4,4'­Bond secalonic acid D targets SP cells and inhibits metastasis in hepatocellular carcinoma.

The existence of cancer stem cells (CSCs) is considered to be the main reason for chemoresistance, metastasis and the ultimate failure of treatment in hepatocellular carcinoma (HCC). However, there are a few chemical agents that may inhibit CSCs. The present study identified that 4,4'­bond secalonic acid D (4,4'­SAD), a compound isolated from the marine­derived fungus Penicillium oxalicum, inhibited the growth of side population (SP) cells isolated from human liver cancer cell lines PLC/PRF/5 and HuH­7 by attenuating the expression of ATP­binding cassette superfamily G member 2. Furthermore, the results of wound healing, Transwell, western blotting and reverse transcription­quantitative PCR assays demonstrated that 4,4'­SAD suppressed the invasion and migration of SP cells by downregulating matrix metallopeptidase 9 (MMP­9) and upregulating the antagonist tissue inhibitor of metalloproteinases 1 in vitro. Moreover, in vivo study results found that 4,4'­SAD had anti­lung metastasis efficacy via the decrease of MMP­9 expression in the H22 HCC model of Kunming mice. Therefore, the present study identified the potential of 4,4'­SAD as a promising candidate for the treatment of advanced liver cancer.

Impact of treatment modality on long-term survival of stage IA small-cell lung cancer patients: a cohort study of the U.S. SEER database.

BACKGROUND: The optimal treatment modality for patients with stage IA (T1N0M0) small-cell lung cancer (SCLC) is still unclear. METHODS: Patients who received surgical resection or chemo-radiotherapy (CRT) between January 2004 and December 2014 were identified from The Surveillance, Epidemiology and End Results (SEER) database. Surgical resection included lobectomy, wedge resection, segmentectomy with lymphadenectomy [examined lymph node (ELN) ≥1]. Propensity score match analysis was utilized to balance the baseline characteristics. RESULTS: A total of 686 stage IA SCLC cases were included: 337 patients underwent surgery and 349 patients were treated by CRT alone. Surgery achieved a better outcome than CRT alone, with an adjusted hazard ratio (HR) of 0.495. Patients who underwent lobectomy demonstrated a longer overall survival (OS), compared to those who received sublobectomy (crude cohort, median OS, 69 vs. 38 months; match cohort, median OS, 67 vs. 38 months). Patients with ELN >7 presented with longer OS than those with ELN ≤7 (crude cohort, median OS, 91 vs. 49 months; matched cohort, median OS, 91 vs. 54 months). The additional efficacy of chemotherapy or radiotherapy in patients receiving lobectomy was observed. The best prognosis was achieved in the lobectomy plus CRT cohort, with a 5-year survival rate of 73.5%. CONCLUSIONS: The prolonged survival associated with lobectomy and chemotherapy or radiotherapy presents a viable treatment option in the management of patients with stage IA SCLC.

Prevalence And Clinical Significance Of Oncogenic CD79B And MYD88 Mutations In Primary Testicular Diffuse Large B-Cell Lymphoma: A Retrospective Study In China.

PURPOSE: In this study, we investigated the prevalence of CD79B and MYD88 mutations and their relation to clinical characteristics in a cohort of Chinese patients with primary testicular diffuse large B cell lymphoma (PT-DLBCL). PATIENTS AND METHODS: We examined the mutational status of CD79B and MYD88 by Sanger sequencing, and the gene amplification and protein expression of MYD88 in tissue samples from 30 cases of PT-DLBCL by quantitative polymerase chain reaction and immunohistochemistry, respectively. Western blotting was used to analyze phosphorylated STAT3 (p-STAT3) and phosphorylated p65 (p-p65) protein expression in cell lines harboring retroviral constructs for WT MYD88 or MYD88 mutant. RESULTS: Immunophenotypically, MYD88 protein staining was positive in 26/30 (86.67%) cases, and 23/30 (76.7%) cases tested positive for p65 in the nucleus. Genetically, CD79B mutation was found in 13/30 (43.3%) cases, whereas the MYD88 L265P mutation was found in 18/30 (60.0%) cases. Interestingly, CD79B and MYD88 mutations were more prevalent in the non-germinal center B cell (GCB) subtype (83.3% and 76.9%, respectively) and were relatively rare in the GCB subtype (16.7% and 23.1%, respectively). Furthermore, although MYD88 was significantly amplified in PT-DLBCL, the amplification status showed no correlation with its mutational status and protein expression. Clinicopathological comparison between the mutant and wild-type group showed that both CD79B mutation and MYD88 L265P were not significantly correlated with age, anatomical site, Ann Arbor stage, non-GCB/GCB subtype, p65 protein expression, BCL-2 protein expression, or BCL-2/c-MYC double expression (P>0.05). Survival analyses showed that high IPI and advanced stage (stage III-IV) associated with worse outcome (P<0.05). The expression of p-STAT3 and p-p65 protein was upregulated in the mutant group, indicating that MYD88 mutant activated NF-κB and JAK-STAT3 signaling. CONCLUSION: Our results suggest that MYD88 and CD79B mutations are important drivers of immune-privileged site-associated DLBCL and highlight potential therapeutic targets for personalized treatment.