CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma.

BackgroundCytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC.MethodsExpression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses.ResultsFirst, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples.ConclusionsCYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model

PURPOSETo compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model.METHODSTwenty-seven Sprague–Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups.RESULTSThe non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48–79) vs. 55 (37–70), P = 0.003; 1 (0–2) vs. 1 (0–2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56–83.90%) vs. 16.34 (3.22–32.0%), P < 0.001].CONCLUSIONPVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol

Product Development Activities Using Ingredients from Nagasaki Prefecture～Impact on local activities and response to the spread of new coronavirus infection～

application/pdf長崎短期大学 地域共生学科 製菓コースでは、平成25 年度より長崎県の特産品を使用した商品開発活動を続けている。令和元年度までは、試食会や販売等を通して地域の方と交流する活動の1つであったが、令和2年度以降、新型コロナウイルス感染症蔓延により他者と接触は大きな制限を伴い、令和２年度4月よりオンライン・オンデマンド授業が開始し、令和３年度～令和４年度に関しても同様に学生の学びの活動は制約を受けることになった。商品開発活動は、キャップストーン科目としての役割を果たすため、新たな取り組みを行った活動内容を記録したものである。departmental bulletin pape

Gastrointestinal Stromal Tumor of the Stomach with Narrow Stalk-Like Based, Uneven Protruding Appearance Presenting with Severe Acute Anemia despite Small Size

We report the case of a 56-year-old woman who had a gastrointestinal stromal tumor (GIST) of the stomach. She was admitted to our hospital for epigastric pain, nausea, and severe acute anemia (hemoglobin level 4.3 g/dl). Esophagogastroduodenoscopy revealed a narrow stalk-like based, hemorrhagic and uneven protruding lesion in the lesser curvature of the gastric upper corpus. Although the tumor was less than 2 cm in diameter and was probably a benign GIST according to histology, laparoscopy-assisted local resection was needed because the patient had continuous severe anemia and epigastric pain. Histological assessment showed that the elongated spindle-like tumor cells originated from the intrinsic muscle layer, and was shown with growth to the mucosal side, cropping out to the surface in most areas of the protruding lesion. Only a small part of the tumor was within nontumoral gastric mucosa. Most of the tumor cells demonstrated immunoreactivity for KIT and CD34 in the cytoplasm but not for αSMA, S100, and desmin. Mitotic activity (0/50 high power field) and the labeling index for MIB-1 (about 1%) were low. The GIST of the stomach described in this report was a rare case with a narrow stalk-like based, uneven protruding mass presenting with severe acute anemia despite small size

A Genetic Variant of the CD14 C-159T in Patients with Functional Dyspepsia (FD) in Japanese Subjects

Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the relationship between the genetic regulatory factors of inflammation and FD are not available. CD14 is an important mediator of the inflammatory response in the first line of host defense by recognition of Lipopolysaccharide (LPS). We aimed to investigate the association between CD14 promoter C-159T polymorphism and FD in a Japanese population. 108 patients with FD and 99 non-dyspeptic subjects enrolled in this study. Dyspeptic symptoms were divided according to Rome III criteria. CD14 gene C-159T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. In the non-dyspeptics, the CD14 genotype distribution was 28CC (28.3%), 51CT (51.5%), 21TT (21.2%). Meanwhile, the CD14 genotype distribution in FD was 31CC (28.4%), 56CT (51.4%), 22TT (20.2%). The genotype distribution was not significantly different. There was no significant difference between two groups in the genotype distribution. We did not found any association between CD14 genotypes and dyspeptic patients in different gender and Helicobacter pylori infection status. No significant association was also found between CD14 polymorphism and any of different subtypes of FD according to Rome III while there was a weak correlation between TT genotype and PDS in male subjects (TT vs others, OR = 3.18, 95% CI = 0.98−10.26, p = 0.06). In conclusion, our results suggest that CD14 polymorphism is unlikely to associate with susceptibility of dyspeptic symptoms. The role of inflammation related-gene polymorphisms to the development of dyspepsia needs to further evaluation

Correlation between magnifying narrow band imaging and histopathology in gastric protruding/or polypoid lesions: a pilot feasibility trial

