Summary Medullary carcinoma (MC) of the colorectum is known as a rare variant with favorable prognosis despite its poorly differentiated morphology. The mechanism of its favorable behavior has been ...unclear. Here, we compared the expressions of adhesion molecules and epithelial-mesenchymal transition (EMT)–related proteins in the central portion and invasive front between 43 MCs and 30 poorly differentiated adenocarcinomas (PDAs). The expressions of membranous E-cadherin ( P < .0001), β -catenin ( P < .0001) and claudin 1 ( P = .0036) were significantly preserved in the invasive front of the MCs compared to those in the invasive front of the PDAs. E-cadherin membranous expression was also significantly preserved in the central portion of the MCs ( P = .0178). Nuclear β -catenin expression in both the central portion ( P = .0463) and invasive front ( P = .0346) of the MCs was significantly less frequent compared to that in the PDAs. Snail ( P = .0035) and Twist1 ( P = .0463) expressions in the invasive front of the MCs were significantly less frequent compared to the PDAs, suggesting that the EMT phenomenon may occur rarely in colorectal MC. Reduced membranous E-cadherin expression in the MC central portion was significantly correlated with poor clinical outcome ( P = .0086). Our immunohistochemical results indicate that preserved adhesion molecule protein and less frequent expression of EMT-related transcription factors in the invasive front contribute to the favorable prognosis of colorectal MCs. We suggest that a reduced expression of E-cadherin in the central portion might be a good biomarker for an unfavorable prognosis in cases of MC.
In the steel refining process, dissolution of quick-lime would accompany the formation of 2CaO·SiO2 on its surface. For proper understanding of heat supply to the lime phase from the molten slag ...through this 2CaO·SiO2 layer, thermal conductivity of this phase should be well known. The present study investigates the thermal conductivity of 2CaO·SiO2 bearing solid solution by hot-wire and hot-strip methods. Thermal conductivity of the solid solution was obtained to have the value from 0.28 to 1.18 W/m·K at temperatures from 298 to 1623 K and found much smaller than that of CaO. Its temperature dependence was positive as is often characterized for complex oxide system. Addition of FeO as solid solution component to 2CaO·SiO2 phase raised thermal conductivity and effect of change in concentration of P2O5 was also elucidated to have a minimum peak of thermal conductivity appearing with this change. On the basis of the thermal conductivity of 2CaO·SiO2 obtained and that of CaO, thermal behavior of practical process has been evaluated. The complete thermal decomposition time of CaCO3 contained by 4 mass% in the sphere of quick lime having the radius of 1 cm is estimated to be about 30 s. The appropriate control of residual ratio of CaCO3 and size of quick-lime would be necessary for the promotion of lime dissolution into the steelmaking slag.
A 66-year-old man was referred to our hospital for further evaluation of a polypoid lesion of the stomach detected on radiographic examination. Esophagogastroduodenoscopy revealed a broad-based ...elevated lesion (24mm) with a relatively steep but smooth surface and submucosal tumor-like morphology in the upper body of the stomach, with an edematous red apex and a shallow ulcer. Endoscopic ultrasonography revealed a lesion of low echogenicity with multiple aechoic images in the mucosal-submucosal layers, and we performed endoscopic resection using a snare followed by circumferential incision and submucosal dissection using ESD techniques. Histopathological examination of the resected specimen revealed that the polypoid lesion was composed of submucosal proliferation of cystically dilated gastric glands and fibromuscular elements. Based on these findings, we diagnosed the tumor as a hamartomatous inverted polyp (HIP). Only six cases (including the current case) of HIP with ulceration have been reported in Japan, which indicates the rarity of this form of HIP. The atypical ulcer observed in this case of HIP was probably attributable to mechanical stimulation. HIP is rare and is known to be complicated by cancer. Therefore, preoperative diagnosis is invariably challenging, and it is important to carefully devise the optimal treatment strategy.
In the original version of this Article, the abbreviation of 3,4-dihydroxyphenylacetaldehyde synthase presented in the first paragraph of the Discussion section was given incorrectly as DYPAA. The ...correct abbreviation for this enzyme is DHPAAS. This error has been corrected in both the PDF and HTML versions of the Article.
Background & Aims
Mixed neuroendocrine–non‐neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non‐neuroendocrine components. Although the ...coexistence pattern of neuroendocrine and non‐neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract.
Methods
From 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals.
Results
Among the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ.
Conclusions
These findings suggested a potential “paratransformation” or “bystander effect” in resident epithelium by NENs. Thus, “bystander carcinogenesis” could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract.
All superficial carcinomatous components adjacent to neuroendocrine neoplasms were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ. Therefore, bystander carcinogenesis could be a pathogenic mechanism of resident epithelium transformation adjacent to neuroendocrine neoplasms in the esophagogastrointestinal tract.
