Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in PC9 Cells

IntroductionNicotine, the major component among the 4000 identified chemicals in cigarette smoke, binds to nicotinic acetylcholine receptors (nAChRs) on non–small-cell lung cancer (NSCLC) cells and regulates cellular proliferation by activating mitogen-activated protein kinases [AQ: MAPK has been expanded to mitogen-activated protein kinases. Please approve.]and PI3K/Akt pathways. In patients with smoking-related lung cancer who continue smoking, the anticancer effect of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is weaker than that in nonsmokers; however, the precise reason for this difference remains unclear. We investigated the role of α1 nAChR subunit in this phenomenon.MethodsWe screened for α1 nAChR mRNA in three NSCLC cell lines and analyzed the protein in resected primary NSCLC tissues. We used Western blot and RNA interference (siRNA) methodology to confirm the results.ResultsWe determined that α1 nAChR plays an essential role in nicotine-induced cell signaling and nicotine-induced resistance to EGFR-TKI. In addition, we showed that silencing of α1 nAChR subunit in NSCLC may suppress the nicotine-induced resistance to EGFR-TKI.ConclusionsThese results further implicate nicotine in lung carcinogenesis, and suggest that α1 nAChR may be a biomarker for EGFR-TKI treatment and also a personalizing target molecule for patients with smoking-related lung cancer

The Possible Role of TASK Channels in Rank-Ordered Recruitment of Motoneurons in the Dorsolateral Part of the Trigeminal Motor Nucleus.

Because a rank-ordered recruitment of motor units occurs during isometric contraction of jaw-closing muscles, jaw-closing motoneurons (MNs) may be recruited in a manner dependent on their soma sizes or input resistances (IRs). In the dorsolateral part of the trigeminal motor nucleus (dl-TMN) in rats, MNs abundantly express TWIK (two-pore domain weak inwardly rectifying K channel)-related acid-sensitive-K(+) channel (TASK)-1 and TASK3 channels, which determine the IR and resting membrane potential. Here we examined how TASK channels are involved in IR-dependent activation/recruitment of MNs in the rat dl-TMN by using multiple methods. The real-time PCR study revealed that single large MNs (>35 μm) expressed TASK1 and TASK3 mRNAs more abundantly compared with single small MNs (15-20 μm). The immunohistochemistry revealed that TASK1 and TASK3 channels were complementarily distributed in somata and dendrites of MNs, respectively. The density of TASK1 channels seemed to increase with a decrease in soma diameter while there were inverse relationships between the soma size of MNs and IR, resting membrane potential, or spike threshold. Dual whole-cell recordings obtained from smaller and larger MNs revealed that the recruitment of MNs depends on their IRs in response to repetitive stimulation of the presumed Ia afferents. 8-Bromoguanosine-cGMP decreased IRs in small MNs, while it hardly changed those in large MNs, and subsequently decreased the difference in spike-onset latency between the smaller and larger MNs, causing a synchronous activation of MNs. These results suggest that TASK channels play critical roles in rank-ordered recruitment of MNs in the dl-TMN

Gingival Nikolsky’s Sign: A Valuable Tool in Identifying Oral Manifestations of Mucous Membrane Pemphigoid and Pemphigus Vulgaris

Autoimmune bullous diseases are a group of rare, chronic blistering diseases that affects the skin and mucous membranes. Mucous membrane pemphigoid (MMP) is the most frequently occurring autoimmune bullous disease in the oral cavity, followed by pemphigus vulgaris (PV). Early diagnosis of MMP or PV is critical for proper management and prevention of potential serious complications. This study was based on a retrospective review of 39 cases that were classified as MMP (25 patients) or PV (14 patients). Nikolsky’s sign characterized by epithelial detachment as a result of slight pressure or rubbing the oral mucosa is a simple test that can confirm the existence of gingival desquamation. A positive reaction was confirmed in 38 patients (97.4%) at their first visit. This result indicates that patients showing positive Nikolsky’s sign should include MMP or PV in the differential diagnosis and, in that case, histopathological examination and direct immunofluorescence testing are critical to establish the final diagnosis. For the early diagnosis of autoimmune bullous disorders, oral healthcare providers should consider the use of the test for Nikolsky’s sign that may ultimately lead to the early diagnosis of MMP and PV or other diseases or disorders

