Japanese cedar (JC) pollinosis is a common allergic rhinitis in Japan. JC pollen sublingual immunotherapy (SLIT) tablets are licensed for the treatment of JC pollinosis.
To assess the ...disease-modifying effects of JC pollen SLIT tablets over 5 years (2014-2019), comprising a 3-year treatment period and 2-year follow-up.
A total of 1042 patients with JC pollinosis (aged 5-64 years) were included in the study. An optimal dose-finding study was performed in the first 15 months, after which 240 patients in the placebo (P) group and 236 patients in the optimal active dose (A) group (5000 Japanese allergy units) were re-randomized to receive P or A for an additional 18 months (designated AA, AP, PA, and PP groups). Clinical efficacy was evaluated by the total nasal symptom and medication score (TNSMS) during the peak symptom period of each JC pollen season over 3 years of treatment and 2 years of observation after treatment cessation.
The AA, AP, and PA groups exhibited significantly reduced TNSMS; however, the largest relative reduction was seen in the AA group both during the treatment period (third season, 46.3% vs PP, P < .001) and during the 2-year follow-up period (fourth and fifth seasons, 45.3% and 34.0% vs PP, respectively; P < .001). The most common adverse drug reactions were mild reactions at the administration site.
JC pollen SLIT tablets show sustained clinical efficacy during 3 years of treatment and sustained disease-modifying effects for at least 2 years after treatment cessation.
Chronic rhinosinusitis is a common disease of the nasal cavity and is classified into two major endotypes, which are neutrophilic and eosinophilic. Some patients with neutrophilic and eosinophilic ...chronic rhinosinusitis are refractory to treatment, and the mechanism of drug resistance is not completely understood.
Nasal polyp samples were collected from patients with non-eosinophilic chronic rhinosinusitis (nECRS) and eosinophilic chronic rhinosinusitis (ECRS). Transcriptomic and proteomic analyses were performed simultaneously. Gene Ontology (GO) analysis was conducted to extract genes involved in drug resistance. Then, GO analysis results were validated via real-time polymerase chain reaction and immunohistochemistry analysis.
The nasal polyps of patients with ECRS were enriched with 110 factors in the genes and 112 in the proteins, unlike in those of patients with nECRS. GO analysis on the combined results of both showed that the factors involved in extracellular transportation were enriched. Our analysis focused on multidrug resistance protein 1–5 (MRP1–5). Real-time polymerase chain reaction revealed that the MRP4 expression was significantly upregulated in ECRS polyps. Immunohistochemical staining showed that the MRP3 and MRP4 expressions significantly increased in nECRS and ECRS, respectively. MRP3 and MRP4 expressions were positively correlated with the number of neutrophil and eosinophil infiltrates in polyps and associated with the tendency to relapse in patients with ECRS.
MRP is associated with treatment resistance and is expressed in nasal polyps. The expression pattern had different features based on chronic rhinosinusitis endotype. Therefore, drug resistance factors can be associated with therapeutic outcomes.
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Abstract Purpose To evaluate the efficacy of carbon ion radiotherapy for head-and-neck cancer in a phase II clinical trial. Materials and methods Between April 1997 and February 2006, 236 patients ...with locally advanced, histologically proven, and new or recurrent cancer of the head and neck were treated with carbon ions. The treatment dose was 64.0 GyE/16 fractions/4 weeks (or 57.6 GyE/16 fractions/4 weeks when the wide-range skin was included in the target volume). Results There were grade 3 acute skin reactions in 6% and grade 3 acute mucosal reactions in 10% with no acute reactions worse than grade 3, and grade 2 late skin reactions in 3% and grade 2 late mucosal reactions in 2% with no late reactions worse than grade 2. The 5-year local control rate, by histological type, was 75% for the 85 patients with malignant melanoma, 73% for the 69 with adenoid cystic carcinoma, 73% for the 27 with adenocarcinoma, 61% for the 13 with papillary adenocarcinoma, 61% for the 12 with squamous cell carcinoma and 24% for the 14 with sarcomas. The 5-year over-all survival rate was 68% for adenoid cystic carcinoma, 56% for adenocarcinoma and 35% for malignant melanoma. Conclusions Carbon ion radiotherapy for head and neck cancer showed the therapeutic effectiveness for malignant melanoma and adenoid cystic carcinoma without severe morbidity of the normal tissues.
