Predicting osimertinib‐treatment outcomes through EGFR mutant‐fraction monitoring in the circulating tumor DNA of EGFR T790M‐positive patients with non‐small cell lung cancer (WJOG8815L)

The WJOG8815L phase II clinical study involves patients with non‐small cell lung cancer (NSCLC) that harbored the EGFR T790M mutation, which confers resistance to EGFR tyrosine kinase inhibitors (TKIs). The purpose of this study was to assess the predictive value of monitoring EGFR genomic alterations in circulating tumor DNA (ctDNA) from patients with NSCLC that undergo treatment with the third‐generation EGFR‐TKI osimertinib. Plasma samples of 52 patients harboring the EGFR T790M mutation were obtained pretreatment (Pre), on day 1 of treatment cycle 4 (C4) or cycle 9 (C9), and at diagnosis of disease progression or treatment discontinuation (PD/stop). CtDNA was screened for EGFR‐TKI‐sensitizing mutations, the EGFR T790M mutation, and other genomic alterations using the cobas EGFR Mutation Test v2 (cobas), droplet digital PCR (ddPCR), and targeted deep sequencing. Analysis of the sensitizing—and T790M—EGFR mutant fractions (MFs) was used to determine tumor mutational burden. Both MFs were found to decrease during treatment, whereas rebound of the sensitizing EGFR MF was observed at PD/stop, suggesting that osimertinib targeted both T790M mutation‐positive tumors and tumors with sensitizing EGFR mutations. Significant differences in the response rates and progression‐free survival were observed between the sensitizing EGFR MF‐high and sensitizing EGFR MF‐low groups (cutoff: median) at C4. In conclusion, ctDNA monitoring for sensitizing EGFR mutations at C4 is suitable for predicting the treatment outcomes in NSCLC patients receiving osimertinib (Clinical Trial Registration No.: UMIN000022076).

Abbreviations

CIs

confidence intervals

ctDNA

circulating tumor DNA

ddPCR

droplet digital PCR

EGFR

epidermal growth factor receptor

MFs

mutant fractions

NGS

next‐generation sequencing

NSCLC

non‐small cell lung cancer

ORR

overall response rate

OS

overall survival

PD

progressive disease

PFS

progression‐free survival

PR

partial response

SD

stable disease

TKI

tyrosine kinase inhibitor

     

Measurement of bite force variables related to human discrimination of left-right hardness differences of silicone rubber samples placed between the incisors

This study was designed to examine human subjects' ability to discriminate between spatially different bite pressures. We measured actual bite pressure distribution when subjects simultaneously bit two silicone rubber samples with different hardnesses using their right and left incisors. They were instructed to compare the hardness of these two rubber samples and indicate which was harder (right or left). The correct-answer rates were statistically significant at P < 0.05 for all pairs of different right and left silicone rubber hardnesses. Simultaneous bite measurements using a multiple-point sheet sensor demonstrated that the bite force, active pressure and maximum pressure point were greater for the harder silicone rubber sample. The difference between the left and right was statistically significant (P < 0.05) for all pairs with different silicone rubber hardnesses. We demonstrated for the first time that subjects could perceive and discriminate between spatially different bite pressures during a single bite with incisors. Differences of the bite force, pressure and the maximum pressure point between the right and left silicone samples should be sensory cues for spatial hardness discrimination.     

A comparative morphologic study of Carabelli cusp between Chinese and Japanese students.]

The study of teeth,dentition and occlusion is helpful to guide oral medical clinic and the study of anthropology.Our department of Osaka Dental University and had many items of research work about teeth,dentition and occlusion between Chinese and Japanese students.This article reports the study of Carabelli cusp.The results revealed:(1)the rate of Carabelli cusp is higher in Japanese than in Chinese and is higher in male than in female.(2)the rate of Carabelli cusp of the first maxillary molar of both side is very high.(3)The rate of Carabelli cusp is related to the height and the type of cusp numbers.These all illustrated the occurence of Carabeiil cusp were influenced by race, individual and the development of teeth.     

Proliferative response of gingival cells to ultrasonic and/or vibration toothbrushes

PURPOSE: To evaluate the effects of ultrasonic and/or vibration toothbrushes on cell proliferation and collagen synthesis. METHODS: In eight dogs, teeth and gingivae were stimulated once a day as follows: the first quadrant with an ultrasonic toothbrush (1.6 MHz); the second one with a mechanical vibratory toothbrush (141 Hz); and the third one with a toothbrush generating both the ultrasound and the vibration. The fourth quadrant served as a control. Proliferative activity and collagen synthesis of gingival cells were evaluated by assaying the expression of proliferating cell nuclear antigen (PCNA) and procollagen type I C-peptide (PIP), respectively. RESULTS: After 5 weeks, ultrasonic or vibratory toothbrushes increased the numbers of PCNA-positive fibroblasts and PIP-positive fibroblasts. Toothbrushing with a combination of ultrasound and mechanical vibration increased the numbers of PIP-positive fibroblasts, total fibroblasts and vascular endothelial cells to a greater extent than the one with only ultrasound alone. Vibratory toothbrush, but not the ultrasonic one, induced an increase in collagen density without gingival overgrowth.     

Effects of ethanol consumption on periodontal inflammation in rats

Studies suggest a correlation between ethanol consumption and periodontal disease. We hypothesized that elevated levels of blood reactive oxygen species following ethanol consumption may increase inflammation in periodontal tissue. Rats were divided into 4 groups (6-7 rats/group). Two groups were fed an ethanol-containing liquid diet, and 2 groups were fed a pair-fed control diet. In one of each dietary group, periodontitis was ligature-induced, while the other group was left unligated. Chronic ethanol feeding alone decreased the ratio of reduced/oxidized glutathione and increased 8-hydroxydeoxy-guanosine and tumor necrosis factor (TNF)-alpha levels in the gingiva. Blood hydroperoxides were also increased. In ligature-induced periodontitis lesions, ethanol feeding enhanced polymorpho-nuclear leukocyte infiltration and TNF-alpha expression. The results suggest that chronic alcohol consumption increased periodontal inflammation, oxidative damage, and TNF-alpha production and had an additive effect on polymorphonuclear leukocyte infiltration and gingival oxidative damage, increasing the severity of periodontal inflammation in the ligature model.