Clinical outcomes and prognostic factors of patients with epithelial ovarian cancer subjected to first-line treatment： a retrospective study of 251 cases

A total of 251 patients with epithelial ovarian cancer （EOC） treated between 2002 and 2008 was retrospectively analyzed to investigate the long-term outcomes and prognostic factors of these patients, particularly those who underwent primary debulking surgery followed by platinum-based chemotherapy. Clinico- pathological parameters, including progression-free survival （PFS） and overall survival （OS）, were also analyzed. The median follow-up period from the end of initial treatment to June 2010 was 58 months. The three-year PFS rate was 61.7% for International Federation of Gynecology and Obstetrics （FIGO） I-II, 19.9% for FIGO III-IV, and 33.9% for all stages. By comparison, the five-year PFS rate was 44.6% for FIGO I-II, 17.7% for FIGO III-IV, and 28.3% for all stages. The three-year OS rate was 67.9% for FIGO I-II, 41.7% for FIGO III IV, and 50.2% for all stages. The five-year OS rate was 52.7% for FIGO I-II, 30.8% for FIGO III-IV, and 39.2% for all stages. Univariate analysis revealed that advanced FIGO stage, serum CA125, and suboptimal debulking were significant factors affecting PFS and OS. In multivariate analysis, PFS was significantly influenced by FIGO stage and suboptimal debulking. However, OS was significantly influenced by advanced FIGO stage only. Our study confirms the efficacy of surgery followed by platinum-based chemotherapy for EOC. FIGO stage is considered as one of the most reliable predictors of the prognosis of patients with EOC.

Doxorubicin-conjugated pH-responsive gold nanorods for combined photothermal therapy and chemotherapy of cancer

Cancer chemotherapy can be hindered by drug resistance which leads to lower drug efficiency.Here,we have developed a drug delivery system that tethers doxorubicin to the surface of gold nanorods via a pHsensitive linkage(AuNRs@DOX),for a combined photothermal and chemical therapy for cancer.First,AuNRs@DOX is ingested by HepG2 liver cancer cells.After endocytosis,the acidic pH triggers the release of doxorubicin,which leads to chemotherapeutic effects.The gold nanorods are not only carriers of DOX,but also photothermal conversion agents.In the presence of an 808 nm near-infrared laser,AuNRs@DOX significantly enhance the cytotoxicity of doxorubicin via the photothermal effect,which induces elevated apoptosis of hepG2 cancer cells,leading to better therapeutic effects in vitro and in vivo.

The RNF20/40 complex regulates p53-dependent gene transcription and mRNA splicing

p53 is a key transcription factor to regulate gene transcription.However,the molecular mechanism of chromatin-associated p53 on gene transcription remains elusive.Here,using unbiased protein affinity purification,we found that the RNF20/40 complex associated with p53 on the chromatin.Further analyses indicated that p53 mediated the recruitment of the RNF20/40 complex to p53 target gene loci including p21 and PUMA loci and regulated the transcription of p21 and PUMA via the RNF20/40 complex-dependent histone H2B ubiquitination(ubH2B).Lacking the RNF20/40 complex suppressed not only ubH2B but also the generation of the mature mRNA of p21 and PUMA.Moreover,ubH2B was recognized by the ubiquitin-binding motif of pre-mRNA processing splicing factor 8(PRPF8),a subunit in the spliceosome,and PRPF8 was required for the maturation of the mRNA of p21 and PUMA.Our study unveils a novel p53-dependent pathway that regulates mRNA splicing for tumor suppression.