<p>Abstract</p> <p>Background</p> <p>Several study showed usefulness of microscopic capillaries, seen by magnifying narrow band imaging (NBI) endoscopy for predicting histopathology among superficial depressed or flat elevated gastric neoplasia (GN). Here we assessed the diagnostic efficacy of magnifying NBI for predicting histopathology among gastric protruding/or polypoid lesions.</p> <p>Methods</p> <p>Using endoscopic pictures of magnifying NBI from 95 protruding/or polypoid lesions (19 fundic gland polyps: FGP, 47 hyperplastic polyps: HP, and 29 GN), fine mucosal patterns were classified into four categories: small round, prolonged, villous or ridge, and unclear patterns, and micro vascular patterns were classified into five categories: honey comb, dense vascular, fine net work, core vascular, and unclear patterns.</p> <p>Results</p> <p>Most suggestive micro vascular patterns for predicting FGP, and HP were honeycomb (sensitivity 94.7%, specificity 97.4%), and dense vascular patterns (sensitivity 93.6%, specificity 91.6%), respectively. Fine net work, core vascular, and unclear patterns presented higher specificity (97%, 100%, and 100%) for predicting GN, and diagnostic efficacy of combined of those patterns was favorable (sensitivity 86.2%, specificity 97.0%).</p> <p>Conclusion</p> <p>Micro vascular patterns by using magnifying NBI provides meaningful information for predicting the histopathology of gastric protruding/or polypoid lesions.</p

Editorial: Conflicts

The Editorial Board reflects on the theme of 'conflict', as observed in the work published in this issue, and in the wider world

BHLHA15-Positive Secretory Precursor Cells Can Give Rise to Tumors in Intestine and Colon in Mice

Background & Aims: The intestinal epithelium is maintained by long-lived intestinal stem cells (ISCs) that reside near the crypt base. Above the ISC zone, there are short-lived progenitors that normally give rise to lineage-specific differentiated cell types but can dedifferentiate into ISCs in certain circumstances. However, the role of epithelial dedifferentiation in cancer development has not been fully elucidated. Methods: We performed studies with Bhlha15-CreERT, Lgr5-DTR-GFP, Apc flox/flox , LSL-Notch (IC), and R26-reporter strains of mice. Some mice were given diphtheria toxin to ablate Lgr5-positive cells, were irradiated, or were given 5-fluorouracil, hydroxyurea, doxorubicin, or dextran sodium sulfate to induce intestinal or colonic tissue injury. In intestinal tissues, we analyzed the fate of progeny that expressed Bhlha15. We used microarrays and reverse-transcription PCR to analyze gene expression patterns in healthy and injured intestinal tissues and in tumors. We analyzed gene expression patterns in human colorectal tumors using The Cancer Genome Atlas data set. Results: Bhlha15 identified Paneth cells and short-lived secretory precursors (including pre-Paneth label-retaining cells) located just above the ISC zone in the intestinal epithelium. Bhlha15 + cells had no plasticity after loss of Lgr5-positive cells or irradiation. However, Bhlha15 + secretory precursors started to supply the enterocyte lineage after doxorubicin-induced epithelial injury in a Notch-dependent manner. Sustained activation of Notch converts Bhlha15 + secretory precursors to long-lived enterocyte progenitors. Administration of doxorubicin and expression of an activated form of Notch resulted in a gene expression pattern associated with enterocyte progenitors, whereas only sustained activation of Notch altered gene expression patterns in Bhlha15 + precursors toward those of ISCs. Bhlha15 + enterocyte progenitors with sustained activation of Notch formed intestinal tumors with serrated features in mice with disruption of Apc. In the colon, Bhlha15 marked secretory precursors that became stem-like, cancer-initiating cells after dextran sodium sulfate–induced injury, via activation of Src and YAP signaling. In analyses of human colorectal tumors, we associated activation of Notch with chromosome instability-type tumors with serrated features in the left colon. Conclusions: In mice, we found that short-lived precursors can undergo permanent reprogramming by activation of Notch and YAP signaling. These cells could mediate tumor formation in addition to traditional ISCs

Is Estrogen Effective for Full-Thickness Cutaneous Wound Healing in Young Male Mice ?

The aim of this study is to show the effects of estrogen upon its topical application on the wound healing process in young male mice. Fifty-six male mice aged 7 weeks old were divided into 4 groups: sham operation, castration, estrogen treatment after sham operation, and estrogen treatment after castration. Wound healing was observed daily until day 14 after wounding. Specimens were harvested on days 3, 7, 10, and 14, and stained to evaluate reepithelialization, inflammation, contraction, and collagen accumulation. Wound healing periods of all groups were almost the same, although the concentration of serum estrogen in the estrogen-applied mice was very high, and that in the nonapplied groups was low. The numbers of macrophages in the castrated, estrogen-treated after sham operation, and estrogen-treated after castration groups were significantly decreased compared with that in the sham group in the inflammatory phase; however, the ratio of wound area in these groups did not decrease, and other histological data did not reveal any effects of estrogen. These results indicate that estrogen may show limited effectiveness for full-thickness cutaneous wound healing in young male mice, and decreased inflammation may not always be associated with decreased wound area