EGF Induces Epithelial-mesenchymal Transition and Cancer Stem-like Cell Properties in Human Oral Cancer Cells via Promoting Warburg Effect

Warburg effect , the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24-population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells

Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study

Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and β-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive.Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, β1, β3, β5, β6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated.Results: We observed immunohistochemical integrin αV, β1, β6, β8, and FAK expressions in the cell membrane and cytoplasm but not integrin β3 and β5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin β8-positive patients with OSCC (p < 0.05). No association between integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was observed.Conclusion: Our results indicate that pFAK and integrin β8 are prognostic factors for OSCC. Therefore, pFAK- and integrin β8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential

Asthma exacerbations after the East Japan Disaster

On March 11, 2011, a 9.0-magnitude earthquake struck east Japan, following tsunami. Many people are forced to live in evacuation shelters without enough life-saving drugs. Asthma control for management of health crisis is required, because asthma exacerbation is a major cause of morbidity, can need acute care and results in death. However, it remains obscure what parameter should be used in primary clinic of evacuation shelters. The objective of this study is to elucidate the practical efficacy of asthma assessment tool in primary clinic for victims of this disaster. Asthma control test (ACT), a brief and patient-based tool to evaluate asthma control, was conducted for 17 patients with asthma in evacuation shelters at Tohoku district. Total sum of ACT scores were significantly decreased after this disaster. Significant decreases were observed for the items ; “Asthma keeps you from getting much done at work”, “Shortness of breath”, “Asthma symptoms wake you up” and “Patient rating of control”. ACT, an easy and practicable tool, clearly demonstrated the asthma exacerbation in evacuation shelters without the use of lung function testing. ACT may contribute to the management of health crisis not only for this East Japan disaster but also for the other forthcoming unavoidable disasters

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

Nanoparticle Deposition of Fluoropolymer CYTOP via Holographic Femtosecond Laser Processing and Its Biochip Application

The fundamental characteristics of nanoparticle (NP) deposition of the fluoropolymer CYTOP using a femtosecond (fs) laser were investigated. In previous studies, we have demonstrated the microfluidic fabrication of CYTOP, which enables clear microscopic observation of the fluid boundary because of its low refractive index, as well as that of water. In the present work, we generated CYTOP NPs using holographic fs laser processing with a spatial light modulator to demonstrate the capabilities of this functional polymer. We established a deposition technique via five-dot parallel fs laser beam irradiation for fibrous network and monolayer structures composed of CYTOP NPs on the surface of glass slides by manipulating the various fundamental laser processing parameters. The network structure on the glass surface exhibits superhydrophobic behavior, while the monolayer structure performs almost the same wettability as that of CYTOP thin film. After an investigation of the surface features of the NPs deposited onto the glass, the combination of the holographic fs laser deposition and the removal of CYTOP NPs was used to selectively pattern CYTOP NPs on the glass slide for HeLa cell culturing. Consequently, cells were selectively cultured on the glass surface where the laser removal of deposited NPs was carried out

DataSheet1_Clinical significance of integrin αV and β superfamily members and focal adhesion kinase activity in oral squamous cell carcinoma: a retrospective observational study.pdf

Objectives: Integrins are heterodimeric transmembrane plasma membrane proteins composed of α- and β-chains. They bind to extracellular matrix (ECM) and cytoskeletal proteins as ECM protein receptors. Upon ECM protein binding, integrins activate focal adhesion kinase (FAK) and transduce various signals. Despite their importance, integrin and FAK expression in oral squamous cell carcinoma (OSCC) tissue and the prognosis of patients with OSCC remains elusive.Methods: In a retrospective observational study, we immunohistochemically evaluated integrin αV, β1, β3, β5, β6, FAK, and phosphorylated-FAK (pFAK) expressions as prognostic predictors in 96 patients with OSCC. Patients were classified as positive or negative based on staining intensity, and clinicopathologic characteristics and survival rates of the two groups were compared. The association between above integrin-related proteins and PD-1 or PD-L1 in OSCC tissues was investigated.Results: We observed immunohistochemical integrin αV, β1, β6, β8, and FAK expressions in the cell membrane and cytoplasm but not integrin β3 and β5 in the OSCC tissues. pFAK was expressed in the cytoplasm of OSCC cells. The overall survival rate significantly decreased in pFAK-positive OSCC patients compared to the negative group, and cervical lymph node metastasis significantly increased in integrin β8-positive patients with OSCC (p Conclusion: Our results indicate that pFAK and integrin β8 are prognostic factors for OSCC. Therefore, pFAK- and integrin β8-targeting new oral cancer diagnostic and therapeutic methods hold a promising potential.</p