AbstractBenign nasal septal tumors are rare and exhibit various histologic features. It is necessary to treat them based on a plan that considers the prognosis, functionality, and esthetics. We ...report two similar and rare cases of nasal septal tumors with different diagnoses that we treated with nasal septal tumor resection. Eosinophilic angiocentric disease was the most likely diagnosis of one of the two cases, but it was not confirmed by the IgG4:IgG ratio. The other case was diagnosed as extranodal Rosai-Dorfman disease based on its histological features. The histological appearance of nasal septal tumors varies widely; therefore, a careful diagnosis based on both clinical and pathological perspectives is required.
We studied the thermal behavior and curing process of a cyanate ester resin (Cy)/epoxy resin (EP)/thermal latent polymeric hardener system based on a phenol–amine salt (PA-hardener) and the resulting ...cross-linked structure. Additionally, the physical properties of the cured product were evaluated. As a result, the curing system of Cy/EP with the PA-hardener was found to have unique thermal behavior, and an adhesion process was conducted in which the functionality and reactivity of the cyanate ester resin were utilized. The system cured rapidly at approximately 80 °C and could be completely cured at 120 °C in 1 h because the PA-hardener dissolved in the resins at an elevated temperature to give free amines, which could readily initiate the polymerization of cyanate ester resins and epoxy resins. The glass-transition temperature (T g) of the cured products increased with increasing a triazine-rich cross-linked structure derived from the cyclotrimerization of the cyanate ester resin as the curing proceeded at a relatively low temperature. The Cy/EP/PA-hardener system was found to have a rapid curing process and excellent adhesiveness, and it afforded a cured product with heat stability.
This report describes a cost-effective experimental method for determining an intrinsically disordered protein (IDP) region in a given protein sample. In this area, the most popular (and ...conventional) means is using the amide (
H
) NMR signal chemical shift distributed in the range of 7.5-8.5 ppm. For this study, we applied an additional step: analysis of
H
chemical shift temperature coefficients (
H
-CSTCs) of the signals. We measured
H-
N two-dimensional NMR spectra of model IDP samples and ordered samples at four temperatures (288, 293, 298, and 303 K). We derived the
H
-CSTC threshold deviation, which gives the best correlation of ordered and disordered regions among the proteins examined (below -3.6 ppb/K). By combining these criteria with the newly optimized chemical shift range (7.8-8.5 ppm), the ratios of both true positive and true negative were improved by approximately 19% (62-81%) compared with the conventional "chemical shift-only" method.
Introduction. Hypomethylating agents azacitidine (AZA) and decitabine are standard of care for myelodysplastic syndromes (MDS). Considering the result of the secondary analysis of the AZA-001 trial ...showing 91% of first responses occurred within 6 cycles, the concept is widely accepted that AZA should be performed at least 6 cycles even if early response is not achieved (Silverman LR, Cancer. 2011). However, 40-50% of cases finally experienced primary resistance. These facts mean almost half of the patients receive fruitless treatment for up to six months. Therefore, it is necessary to identify those patients who do not response to AZA from the early cycles, so that they can receive alternative treatment as early as possible.
The Wilms' tumor 1 gene (WT1) is a tumor marker of leukemic blasts. High expression of WT1-mRNA is correlated with disease progression, efficacy of AZA and prognosis in the patients with MDS (Tamaki et al, Leukemia. 1999). In this study, we explored whether WT1-mRNA levels in peripheral blood (PB) samples at baseline and during the early cycles of AZA could be useful in predicting outcome to this therapy.
