Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival(PFS) and overall survival(OS) between extensive-stage small-cell lung cancer(ES-SCLC) patients who acquired partial response(PR) or complete remission(CR) after two cycles of first-line chemotherapy with the etoposide plus cisplatin(EP) regimen and those who acquired PR or CR after four or six cycles.Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region(China) between November 2004 and May 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows.Results After a median follow-up of 293 days(range, 62–1531 days), all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months(95% CI, 5.1–6.9), and the median OS was 10.5 months(95% CI, 8.6–12.4). Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months(95% CI, 4.4–5.2), and the median OS was 7.5 months(95% CI, 6.8–8.2). Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.

曲妥珠单抗在Her-2过表达型转移性乳腺癌中应用的疗效与安全性(英文)

Objective: The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer(MBC) patients. The primary endpoint was overall response rate(ORR) and the second endpoint was clinical benefit rate(CBR) and toxcities. Methods: Estrogen receptor(ER)(–), progesterone receptor(PR)(–), Her-2(+++) patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group(H group) and 75 of them were assigned to the Control group(C group). They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results: Response rate(RR) of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant(P < 0.05). CBR of the two groups were 76.4%(H group) and 64.0%(C group), had significant difference(P < 0.05). Complete response rate(CRR) of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups(P = 0.055). Grade 3–4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy(17.6%) and 4 patients with chemotherapy(5.4%), with no statistical significance(P = 0.054). In the subgroup of antharcycline-containing regimens, Grade 1–4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracycline contained chemotherapy(H + ACCT arm; 40.9%, 9/22)], and 4 patients in the antharcyclinecontaining chemotherapy arm(ACCT arm; 12.5%, 4/32). There was statistical significant difference between the two arms(P < 0.05). Grade 3–4 cardiac toxicity, the occurance rates were 18.1%(4/22) in H + ACCT arm and 6.3%(2/32) in ACCT arm, and there was no significant statistical difference(P = 0.352). Grade 3–4 granulocytopenia in the H group and C group were 27.5%(14/51) and 26.7%(20/75), with no significant difference(P = 0.922). Conclusion: The efficiency of trastuzumab combining with chemotherapy using as first line regimen in Her-2 overexpressing MBC patients were exact. However, the long-term cardiac toxicity can be hidden troubles of trastuzumab using.

Acetylproteomics analyses reveal critical features of lysine-ε-acetylation in Arabidopsis and a role of 14-3-3 protein acetylation in alkaline response

Lysine-ε-acetylation(Kac)is a post-translational modification(PTM)that is critical for metabolic regulation and cell signaling in mammals.However,its prevalence and importance in plants remain to be determined.Employing high-resolution tandem mass spectrometry,we analyzed protein lysine acetylation in five representative Arabidopsis organs with 2~3 biological replicates per organ.A total of 2887 Kac proteins and 5929 Kac sites were identified.This comprehensive catalog allows us to analyze proteome-wide features of lysine acetylation.We found that Kac proteins tend to be more uniformly expressed in different organs,and the acetylation status exhibits little correlation with the gene expression level,indicating that acetylation is unlikely caused by stochastic processes.Kac preferentially targets evolutionarily conserved proteins and lysine residues,but only a small percentage of Kac proteins are orthologous between rat and Arabidopsis.A large portion of Kac proteins overlap with proteins modified by other PTMs including ubiquitination,SUMOylation and phosphorylation.Although acetylation,ubiquitination and SUMOylation all modify lysine residues,our analyses show that they rarely target the same sites.In addition,we found that“reader”proteins for acetylation and phosphorylation,i.e.,bromodomain-containing proteins and GRF(General Regulatory Factor)/14-3-3 proteins,are intensively modified by the two PTMs,suggesting that they are main crosstalk nodes between acetylation and phosphorylation signaling.Analyses of GRF6/14-3-3λreveal that the Kac level of GRF6 is decreased under alkaline stress,suggesting that acetylation represses plant alkaline response.Indeed,K56ac of GRF6 inhibits its binding to and subsequent activation of the plasma membrane H+-ATPase AHA2,leading to hypersensitivity to alkaline stress.These results provide valuable resources for protein acetylation studies in plants and reveal that protein acetylation suppresses phosphorylation output by acetylating GRF/14-3-3 proteins.

The chromatin remodeler BRAHMA recruits HISTONE DEACETYLASE6 to regulate root growth inhibition in response to phosphate starvation in Arabidopsis

Plasticity in root system architecture(RSA)allows plants to adapt to changing nutritional status in the soil.Phosphorus availability is a major determinant of crop yield,and RSA remodeling is critical to increasing the efficiency of phosphorus acquisition.Although substantial progress has been made in understanding the signaling mechanism driving phosphate starvation responses in plants,whether and how epigenetic regulatory mechanisms contribute is poorly understood.Here,we report that the Switch defective/sucrose non-fermentable(SWI/SNF)ATPase BRAHMA(BRM)is involved in the local response to phosphate(Pi)starvation.The loss of BRM function induces iron(Fe)accumulation through increased LOW PHOSPHATE ROOT1(LPR1)and LPR2 expression,reducing primary root length under Pi deficiency.We also demonstrate that BRM recruits the histone deacetylase(HDA)complex HDA6-HDC1 to facilitate histone H3 deacetylation at LPR loci,thereby negatively regulating local Pi deficiency responses.BRM is degraded under Pi deficiency conditions through the 26 S proteasome pathway,leading to increased histone H3 acetylation at the LPR loci.Collectively,our data suggest that the chromatin remodeler BRM,in concert with HDA6,negatively regulates Fe-dependent local Pi starvation responses by transcriptionally repressing the RSA-related genes LPR1 and LPR2 in Arabidopsis thaliana.