br It was reported that the
It was reported that the average human intakes of BBP, DBP and DEHP in German and US populations were 0.26–0.88 μg/kg/day, 0.84–5.22 μg/kg/day and 0.71–4.6 μg/kg/day, respectively (Koch and Calafat, 2009). Hartmann et al. reported that the median concentration of BBP metabolite in urine among Austrian population aged 6–15 and 18–81 years was 25 μg/ L (0.8 × 10−7 mol/L) (Hartmann et al., 2015). In present study, BBP concentrations used for the investigation of the proliferation-promotion effect as well as the underlying mechanism in prostate cancer Ferrostatin-1 were 10−6 and 10−7 mol/L, which was in line with the concentration in Hartmanns study. Moreover, in vitro cell culture experiment is usually conducted with relative high doses within short period of time, whereas humans may expose to toxicants at low doses with longer time or even whole life. Nevertheless, from the risk
assessment point of view, the study from this paper investigates the ‘hazard identification’ step, further studies on ‘human exposure’, ‘dose-response relationship’ would allow investigators to perform a proper ‘risk characterization’ of BBP. In summary, the present study revealed for the first time that BBP promoted the proliferation of prostate cancer cells through miR-34a/c-myc axis. These data could provide new insight into the involvement and the underlying molecular mechanism of phthalate esters in prostate cancer.
Conflicts of interests
The authors declare they have no actual or potential competing fi-nancial interests.
This work was supported by grants from the National Natural Science Foundation of China (No. 81072330, No. 81373005, No. 81202194), and by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Corcoran, C., Rani, S., O'Driscoll, L., 2014. miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression. Prostate 74 (13), 1320–1334.
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c-MET as a biomarker in patients with surgically resected non-small cell lung T cancer
Georgios Tsakonasa, , Johan Botlingb, Patrick Mickeb, Chris Rivardc, Linnea LaFleurb, Johanna Mattssonb, Teresa Boylec, Fred R. Hirschc, Simon Ekmana
a Thoracic Oncology Center, Theme Cancer, Karolinska University Hospital/Department of Oncology- Pathology, Karolinska Institutet, Stockholm, Sweden
b Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
c Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Background: c-MET protein overexpression has been proposed as a biomarker in non-small cell lung cancer (NSCLC), albeit its role in the clinical setting has not been firmly established yet.
Patients and methods: We designed a retrospective cohort study, consisting of 725 patients with surgically removed NSCLC. Immunohistochemistry (IHC) was conducted in tissue microarrays (TMA) from lung tumors and healthy tissue. IHC staining was quantified using H-scores (range 0–300). Association between c-MET H-score and overall survival (OS) as well as progression-free survival (PFS) was explored. Results: c-MET H-score ≥20 had a significant positive impact on OS in the multivariate analysis in the whole study population, HR = 0.79 (95%CI: 0.64−0.97). The prognostic eﬀect of c-MET H-score ≥20 was even
Conclusion: c-MET H-score ≥20 is a positive prognostic biomarker for OS in early stage NSCLC. This benefit seems to be strongly correlated to adjuvant chemotherapy, therefore rendering c-MET H-score ≥20 a possible predictive biomarker for platinum-based adjuvant chemotherapy in early stage NSCLC.
Hepatocyte Growth Factor (HGF) and its receptor cellular Mesenchymal Epithelial Transition factor (c-MET), a heterodimeric tyrosine kinase receptor, are frequently expressed in non-small cell lung cancer (NSCLC) and represents an oncogenic signaling pathway of major interest in NSCLC. c-MET protein overexpression, gene amplifi-cation and exon 14 splicing mutation (METex14) have been proposed as potential prognostic biomarkers as well as predictive biomarkers for targeted therapy, albeit their role in the clinical setting has not been firmly established yet [1,2].
c-MET protein is overexpressed in 13–36 % of primary lung cancer specimens and is often associated with poor prognosis [3–5]. Albeit, in the ETOP study by Bubendorf et al, neither c-MET overexpression nor MET gene amplification influenced prognosis in a large cohort of early stage NSCLC patients . In the brain metastatic setting, c-MET over-expression has been reported to be as high as 44.4% . The im-munohistochemistry (IHC) methods used to define c-MET