Methods. We retrospectively evaluated transplant-ineligible patients with high-risk MDS, diagnosed according to the 2008 World Health Organization classification, who received more than three cycles of AZA as a 1st line therapy between March 2012 and January 2020 at Aiiku Hospital and Sapporo Hokuyu Hospital. Response to treatment was classified as complete remission (CR), partial remission (PR), hematologic improvement (HI), stable disease, and failure based on the International Working Group 2006 criteria. Patients who were not evaluated WT1-mRNA levels in PB samples at baseline and within three cycles of AZA were excluded from this study. WT1-mRNA was measured using a WT1-mRNA Assay Kit (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan). The study procedures were in accordance with the Helsinki Declaration and institutional ethical guidelines, and were approved by the institutional review boards.
Results. Seventy-five patients (age 61-88, median 77; 76% male) were included in this study. The median follow-up time from AZA initiation was 11.4 months (range, 4.2-48.8 months). Median overall survival (OS) time from AZA initiation was 16.4 months (95% CI, 11.6-24.1 months). Forty-one patients (54.7%) achieved any response (CR + PR + HI). WT1-mRNA expression at the baseline varied from <50 to 320000 copies/µg RNA (median, 3400 copies/µg RNA). We classified them into four groups based on the dynamics of PB WT1-mRNA levels within three cycles of AZA, with a threshold of the median level for the definition of “high” or “low” WT1-mRNA levels. Low-increase (LI) group included patients with low WT1-mRNA level at baseline and elevated to high level with 2 times or more than the baseline. Low-stable (LS) group included cases with initial WT1-mRNA level low but did not meet the LI criteria. High-decrease (HD) group included patients with initial WT1-mRNA level high and decreased to less than half of it. High-stable (HS) group included cases with initial WT1-mRNA level high but did not meet the HD criteria. Six patients were included in the LI, 32 patients in LS, 21 patients in HD, and 16 patients in HS. The median number of AZA cycles in LS/HD was 11 (range, 3-34 cycles), while in HS/LI was 7 (range, 3-17 cycles). Cumulative incidence of any response after 10 cycles of AZA was significantly higher in LS/HD than in HS/LI (75.5% vs 4.5%, P=0.00000028; Gray test, Figure A). For LS/HD, the median OS was 18.2 months (95% CI, 12.8-28.1 months), whereas HS/LI had a median OS of 11.6 months (95% CI, 6.6-14.1 months; P=0.00995; Log-rank, Figure B). A multivariate analysis demonstrated that Poor/Very poor International Prognostic Scoring System (IPSS-R) cytogenetic risk and HS/LI were independently associated with poor outcome (OS; Poor/Very poor IPSS-R cytogenetic risk; HR, 2.33; 95% CI, 1.24 to 4.38, P=0.0087, HS/LI; HR, 2.46; 95% CI, 1.31 to 4.61, P=0.0052; Cox regression analysis). Altogether, we demonstrated that dynamic change of PB WT1-mRNA within three cycles of AZA predicts response for AZA and prognosis in patients with high-risk MDS.
Conclusion. Dynamic change of PB WT1-mRNA within three cycles of AZA was correlated with response for AZA in patients with high-risk MDS. Moreover, patients in HS/LI could not get any further response by continuous cycles of AZA and should be considered for alternative options.
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Teshima:Takeda Pharmaceutical Company Limited: Consultancy, Honoraria; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Merck: Consultancy, Honoraria; Sharp & Dohme Corp: Consultancy, Honoraria; Sanofi K.K.: Research Funding; TEIJIN PHARMA LIMITED: Honoraria; Chugai Pharmaceutical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; The Center of Innovation Program from Japan Science and Technology Agency: Other; Japan Society for the Promotion of Science KAKENHI (17H04206): Other; Janssen Pharmaceutical K.K.: Other; NIPPON SHINYAKU CO., LTD.: Honoraria; Fuji Pharma Co., Ltd.: Honoraria; Novartis Pharma K.K.: Consultancy, Other: Manuscript preparation, Research Funding; Bristol-Myers Squibb: Honoraria; Pfizer Japan Inc.: Honoraria.
