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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Minichromosome maintenance protein 2 correlates with the malignant status and regulates proliferation and cell cycle in lung squamous cell carcinoma

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          Abstract

          Background

          Minichromosome maintenance protein 2 (MCM2), which is a member of MCM family, has been found to be a relevant marker for progression and prognosis in a variety of human cancers. Due to lack of effective therapeutic target in lung squamous cell carcinoma (LUSC) patients, the aim of our study was to screen and identify biomarkers which are associated to clinicopathological characteristics including prognosis in LUSC patients.

          Methods

          The expression status of MCM2 in lung cancer was analyzed using the publicly available Gene Expression Omnibus databases (GSE3268 and GSE10245). The mRNA and protein expression of MCM2 in lung cancer tissues and cell lines was detected by quantitative real-time PCR and Western blot, and the association between MCM2 expression and clinicopathological factors was analyzed by immunohistochemistry. The loss-of-function study of MCM2 was conducted in LUSC cell lines.

          Results

          In our study, we found MCM2 expression was increased in LUSC tissues compared with paired adjacent normal lung tissues or lung adenocarcinoma tissues through analyzing microarray data sets (GSE3268 and GSE10245), which confirmed that MCM2 mRNA and protein were overexpressed in LUSC tissues and cell lines. Meanwhile, we analyzed the association between MCM2 protein expression and clinicopathological characteristics of LUSC patients, and found high expression of MCM2 protein was obviously associated with malign differentiated degree, advanced clinical stage, large tumor size, more lymph node metastasis and present distant metastasis. The survival analysis showed MCM2 overexpression was an independent unfavorable prognostic factor for LUSC patients.

          Conclusion

          MCM2 is involved in the development and progression of LUSC as an oncogene, and thereby may act as a potential therapeutic target for LUSC patients.

          Most cited references46

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          Current Landscape of Targeted Therapy in Lung Cancer.

          Lung cancer is the leading cause of cancer mortality worldwide. Comprehensive genomic profiling of lung cancers revealed their genetic heterogeneity and complexity and identified numerous targetable oncogenic driver alterations. These molecular profiling efforts have made it possible to exploit the potential of molecularly targeted therapies. Selection of patients for targeted therapies is becoming biomarker-driven, where the oncogenic drivers in patient tumors are first identified, and subsequently patients bearing drug-sensitizing genetic aberrations are matched to the appropriate targeted therapy. Success of this design of clinical trials and practice was first demonstrated in EGFR inhibitor trials in lung cancer and has since been incorporated into subsequent targeted therapy trials including ALK-, ROS1-, and BRAF V600E-targeted therapies. In this review we discuss the current landscape of clinically approved and other promising molecularly targeted approaches for the treatment of lung cancers, the challenges with these approaches, and the strategies that could be deployed to overcome these challenges.
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            Japanese lung cancer registry study of 11,663 surgical cases in 2004: demographic and prognosis changes over decade.

            The Japan Lung Cancer Society, the Japanese Association for Chest Surgery, and the Japanese Respiratory Society jointly established the Japanese Joint Committee for Lung Cancer Registration, which has regularly conducted lung cancer registries for surgical cases in 5-year periods. We analyzed data obtained in these registries to reveal the most recent surgical outcomes and trends related to lung cancer surgery in Japan. Using data from the registry in 2010 for cases of surgery performed in 2004, demographics, surgical results, and stage-specific prognoses were analyzed. In addition, trends for those parameters over 10 years were assessed. The 5-year survival rate for all cases (n = 11,663, 7369 males, mean age 66.7 years) was 69.6%. The 5-year survival rates by c-stage and p-stage were as follow: IA, 82.0% (n = 6295) and 86.8% (n = 4978); IB, 66.8% (n = 2339) and 73.9% (n = 2552); IIA, 54.5% (n = 819) and 61.6% (n = 941); IIB, 46.4% (n = 648) and 49.8% (n = 848); IIIA, 42.8% (n = 1216) and 40.9% (n = 1804); IIIB, 40.3% (n = 90) and 27.8% (n = 106); and IV, 31.4% (n = 256) and 27.9% (n = 434), respectively. The percentages of female patients, cases with adenocarcinoma, stage I or II disease, and tumors sized less than 2 cm were increased, while those of operative and hospital deaths were decreased. Furthermore, the prognoses of all cases and cases in each stage improved over the decade. In Japanese cases of lung cancer surgery, demographics, surgical results, and stage-specific prognoses changed over the 10-year study period, while the 5-year survival rate for surgical cases improved to 69.6% in 2004.
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              The prognostic molecular markers in hepatocellular carcinoma.

              The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor microvessel density (MVD) have been evaluated and found to be of prognostic significance. Body fluid (particularly blood and urinary) testing for biomarkers is easily accessible and useful in clinical patients. The prognostic significance of circulating DNA in plasma or serum, and its genetic alterations in HCC are other important trends. More attention should be paid to these two areas in future. As the progress of the human genome project advances, so does a clearer understanding of tumor biology, and more and more new prognostic markers with high sensitivity and specificity will be found and used in clinical assays. However, the combination of some items, i.e., the pathological features and some biomarkers mentioned above, seems to be more practical for now.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                20 August 2018
                : 11
                : 5025-5034
                Affiliations
                [1 ]Department of Respiratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, People’s Republic of China, shanchangting_jn@ 123456163.com
                [2 ]Department of Emergency, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, People’s Republic of China
                [3 ]Department of Paediatric Surgery, Jining No 1 People’s Hospital, Jining, Shandong 272011, People’s Republic of China
                Author notes
                Correspondence: Changting Shan, Department of Respiratory Medicine, Affiliated Hospital of Jining Medical University, No 89 Guhuai Road, Jining 272029, Shandong, People’s Republic of China, Email shanchangting_jn@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                ott-11-5025
                10.2147/OTT.S169002
                6109654
                30174440
                f8e797d6-4b20-4055-872d-851f83e997bf
                © 2018 Wu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Oncology & Radiotherapy
                mcm2,lung cancer,lung squamous cell carcinoma,biomarker,proliferation,cell cycle

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