Functional promoter rs2868371 variant of HSPB1 associates with radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with radio(chemo)therapy
ABSTRACT We investigated the association between single-nucleotide polymorphisms (SNPs) in the heat shock protein beta-1 (HSPB1) gene and the risk of radiation-induced esophageal toxicity (RIET) in patients with non-small-cell lung cancer (NSCLC).
The experimental dataset comprised 120 NSCLC patients who were treated with radio(chemo)therapy between 2005 and 2009, when novel radiation techniques were implemented at MD Anderson. The validation dataset comprised 181 NSCLC patients treated between 1998 and 2004. We genotyped two SNPs of the HSPB1 gene (rs2868370 and rs2868371) by TaqMan assay.
Univariate and multivariate analyses of the experimental dataset showed that the CG/GG genotypes of HSPB1 rs2868371 were associated with significantly lower risk of grade ⩾3 RIET than the CC genotype (univariate hazard ratio [HR] 0.30; 95% confidence interval [CI], 0.10-0.91; P=0.033; multivariate HR 0.29; 95% CI, 0.09-0.97; P=0.045). This difference in risk was replicated in the validation cohort despite the different radiation techniques used during that period.
The CG/GG genotypes of HSPB1 rs2868371 were associated with lower risk of RIET, compared with the CC genotype in patients with NSCLC treated with radio(chemo)therapy. This finding should be validated in large multi-institutional prospective trials.
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ABSTRACT: Objective. This study aims to explore the correlations of genetic polymorphisms in LIG4 and HSPB1 genes with the radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), in lung cancer patients. Methods. A total of 160 lung cancer patients, who were diagnosed with inoperable lung cancer and received radiotherapy, were included in the present study from September 2009 to December 2011. TaqMan Real-Time PCR (RT-PCR) was used to verify the SNPs of LIG4 and HSPB1 genes. Chi-square criterion was used to compare the differences in demographic characteristics, exposure to risk factors, and SNPs genotypes. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by logistic regression analysis. All statistical analyses were conducted in SPSS 18.0. Results. A total of 32 (20.0%) lung cancer patients had RP after receiving radiotherapy. Of the 32 cases, 4 cases were of grade 2, 24 cases were of grade 3, and 4 cases were of grade 4. However, our results indicated that the general condition and treatment of all patients had no significant difference with RP risk (P > 0.05). Meanwhile, our results revealed that there was no significant association between the frequencies of LIG4 rs1805388 and HSPB1 rs2868371 genotype distribution and the risk of RP (P > 0.05). Conclusion. In conclusion, we demonstrated that the genetic polymorphisms in LIG4 rs1805388 and HSPB1 rs2868371 were not obviously correlated with the risk of RP and RILI of lung cancer.01/2015; 2015:860373. DOI:10.1155/2015/860373
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ABSTRACT: Multi-purpose plants are frequently protected with mechanical safety devices like safety valves or bursting disks. Due to many changes of recipes it must be checked regularly whether the safety devices are sufficiently sized. But the sizing procedure of individual safety devices can be very tedious. Therefore energy specific relief areas (effective relief area per kW of energy input) have been determined for approx. 60 typical solvents. They are indicated for reactors with safety devices which have a set pressure of 7 bar (abs) or 11 bar (abs). These values are independent of the size of the reactors for vaporizing systems and arbitrary safety valves. The energy specific relief areas allow the minimum required relief area quickly to recalculate if the energy input of the reactor is known. In addition, the application of solvents in multi-purpose plants can be evaluated from a safety point of few.The energy specific relief areas are calculated based on a relief of two-phase gas/liquid mixtures. The data have been determined with the non-equilibrium HNE-DS method, which takes into account the boiling delay of the liquid in the safety device and the slip between gases and liquids. The method is recommended in the international standard ISO 4126 part 10. In addition, practical advice and possible improvements are outlined. The method leads to significantly smaller relief areas than according to the API 520. For multi-purpose plants with available safety devices this method allows for a considerable expansion of the application range of reactors.Journal of Loss Prevention in the Process Industries 01/2012; 83(6). DOI:10.1016/j.jlp.2011.08.008 · 1.35 Impact Factor
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ABSTRACT: Patients with unresectable stage III non-small-cell lung cancer receiving concurrent chemoradiotherapy often develop esophagitis that may lead to unplanned treatment interruptions, which may severely reduce rates of locoregional tumor control and survival. No effectivetreatment that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of normal tissue protection using epigallocatechin-3-gallate (EGCG) has been reported, its actual clinical practicability remains obscure. This is a phase I study of EGCG in combination with standard chemoradiation in surgically unresectable stage III non-small-cell lung cancer. Chemotherapy (cisplatin and etoposide) was given concurrently with radiation. EGCG solution was swallowed three times a day after the occurrence of grade 2 esophagitis at six concentration levels and dose escalation followed a standard phase I design. Esophageal toxicity and patient-reported pain was recorded weekly. Twenty-four patients with AJCC stage IIIA (six) and IIIB (eighteen) completed the course of therapy. Twelve had squamous histology, ten adenocarcinoma, and two not specified. Patients were treated in six cohorts at six dose levels of EGCG. RT was not interrupted with a median dose of 64Gy. There were no dose-limiting toxicities reported in all EGCG dosing tiers. Dramatic regression of esophagitis to grade 0/1 was observed in 22 of 24 patients, whereas grade 2 esophagitis persisted in 2 of 24 patients at the end of radiotherapy. The pain score was also reduced from a mean of 4.58 (N=24), 1.29 (N=24), 1.42 (N=24), 0.96 (N=23) to 1.13 (N=16) every week in turn. We conclude that the oral administration of EGCG is feasible, safe and effective. The phase II recommended concentration is 440μmol/L.Radiotherapy and Oncology 01/2014; 110(1). DOI:10.1016/j.radonc.2013.10.014 · 4.86 Impact Factor