Objective To evaluate the prognostic impact of MRI-detected prevertebral space involvement in nasopharyngeal carcinoma (NPC) treated with radiotherapy and chemotherapy.Methods A retrospective analysis was performed on the clinical data of 333 patients who had newly diagnosed biopsyproven NPC without distant metastasis from 2005 to 2007.All patients underwent MRI scans of the nasopharynx and neck and were treated with two-and three-dimensional radiotherapy without or without chemotherapy.The Kaplan-Meier method was used to calculate overall survival (OS),distant metastasis-free survival (DMFS),and locoregional relapse-free survival (LRFS),and the log-rank test was used for survival difference analysis;the Cox proportional hazards regression analysis was used to assess the prognostic value of prevertebral space involvement.Results The follow-up rate was 95.2％.Prevertebral space involvement was seen in 139(41.7％) of these patients.The patients with prevertebral space involvement had significantly higher T stage and clinical stage than those without prevertebral space involvement (x2 =90.41,P =0.000;x2 =54.03,P =0.000).The 5-year OS,DMFS,and LRFS for NPC patients with and without prevertebral space involvement were 58.8％ vs.77.5％ (x2 =11.95,P =0.000),77.8％ vs.85.0％(x2=2.56,P=0.110),and 88.3％ vs.91.8％ (x2=1.51,P=0.220),respectively.After adjusting for N stage,a significant difference was still seen between the two groups with regard to 5-year OS (x2 =9.93,P =0.002).The multivariate analysis showed that prevertebral space involvement was not the independent prognostic factor for OS,DMFS,and LRFS (x2 =0.43,P =0.512 ; x2 =0.08,P =0.783 ; x2 =0.00,P =0.971).Conclusions The frequency of prevertebral space involvement is very high in NPC.The OS for the patients with prevertebral space involvement is significantly lower than those without prevertebral space involvement.But prevertebral space involvement is not the independent prognostic factor in NPC patients.

Objective To investigate the prognostic value of maximum diameter in axial plane of primary tumor (MDAPPT) on MRI in nasopharyngeal carcinoma (NPC).Methods From 2005 to 2007,333 patients with newly diagnosed and biopsy-proven NPC without distant metastasis,who underwent MRI scans of the nasopharynx and neck,were included in our study.MDAPPT was measured on MRI.The univariate analysis with the log-rank test and multivariate analysis with the Cox proportional hazards model were used to analyze the relationship between MDAPPT and prognosis.Results The median values of MDAPPT in patients with T1,T2,T3,and T4 NPC were 21.2,30.0,38.0,and 52.3 mm,respectively.For all patients with a MDAPPT of ≤30 mm,＞ 30-50 mm,and ＞ 50 mm,the 5-year overall survival (OS) rates were 81.3％,70.1％,and 51.5％,respectively (P =0.000) ; the 5-year progression-free survival (PFS) rates were 81.3％,70.0％,and 48.9％,respectively (P =0.000) ;the 5-year distant metastasisfree survival (DMFS) rates were 85.5 ％,86.5 ％,and 67.2 ％,respectively (P =0.000) ; the 5-year local relapse-free survival (LRFS) rates were 97.7％,91.5％,and 83.3％,respectively (P =0.013).The multivariate analysis showed that MDAPPT was a prognostic factor for PFS and DMFS.For the T3-T4 patients with a MDAPPT of ≤50 mm and ＞50 mm,the 5-year OS rates were 69.4％ and 52.2％ (P =0.004),the 5-year PFS rates were 68.0％ and 49.6％ (P =0.001),and the 5-year DMFS rates were 84.0％ and 66.8％ (P=0.001).In the patients with a MDAPPT ≤30 mm,the 5-year LRFS rates for those with T1,T2,T3,and T4 NPC were 10 0 ％,9 5.8 ％,9 6.3 ％,and 10 0 ％,respectively (P =0.6 4 3).Conclusions MDAPPT is a prognostic factor for PFS and DMFS in NPC,and it is an important prognostic factor in patients with T3-T4 NPC.In the NPC patients with a small MDAPPT,local control rate varies little in different T stages.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.