The eustachian tube function was investigated in 100 ears of 50 healthy individuals in their 20s to 50s with no ear disease, by inspecting the opening of the eustachian tube (ET) using sonotubometry ...and impedance methods (Valsalva maneuver, Toynbee maneuver, deep breathing, and sniffling). Of the 100 ears, the ET opening was found to be positive patent by sonotubometry in 82.0%, with during the Valsalva maneuver in 82.0%, and with during the Toynbee maneuver in 65.0%, and by all three methods in 51%. In sonotubometry, the duration of tubal opening ranged from 105 to 2,455 msec, with a mean of 569.5 msec. The ET opening was negative closed in a total of 35 ears by sonotubometry or during the Valsalva maneuver, and it was considered that these ears were at a higher risk of middle ear pressure injury. A total of 16 ears showed a “prolonged duration” of opening of more than 1,000 msec, or “movement of the tympanic membrane” during deep breathing or sniffling, and were believed to be at a higher risk of showing a patulous Eustachian tube in the presence of some trigger. It may be necessary to evaluate the ET status comprehensively based on a subject's symptoms, physical findings, and results of multiple ET function tests.
Aqua-Line bus fares have been reduced. In the city of Kisarazu, the number of commuters to central Tokyo, Kawasaki, and Yokohama has increased, and most use highway buses. The population of Kisarazu ...has increased, especially in the suburbs, and large-scale shopping centers such as the AEON Mall have opened in cooperation with the government, with clusters of chain stores around them. As a result, the shopping environment of Kisarazu has improved. However, profits have declined for private shops in the city center. There are few supermarkets and drugstores, and it is difficult to purchase daily necessities. AEON operates a free shuttle bus, which is used by older people. Kisarazu’s population distribution and commerce are based on the use of cars. As relations with AEON and the aging of the region progress, the ease of shopping and securing means of transportation have become an issue.
Background
The heterotopic submucosal gland (HSG) is a common incidental finding in gastrectomy specimens. The majority of HSGs are small incidental lesions, which are also known as gastritis cystica ...profunda. However, larger lesions may appear as an inverted growth of well-organized mucosa referred to as gastric inverted polyps.
Methods
To determine whether genetic alterations are involved in HSG development, we analyzed 63 gastric HSG lesions using targeted next-generation sequencing and immunohistochemistry.
Results
Histologically, HSG lesions consistently had areas of pyloric gland differentiation with variable extent of foveolar differentiation. Although the background mucosa showed intestinal metaplasia in most cases (98%), intestinal-type epithelium was seen in only one HSG lesion (2%). Sequencing analysis identified activating
KRAS
,
BRAF
,
CTNNB1
, and
GNAS
mutations in 34 (54%), 1 (2%), 1 (2%), and 7 (11%) lesions, respectively. HSG lesions harboring a
KRAS
mutation were more likely to present extensive foveolar differentiation (
P
= 0.013) and absence of parietal cells (
P
= 0.0081). Five HSG lesions had a dysplastic component, and concordant genetic alterations were detected between the non-dysplastic and dysplastic areas of two lesions that were successfully analyzed. Immunohistochemical staining demonstrated diffuse expression of mutant KRAS protein in lesions with the most common genetic alteration,
KRAS
G12D.
Conclusions
Our study demonstrated that a major proportion of HSGs were proliferative lesions associated with oncogenic mutations, with more than half of lesions harboring activating
KRAS
mutations.
Background
Traditional serrated adenoma (TSA) is the least common type of colorectal serrated polyp, which exhibits considerable morphological and molecular diversity.
Methods
We examined the spectra ...of alterations in MAPK and WNT pathway genes and their relationship with clinicopathological features in 128 TSAs.
Results
Sequencing analyses identified
BRAF
V600E,
BRAF
non-V600E,
KRAS
, and
NRAS
mutations in 77, 3, 45, and 1 lesion, respectively. Collectively, 124 lesions (97%) had mutations in MAPK pathway genes. Alterations in WNT pathway genes were identified in 107 lesions (84%), including
RSPO
fusions/overexpression,
RNF43
mutations,
ZNRF3
mutations,
APC
mutations, and
CTNNB1
mutations in 47, 45, 2, 13, and 2 lesions, respectively. Ten lesions (8%) harbored
GNAS
mutations. There was significant interdependence between the altered MAPK and WNT pathway genes.
RSPO
fusions/overexpression was significantly associated with
KRAS
mutations (31/47, 66%), whereas most
RNF43
mutations coexisted with the
BRAF
V600E mutation (40/45, 89%). Histologically, extensive slit-like serration was more common in lesions with the
BRAF
V600E mutation (71%) and those with
RNF43
mutations (87%). Prominent ectopic crypt formation was more prevalent in lesions with
RSPO
fusions/overexpression (58%) and those with
GNAS
mutations (100%).
Conclusions
Our observations indicate that TSAs mostly harbor various combinations of concurrent WNT and MAPK gene alterations. The associations between genetic and morphological features suggest that the histological diversity of TSA reflects the underlying molecular heterogeneity.
Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, can confer aggressive properties to cancer cells by secreting multiple factors. Their phenotypes are stably maintained, but ...the mechanisms are not fully understood. We aimed to show the critical role of epigenetic changes in CAFs in maintaining their tumour-promoting capacity and to show the validity of the epigenomic approach in identifying therapeutic targets from CAFs to starve cancer cells.
Twelve pairs of primary gastric CAFs and their corresponding non-CAFs (NCAFs) were established from surgical specimens. Genome-wide DNA methylation and H3K27me3 analyses were conducted by BeadArray 450K and ChIP-on-Chip, respectively. Functions of potential a therapeutic target were analysed by inhibiting it, and prognostic impact was assessed in a database.
CAFs had diverse and distinct DNA methylation and H3K27me3 patterns compared with NCAFs. Loss of H3K27me3, but not DNA methylation, in CAFs was enriched for genes involved in stem cell niche, cell growth, tissue development and stromal-epithelial interactions, such as
,
,
and
. Among these, we revealed that WNT5A, which had been considered to be derived from cancer cells, was highly expressed in cancer stromal fibroblasts, and was associated with poor prognosis. Inhibition of secreted WNT5A from CAFs suppressed cancer cell growth and migration.
H3K27me3 plays a crucial role in defining tumour-promoting capacities of CAFs, and multiple stem cell niche factors were secreted from CAFs due to loss of H3K27me3. The validity of the epigenetic approach to uncover therapeutic targets for cancer-starving therapy was demonstrated.
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