Transoral Videolaryngoscopic Surgery (TOVS)

Transoral videolaryngoscopic surgery (TOVS) for laryngopharyngeal cancer developed by Shiotani et al., uses the laparoscopic surgical system and distending laryngoscope. This method enables precise procedures and en bloc resection under a good view with videoendoscope in the structurally complex laryngopharynx. The major indications are Tis-2, and selected T3 lesions of hypopharyngeal, oropharyngeal, and supraglottic laryngeal cancer. TOVS is also considered for resectable rT1 and rT2 radiation failure cases and selected T3–4 advanced cases following neoadjuvant chemotherapy. Patients with resectable lymph node metastases are treated by neck dissection. Major contraindications are cricoarytenoid joint fixation, circumferential invasion of more than half, bilateral arytenoid invasion, and invasion to the thyroid cartilage, cricoid cartilage, hyoid bone, deep pharyngeal constrictor muscle. Oncological outcomes are good in long-term survival and larynx preservation rates with sparing radiation in half of the patients. However, advanced T stage and N3 cases showed a worse prognosis. Regarding functional outcome, swallowing function can maintain in most patients. Postoperative voice impairment can occur after wound healing. TOVS has some advantages particularly for hypopharyngeal cancer, in maneuver with smaller diameter instruments and tactile sense, and in less invasiveness without a tracheostomy, compared to other transoral surgeries

APPLICATION OF BLENDED CEMENT IN SHOTCRETE TO

The application of blended cements in shotcrete is investigated to reduce the environmental burden. Reduction of the environmental burden and meeting the required properties of quick setting and strength development are achieved using blended cements with blast furnace slag and a powder accelerator with a main component of calcium sulfo-aluminate. The powder accelerator is hydro-reactive and promotes quick setting and strength development in shotcrete. The reduced environmental burden of shotcrete with blended cement and powder accelerator are calculated

Generation of a transgene-free iPSC line and genetically modified line from a facioscapulohumeral muscular dystrophy type 2 (FSHD2) patient with SMCHD1 p.Lys607Ter mutation

Facioscapulohumeral muscular dystrophy type2 (FSHD2), which constitutes approximately 5% of total FSHD cases and develops the same symptoms as FSHD type 1 (FSHD1), is caused by various mutations in genes including SMCHD1. We report the generation and characterization of an iPSC line derived from an FSHD2 patient carrying the SMCHD1 p.Lys607Ter mutation and its gene-corrected iPSC line which are free from transgene. These iPSC lines maintained normal karyotype, presented typical morphology, expressed endogenous pluripotency markers, and could be differentiated into ectodermal, mesodermal and endodermal cells, confirming their pluripotency

YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers

Molecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome

Epstein-Barr virus-associated leukemic lymphoma after allogeneic stem cell transplantation

Leukemic Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative diseases (PTLD) following allogeneic hematopoietic stem cell transplantation are extremely rare. We can successfully treat an EBV-associated leukemic lymphoma patient with rituximab, cidofovir, and donor lymphocyte infusion (DLI). In the present case, EBV-specific T cells that were present in the peripheral blood before rituximab administration treatment rapidly increased after DLI in association with a decrease in the EBV-DNA load. © 2016 Elsevier B.V.Embargo Period 12 month

One-step nucleic acid amplification for intraoperative diagnosis of lymph node metastasis in lung cancer patients: a single-center prospective study

One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer

Overcoming epithelial-mesenchymal transition-mediated drug resistance with monensin-based combined therapy in non-small cell lung cancer

Background The epithelial-mesenchymal transition (EMT) is a key process in tumor progression and metastasis and is also associated with drug resistance. Thus, controlling EMT status is a research of interest to conquer the malignant tumors. Materials and methods A drug repositioning analysis of transcriptomic data from a public cell line database identified monensin, a widely used in veterinary medicine, as a candidate EMT inhibitor that suppresses the conversion of the EMT phenotype. Using TGF-β-induced EMT cell line models, the effects of monensin on the EMT status and EMT-mediated drug resistance were assessed. Results TGF-β treatment induced EMT in non-small cell lung cancer (NSCLC) cell lines and the EGFR-mutant NSCLC cell lines with TGF-β-induced EMT acquired resistance to EGFR-tyrosine kinase inhibitor. The addition of monensin effectively suppressed the TGF-β-induced-EMT conversion, and restored the growth inhibition and the induction of apoptosis by the EGFR-tyrosine kinase inhibitor. Conclusion Our data suggested that combined therapy with monensin might be a useful strategy for preventing EMT-mediated acquired drug resistance

Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand–receptor relationships

AbstractMedaka (Oryzias latipes) is a small freshwater teleost that provides an excellent developmental genetic model complementary to zebrafish. Our recent mutagenesis screening using medaka identified headfish (hdf) which is characterized by the absence of trunk and tail structures with nearly normal head including the midbrain–hindbrain boundary (MHB). Positional-candidate cloning revealed that the hdf mutation causes a functionally null form of Fgfr1. The fgfr1hdf is thus the first fgf receptor mutant in fish. Although FGF signaling has been implicated in mesoderm induction, mesoderm is induced normally in the fgfr1hdf mutant, but subsequently, mutant embryos fail to maintain the mesoderm, leading to defects in mesoderm derivatives, especially in trunk and tail. Furthermore, we found that morpholino knockdown of medaka fgf8 resulted in a phenotype identical to the fgfr1hdf mutant, suggesting that like its mouse counterpart, Fgf8 is a major ligand for Fgfr1 in medaka early embryogenesis. Intriguingly, Fgf8 and Fgfr1 in zebrafish are also suggested to form a major ligand–receptor pair, but their function is much diverged, as the zebrafish fgfr1 morphant and zebrafish fgf8 mutant acerebellar (ace) only fail to develop the MHB, but develop nearly unaffected trunk and tail. These results provide evidence that teleost fish have evolved divergent functions of Fgf8–Fgfr1 while maintaining the ligand–receptor relationships. Comparative analysis using different fish is thus invaluable for shedding light on evolutionary diversification of gene function