Desquamative Gingivitis: Early Sign of Mucous Membrane Pemphigoid and Pemphigus Vulgaris

Early signs and symptoms of autoimmune bullous diseases such as mucous membrane pemphigoid (MMP) or pemphigus vulgaris (PV) develop in the oral cavity in almost all cases. Desquamative gingivitis (DG) is a clinical manifestation common to several diseases or disorders and is frequently associated with autoimmune bullous diseases. This is a retrospective study of 37 patients with MMP (24 cases) or PV (13 cases) including 10 males and 27 females with a mean age of 58.4 years. The study indicates that DG is an early sign of autoimmune bullous diseases such as MMP or PV. About 70.3% of the oral lesions were confined only to the gingiva, and DG was the only manifestation of the diseases. Since some lesions remain limited to the oral cavity for a long period of time, patients diagnosed with MMP or PV should be closely followed because they must be immediately referred to other experts when they develop lesions on parts of their body other than the oral cavity. The oral healthcare provider should collaborate with other healthcare experts including dermatologists, ophthalmologists, and otolaryngologists to evaluate and manage patients with autoimmune bullous diseases in the oral cavity

Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications

To clarify the role of CD8+ effector T cells for infectious complications, 92 recipients were classified according to the hierarchical clustering of preoperative CD8+CD45 isoforms: Group I was naive, Group II was effector memory, and Group III was effector (E) T cell-dominant. The posttransplant infection rates progressively increased from 29% in Group I to 64.3% in Group III recipients. The posttransplant immune status was compared with the pretransplant status, based on the measure (% difference) and its graphical form (scatter plot). In Groups I and II, both approaches showed a strong upward deviation from pretransplant status upon posttransplant infection, indicating an enhanced clearance of pathogens. In Group III, in contrast, both approaches showed a clear downward deviation from preoperative status, indicating deficient cytotoxicity. The % E difference and scatter plot can be used as a useful indicator of a posttransplant infectious complication

Biological responses according to the shape and size of carbon nanotubes in BEAS-2B and MESO-1 cells

This study aimed to investigate the influence of the shape and size of multi-walled carbon nanotubes (MWCNTs) and cup-stacked carbon nanotubes (CSCNTs) on biological responses in vitro. Three types of MWCNTs - VGCF (R)-X, VGCF (R)-S, and VGCF (R) (vapor grown carbon fibers; with diameters of 15, 80, and 150 nm, respectively) - and three CSCNTs of different lengths (CS-L, 20-80 mu m; CS-S, 0.5-20 mu m; and CS-M, of intermediate length) were tested. Human bronchial epithelial (BEAS-2B) and malignant pleural mesothelioma cells were exposed to the CNTs (1-50 mu g/mL), and cell viability, permeability, uptake, total reactive oxygen species/superoxide production, and intracellular acidity were measured. CSCNTs were less toxic than MWCNTs in both cell types over a 24-hour exposure period. The cytotoxicity of endocytosed MWCNTs varied according to cell type/size, while that of CSCNTs depended on tube length irrespective of cell type. CNT diameter and length influenced cell aggregation and injury extent. Intracellular acidity increased independently of lysosomal activity along with the number of vacuoles in BEAS-2B cells exposed for 24 hours to either CNT (concentration, 10 mu g/mL). However, total reactive oxygen species/superoxide generation did not contribute to cytotoxicity. The results demonstrate that CSCNTs could be suitable for biological applications and that CNT shape and size can have differential effects depending on cell type, which can be exploited in the development of highly specialized, biocompatible CNTs.ArticleINTERNATIONAL JOURNAL OF NANOMEDICINE. 9:1979-1990 (2014)journal articl