The lower esophageal sphincter (LES) plays an important role in coordinated esophageal motility. The present study aimed to elucidate how trypsin affects LES contractility. Porcine LES circular ...smooth muscle strips were prepared. Contractile responses to trypsin were assessed. Trypsin (300nM) induced a transient contraction. At concentrations of 1μM or higher, trypsin induced biphasic responses, consisting of a transient contraction followed by a transient relaxation. Pretreatment with either 1μM tetrodotoxin or carbenoxolone had no effect on these responses. In contrast, trypsin-induced responses were completely blocked by pretreatment with the serine protease inhibitor. Pretreatment with 10μM FSLLRY-NH2, a PAR2 antagonist, significantly inhibited trypsin-induced biphasic responses. Trypsin (1μM)-induced contractions were partially inhibited by pretreatment with 10μM Y-27632. In addition, trypsin (10μM)-induced relaxation was partially inhibited by pretreatment with 10μM Y-27632, 10μM PD98059 or 10μM SB203580. Trypsin-induced relaxation was abolished by increasing the extracellular K+ concentration to 40mM, but not by pretreatment with l-arginine methyl ester. Furthermore, trypsin-induced relaxation was partially inhibited by pretreatment with 10μM glibenclamide or 1μM 4-aminopyridine. Trypsin causes biphasic regulation of LES tone by directly acting on smooth muscle. Rho-associated protein kinase (ROK) is involved in trypsin-induced contraction, whereas ROK, ERK1/2, p38MAPK, and membrane hyperpolarization are involved in relaxation. The regulation of LES tone by trypsin may play a role in esophageal motility.
Saccharomyces cerevisiae is exposed to freeze-thaw stress in commercial processes, including frozen dough baking. Cell viability and fermentation activity after a freeze-thaw cycle were dramatically ...decreased due to freeze-thaw injury. Because this type of injury involves complex phenomena, the injury mechanisms are not fully understood. We examined freeze-thaw injury by indirect gene expression analysis during postthaw incubation after freeze-thaw treatment using DNA microarray profiling. The results showed that genes involved in the homeostasis of metal ions were frequently contained in genes that were upregulated, depending on the freezing period. We assessed the phenotype of deletion mutants of the metal ion homeostasis genes that exhibited freezing period-dependent upregulation and found that the strains with deletion of the MAC1 and CTR1 genes involved in copper ion homeostasis exhibited freeze-thaw sensitivity, suggesting that copper ion homeostasis is required for freeze-thaw tolerance. We found that supplementation with copper ions during postthaw incubation increased intracellular superoxide dismutase activity and intracellular levels of reactive oxygen species were decreased. Moreover, cell viability was increased by supplementation with copper ions. These results suggest that insufficiency of copper ion homeostasis may be one of the causes of freeze-thaw injury.
Effects of a negative supercoil on the local denaturation of the DNA double helix were studied at the single-molecule level. The local denaturation in λDNA and λDNA containing the SV40 origin of DNA ...replication (SV40ori-λDNA) was directly observed by staining single-stranded DNA regions with a fusion protein comprising the ssDNA binding domain of a 70-kDa subunit of replication protein A and an enhanced yellow fluorescent protein (RPA-YFP) followed by staining the double-stranded DNA regions with YOYO-1. The local denaturation of λDNA and SV40ori-λDNA under a negative supercoil state was observed as single bright spots at the single-stranded regions. When negative supercoil densities were gradually increased to 0, −0.045, and −0.095 for λDNA and 0, −0.047, and −0.1 for SV40ori-λDNA, single bright spots at the single-stranded regions were frequently induced under higher negative supercoil densities of −0.095 for λDNA and −0.1 for SV40ori-λDNA. However, single bright spots of the single-stranded regions were rarely observed below a negative supercoil density of −0.045 and −0.047 for λDNA and SV40ori-λDNA, respectively. The probability of occurrence of the local denaturation increased with negative superhelicity for both λDNA and SV40ori-λDNA.
To clarify the value of contrast-enhanced harmonic ultrasonography (US) with Sonazoid, a second-generation US contrast agent, in the differential diagnosis of liver tumors compared to dynamic CT.
A ...total of 249 hepatic nodules in 214 patients were studied; these included 177 hepatocellular carcinomas (HCCs), 42 liver metastases, 20 liver hemangiomas, 6 dysplastic nodules and 4 focal nodular hyperplasias (FNHs). After the injection of Sonazoid, nodules were scanned using real-time contrast-enhanced harmonic US in the vascular phases, i.e. the early and late vascular phases, and the Kupffer phase.
Six enhancement patterns were identified to be significant for the differential diagnosis of hepatic tumors. In HCCs, the presence of intratumoral vessels supplied from the periphery and fast washout (sensitivity, 96.6%; specificity, 94.4%) were the most typical characteristics. In metastases, the presence of rim-like enhancement with peripheral tumor vessels (sensitivity, 88.1%; specificity, 100%) was the typical pattern. In hemangiomas, the presence of intratumoral hypoperfusion images with globular or cotton wool-like pooling, which continue to the late vascular phase (sensitivity, 90.0%; specificity, 99.6%), was typical. In dysplastic nodules, the presence of portal enhancement without arterial supply in the early vascular phase and the presence of intratumoral uptake in the Kupffer phase (sensitivity, 83.3%; specificity, 100%) were the most typical patterns. In FNHs, the presence of a spoke-wheel pattern in the early vascular phase with dense staining in the late vascular phase, and positive uptake within the nodule in the Kupffer phase (sensitivity, 100%; specificity, 100%) were the most typical patterns.
Contrast-enhanced harmonic US with Sonazoid allowed intimate vascular and Kupffer imaging and, therefore, is useful for the differential diagnosis of hepatic tumors.
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