In spite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall survival rate for patients with head and neck squamous cell carcinoma (HNSCC) ...is very poor (only 15-45%). Understanding the molecular mechanisms of metastatic pathways underlying HNSCC using currently available genomic approaches might improve therapies for and prevention of the disease. Our previous studies showed that three tumor-suppressive microRNAs (miRNAs), miR-26a/b, miR-29a/b/c and miR-218, significantly inhibited cancer cell migration and invasion. Therefore, we hypothesized that these miRNAs-regulated target genes deeply contributed to cancer metastasis. These tumor-suppressive miRNAs directly regulate LOXL2 expression in HNSCC cells by using in silico analysis and luciferase reporter assays. Overexpressed LOXL2 was confirmed in HNSCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in HNSCC cell lines. Our present data showed that tumor-suppressive miRNAs regulation of LOXL2 will provide new insights into the novel molecular mechanisms of HNSCC metastasis.
microRNAs (miRNAs) are responsible for fine tuning the normal expression of RNA networks in human cells. Accumulating studies have demonstrated that abnormally expressed miRNAs have pivotal roles in ...the development of head and neck squamous cell carcinoma (HNSCC). Specifically, expression signatures of miRNAs in HNSCC have revealed dysregulated production of miRNAs and the resultant abnormal production of mRNAs and proteins. In this review, we discuss current findings regarding aberrantly expressed miRNAs and their contribution to HNSCC molecular pathogenesis.
Analysis of the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) based on RNA sequencing showed that dual strands of pre‑miR‑145 (miR‑145‑5p, guide strand; and ...miR‑145‑3p, passenger strand) were significantly reduced in cancer tissues. In miRNA biogenesis, passenger strands of miRNAs are degraded and have no biological activities in cells. The aims of this study were to investigate the functional significance of the passenger strand of miR‑145 and to identify miR‑145‑3p‑regulated oncogenic genes in HNSCC cells. Expression levels of miR‑145‑5p and miR‑145‑3p were significantly downregulated in HNSCC tissues and cell lines (SAS and HSC3 cells). Ectopic expression of miR‑145‑3p inhibited cancer cell proliferation, migration and invasion, similar to miR‑145‑5p, in HNSCC cells. Myosin 1B (MYO1B) was directly regulated by miR‑145‑3p, and knockdown of MYO1B by siRNA inhibited cancer cell aggressiveness. Overexpression of MYO1B was confirmed in HNSCC clinical specimens by analysis of protein and mRNA levels. Interestingly, high expression of MYO1B was associated with poor prognosis in patients with HNSCC by analysis of The Cancer Genome Atlas database (p=0.00452). Our data demonstrated that the passenger strand of miR‑145 acted as an antitumor miRNA through targeting MYO1B in HNSCC cells. The involvement of dual strands of pre‑miR‑145 (miR‑145‑5p and miR‑145‑3p) in the regulation of HNSCC pathogenesis is a novel concept in present RNA research.
MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules consisting of 19-22 nucleotides that are involved in a variety of biological processes, including development, differentiation, ...apoptosis and cell proliferation. In cancer research, a growing body of evidence has indicated that miRNAs are aberrantly expressed in many types of human cancers and can function either as tumor suppressors or oncogenes. Bioinformatic predictions suggest that miRNAs regulate more than 30% of protein-coding genes. Aberrant expression of miRNAs in cancer cells causes destruction of miRNA-regulated messenger RNA networks. Therefore, the identification of miRNA-regulated cancer pathways is important for understanding the molecular mechanisms of human cancer. Searching for the aberrant expression of miRNAs in cancer cells is the first step in the functional analysis of miRNAs in cancer cells. Genome-wide miRNA expression signatures can rapidly and precisely reveal aberrant expression of miRNA in cancers. The miRNA expression signatures of human cancers have revealed that miR-375 is significantly downregulated in cancer cells. Our recent data on maxillary sinus, hypopharyngeal and esophageal squamous cell carcinomas have suggested that miR-375 is frequently downregulated and functions as a tumor suppressor that targets several oncogenic genes in cancer cells. In this review, we focus on several types of human squamous cell carcinoma and describe the aberrant expression of miRNAs and the cancer pathways they regulate in these diseases.
Anaphylaxis is a potentially fatal severe systemic hypersensitivity reaction that causes symptoms in multiple organs such as the skin, respiratory tract, and gastrointestinal tract; however, no ...nationwide epidemiological survey on anaphylaxis has been conducted in Japan. This survey aimed to elucidate the triggers and treatment of anaphylaxis in Japan.
Between February 2015 and October 2017, we prospectively collected clinical data on the triggers and treatment of patients who developed anaphylaxis or were admitted to the emergency room with anaphylaxis in the training and teaching facilities of the Japanese Society of Allergology.
This study included 79 of the 451 affiliated facilities (18%), and a total of 767 patients were enrolled; 73% of them were aged <18 years and 7% had in-hospital triggers. The most common triggers were food (68%), drugs (12%), food-dependent exercise-induced anaphylaxis (5%), insects (4%), and oral immunotherapy (3%), with drugs being the most common in-hospital trigger and food being the most common out-of-hospital trigger. Intramuscular injection of adrenaline was administered therapeutically to 38% of the patients, with 10% requiring multiple doses. Adrenaline auto-injectors were used in 12% of out-of-hospital patients.
The present survey revealed the most common triggers and treatments for anaphylaxis in Japan. Self-management and adrenaline administration as first-line treatment may not be done sufficiently. Therefore, it is necessary to thoroughly educate and train patients and physicians about anaphylaxis.
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