 and the predominant clinicopathological characteristics of the patients with NSCLC, as well as identifying no association between TPL2 and miR‑21. TPL2 mRNA expression was significantly higher in patients with NSCLC with good prognosis (disease‑free interval P=0.009; overall survival P=0.024), when compared with those of poor prognosis. Focusing on the difference in mRNA expression of TPL2 among the adenocarcinomas in affected patients, TPL2 was more highly expressed in lepidic adenocarcinomas compared with in the other subtypes (P=0.012). The present study is the first examination, to the best of our knowledge, of TPL2 in early‑stage NSCLC in relation to miR‑21, and in different adenocarcinoma subtypes. Future studies must clarify the mechanism by which TPL2 is involved in lung carcinogenesis due to its important translational implications

Let-7g and miR-21 expression in non-small cell lung cancer: correlation with clinicopathological and molecular features

MicroRNAs (miRNAs) play a key role in cancer pathogenesis and are involved in several human cancers, including non-small cell lung cancer (NSCLC). This study evaluated Let-7g and miR-21 expression by quantitative real-time PCR in 80 NSCLC patients and correlated the results with their main clinicopathological and molecular features. MiR-21 expression was significantly higher in NSCLC tissues compared to non-cancer lung tissues (p<0.0001), while no significant changes in Let-7g expression were observed between the tumor and normal lung tissues. Target prediction analysis led to the identification of 26 miR-21 and 24 Let-7g putative target genes that play important roles in cancer pathogenesis and progression. No significant association was observed between the analysed miRNAs and the main clinicopathological or molecular characteristics of the NSCLC patients, although both miRNAs were downregulated in squamous cell carcinomas compared to adenocarcinomas. Noteworthy, we observed a significant association between low Let-7g expression and metastatic lymph nodes at diagnosis (p=0.046), as well as between high miR-21 expression and K-Ras mutations (p=0.0003). Survival analysis did not show any significant correlation between prognosis and the analysed miRNAs, although the patients with a high Let-7g and miR-21 expression showed a significantly lower short-term progression-free survival (p=0.01 and p=0.0003, respectively) and overall survival (p=0.023 and p=0.0045, respectively). In conclusion, we showed that Let-7g and miR-21 expression was deregulated in NSCLC and we demonstrated a strong relationship between miR-21 overexpression and K-Ras mutations. Our data indicate that Let-7g and miR-21 profiling combined with the determination of K-Ras mutational status may be considered a useful biomarker for a more effective molecular characterization and clinical management of NSCLC patients

Inflamed shoulder structures in polymyalgia rheumatica with normal erythrocyte sedimentation rate

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Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study

Abstract Aims The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical outcome, was designed to explore the predictive value of multiple high-risk plaque features in the same coronary lesion [minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages] as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint. Methods and results From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicaltrial.gov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA 180° (HR 2.4, 95% CI 1.2–4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2–6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1–18.6). Conclusion The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events

Bioboosters in the treatment of rheumatic diseases: a comprehensive review of currently available biologics in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis

Fabrizio Cantini, Carlotta Nannini, Laura NiccoliSecond Division of Medicine, Rheumatology Unit, Hospital of Prato, ItalyAbstract: Immunologic research has clarified many aspects of the pathogenesis of inflammatory rheumatic disorders. Biologic drugs acting on different steps of the immune response, including cytokines, B- and T-cell lymphocytes, have been marketed over the past 10 years for the treatment of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). Randomized controlled trials (RCTs) of anti-cytokine agents in RA (including the anti-tumor necrosis factor alpha (TNFα) drugs infliximab, etanercept, adalimumab, golimumab, certolizumab, anti-interleukin (IL)-1 anakinra, and anti-IL-6 tocilizumab) demonstrated a significant efficacy compared to traditional therapies, if combined with methotrexate (MTX), as measured by ACR 20, 50 and 70 response criteria. The new therapies have also been demonstrated to be superior to MTX in slowing or halting articular damage. RCTs have shown the efficacy of anti-TNFα in AS patients through significant improvement of symptoms and function. Trials of anti-TNFα in PsA patients showed marked improvement of articular symptoms for psoriasis and radiological disease progression. More recent studies have demonstrated the efficacy of B-cell depletion with rituximab, and T-cell inactivation with abatacept. All these drugs have a satisfactory safety profile. This paper reviews the different aspects of efficacy and tolerability of biologics in the therapy of RA, AS, and PsA.Keywords: anti-TNF, anti-cytokine agents, rituximab, abatacept, rheumatoid arthritis, psoriatic arthritis, ankylosing spondyliti

Diagnosis and treatment of giant cell arteritis

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of unknown aetiology occurring in the elderly. It affects the cranial branches of the arteries originating from the aortic arch and is usually associated with markedly elevated acute-phase reactants. In 10-15% of cases the extra-cranial branches of the aortic arch are involved. GCA is closely related to polymyalgia rheumatica (PMR), although the relationship between the two disorders is still unclear. New-onset headache, scalp tenderness, jaw claudication, temporal artery abnormalities on physical examination, visual symptoms and associated PMR represent the most typical and frequent features of the disease. Systemic manifestations, including fever, anorexia and weight loss, are observed in 50% of cases. Less frequent manifestations are related to the central or peripheral nervous systems, the respiratory tract and extra-cranial large-vessel involvement. As GCA is characterized by a wide spectrum of clinical manifestations, it is important to recognize the different onset patterns of the disease and related diagnostic steps. The diagnosis is relatively straightforward in the presence of typical cranial manifestations, but it may be challenging in the case of a normal erythrocyte sedimentation rate, occult GCA or in patients with isolated extra-cranial features. Temporal artery biopsy still represents the gold standard for diagnosis, while the role of ultrasonography, high-resolution magnetic resonance imaging and positron emission tomography should be better addressed. Corticosteroids remain the therapy of choice. Data supporting the usefulness of antiplatelet agents and anticoagulants combined with corticosteroids to prevent ischaemic complications as well as the corticosteroid-sparing effect of methotrexate and anti-tumour necrosis factor-alpha drugs are limited and non-conclusive