Primary malignant melanoma of the esophagus (PMME) is a very rare malignancy accounting for only 0.1% to 0.2% of all malignant esophageal lesions. Presently, there are no standard strategies or clear ...guidelines for PMME treatment.
Herein, we report a patient who had PMME with multiple lymph node metastases (LNMs) who was treated successfully by esophagectomy. In March 2018, a 74-year-old man with symptoms of continuous dysphagia was referred to our hospital.
Upper gastrointestinal endoscopic examination revealed melanin pigmentation in the middle thoracic esophagus and a pigmented polypoid mass in the lower esophagus. Histopathological examination of the endoscopic biopsy specimen revealed malignant melanoma. Contrast-enhanced computed tomography showed a 3 cm tumor lesion with several enlarged lymph nodes without distant metastasis. The preoperative diagnosis based on the TNM classification was cT2N2M0 stage III.
The patient underwent esophagectomy with lymph node dissection.
Histopathological examination showed that the tumor extended to the submucosal layer of the esophageal wall, with multiple LNMs. Although multiple LNMs were detected, computed tomography scan 15 months after surgery showed no recurrence. Additionally, we analyzed the relationship between the overall survival and the clinicopathological factors including LNMs in 48 previously reported cases of PMME that were surgically treated.
To our knowledge, this is the first report on the effect of LNMs on the prognosis of PMME patients. The analysis revealed the prognostic value of the TNM stage. Early tumor detection and esophagectomy with lymph node dissection may play as key factors for achieving a better overall survival of PMME patients.
Tumor suppressor cylindromatosis (CYLD) dysfunction by its downregulation is significantly associated with poor prognosis in patients with glioblastoma (GBM), the most aggressive and malignant type ...of glioma. However, no effective treatment is currently available for patients with CYLD-downregulated GBM. The aim of the present study was to identify the crucial cell signaling pathways and novel therapeutic targets for CYLD downregulation in GBM cells. CYLD knockdown in GBM cells induced GBM malignant characteristics, such as proliferation, metastasis, and GBM stem-like cell (GSC) formation. Comprehensive proteomic analysis and RNA sequencing data from the tissues of patients with GBM revealed that Wnt/β-catenin signaling was significantly activated by CYLD knockdown in patients with GBM. Furthermore, a Wnt/β-catenin signaling inhibitor suppressed all CYLD knockdown-induced malignant characteristics of GBM. Taken together, the results of the present study revealed that Wnt/β-catenin signaling is responsible for CYLD silencing-induced GBM malignancy; therefore, targeting Wnt/β-catenin may be effective for the treatment of CYLD-negative patients with GBM with poor prognosis.
Bone tissue is a composite material consisting of hydroxyapatite and collagen. It is known that bone tissue becomes brittle with age not only because of decreased bone density but also because of ...excessive apatite deposition in the tissue. Demineralization provides a means for changing the mechanical properties of bone. Although demineralization decreases the elastic modulus of bone tissue, it also increases the flexible deformation compliance of the tissue. Previous studies have shown that localized demineralization around the areas of stress concentration in cortical bone specimens can improve impact fracture toughness despite reducing the stiffness. Demineralization is usually performed via chemical reactions in solution. This method is not suitable for limited demineralization at specific areas because of the infiltration and outflow of the solution. In this study, we focus on reactions induced by electric stimulation and investigate the possibility of demineralization by applying voltage. X-ray diffraction was used to verify the demineralization progression. The absence of apatite peaks in the X-ray diffraction pattern of the bone specimen after voltage application shows that demineralization has occurred after this treatment. To investigate the relationship between the electrode shape and the demineralized area, the hardness distribution on the surface of specimen was measured via multiple-point micro-indentation tests. The impact fracture characteristics in the limited areas demineralized by voltage application were measured through Charpy loading tests. As a result, it was found that the demineralization was accelerated at the contact area of the electrode to specimen surface during the voltage application. And it was suggested that the limited demineralization may improve the fracture strength of the bone tissue.
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