Ovarian cancer is the leading cause of death in gynecological diseases. Thyroid hormone promotes proliferation of ovarian cancer cells via cell surface receptor integrin αvβ3 that activates extracellular regulated kinase (ERK1/2). However, the mechanisms are still not fully understood. Thyroxine (T4) at a physiologic total hormone concentration (10−7 M) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3′-triiodo-L-thyronine (T3) at a supraphysiologic concentration. Thyroid hormone (T4 and T3) treatment of human ovarian cancer cells resulted in enhanced activation of the Ras/MAPK(ERK1/2) signal transduction pathway. An MEK inhibitor (PD98059) blocked hormone-induced cell proliferation but not ER phosphorylation. Knock-down of either integrin αv or β3 by RNAi blocked thyroid hormone-induced phosphorylation of ERK1/2. We also found that thyroid hormone causes elevated phosphorylation and nuclear enrichment of estrogen receptor α (ERα). Confocal microscopy indicated that both T4 and estradiol (E2) caused nuclear translocation of integrin αv and phosphorylation of ERα. The specific ERα antagonist (ICI 182,780; fulvestrant) blocked T4-induced ERK1/2 activation, ERα phosphorylation, PCNA expression and proliferation. The nuclear co-localization of integrin αv and phosphorylated ERα was inhibited by ICI. ICI time-course studies indicated that mechanisms involved in T4- and E2-induced nuclear co-localization of phosphorylated ERα and integrin αv are dissimilar. Chromatin immunoprecipitation results showed that T4-induced binding of integrin αv monomer to ERα promoter and this was reduced by ICI. In summary, thyroid hormone stimulates proliferation of ovarian cancer cells via crosstalk between integrin αv and ERα, mimicking functions of E2.

Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated β-catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.

Objective A real-Taiwan experience to deal with near-term pregnant woman infected by severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus disease 2019, COVID-19) is extremely limited. We described the first case in Taiwan. Case report A 30-year-old woman, primigravida had a laboratory-confirmed COVID-19 infection at 36 gestational weeks (GW). She was asymptomatic. Ten days later, she was hospitalized and receive a selective cesarean section with a term baby weighted 3142 gm (Apgar score 8 and 9 at 1st and 5th minute, respectively) at 38 GW. No evidence of in utero and direct transmission was found and newborn was free of COVID-19. Conclusions It is still uncertain whether timing or mode of delivery is appropriate in SARS-CoV-2 infected pregnant woman in near term, but we suggested that a selective delivery time at 38 GW or later, regardless of which mode of delivery is finally decided, can be considered.