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1.
J Nutr Biochem ; : 108871, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34571188

RESUMO

Fucoxanthin (Fx) has shown potential cancer chemopreventive functions in a carcinogenic murine azoxymethane/dextran sodium sulfate (AOM/DSS) model. However, the molecular mechanisms based on transcriptome profiles in vivo remain poorly understood. We investigated Fx-dependent alterations of the transcriptome with cancer-associated proteins in colorectal mucosal tissue obtained from AOM/DSS mice with or without Fx treatment. Fx administration (50 mg/kg body weight for 14 weeks) significantly prevented the onset of colorectal adenocarcinoma in AOM/DSS mice. A transcriptome analysis revealed that 11 signals, including adhesion, cell cycle, chemokine receptor, interleukin, MAPK, PI3K/AKT, p53, RAS, STAT, TGF-ß, and Wnt were remarkably altered by Fx administration. In particular, chemokine (C-C motif) receptor 1 (Ccr1), which is contained in a gene set related to cytokine-cytokine receptor interactions, was the only significantly down-regulated gene after Fx administration for both 7 and 14 weeks. CCR1, AKT, Cyclin D1, and Smad2 were found to play central roles in the 11 signals shown above. Fx administration significantly down-regulated CCR1 (0.3- and 0.5-fold in mucosal crypts and lamina propria, respectively), pAKT(Ser473) (0.2-fold in mucosal crypts), Cyclin D1 (0.4-fold in mucosal crypts), and pSmad2(Ser465/467) (0.7-fold in mucosal crypts) compared with proteins in these tissues of control mice after Fx administration for 14 weeks. Our findings suggested that Fx exerts a chemopreventive effect in AOM/DSS mice through attenuation of CCR1 expression along with 11 cancer-associated signals.

2.
Sci Total Environ ; 800: 149374, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34388645

RESUMO

Benzotriazole UV stabilizers (BUVSs) are added to various materials to prevent damage from UV-irradiation. Recently, there has been great concern regarding the endocrine-disrupting effects of exposure to microplastic-derivative BUVSs in particular. In this study, we measured the concentrations of nine representative BUVSs in the plastic bottle caps of 10 beverages, 4 food packages, and 4 plastic shopping bags purchased from Japanese grocery stores by GC-MS analysis, and found that eight BUVSs, except for 2-(3,5-di-tert-butyl-2-hydroxyphenyl)-2H-benzotriazole (UV-320), were detected from these plastic products. In particular, 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) and 2-(2-hydroxy-3-tert-butyl-5-methylphenyl)-5-chlorobenzotriazole (UV-326) were detected from all the bottle caps at concentrations in the order of ng/g. In addition, we characterized the agonistic and/or antagonistic activities against human estrogen receptors (ERα/ß) and androgen receptor (AR) of 13 BUVSs. Results revealed that, among the 13 BUVSs, UV-P, 2-(5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-PS), 2-[2-hydroxy-5-[2-(methacryloyloxy)ethyl]phenyl]-2H-benzotriazole (UV-090) and 2-(2-hydroxy-5-tert-octylphenyl)-benzotriazole (UV-329) showed ERα and/or ERß agonistic activity, with UV-P being the most potent based on these assays. On the other hand, UV-320 and 2-(3-s-butyl-5-tert-butyl-2-hydroxyphenyl) benzotriazole (UV-350) showed both ERα and ERß antagonistic activities, and 2-(3,5-di-tert-amyl-2-hydroxylphenyl) benzotriazole (UV-328) and UV-329 acted as ERß antagonists. In the AR assay, UV-P and 2-(3-allyl-2-hydroxy-5-methylphenyl)-2H-benzotriazole (UV-9) showed AR antagonistic activity although none of the test compounds showed AR agonistic activity. Taken together, our findings suggest that a series of BUVSs are present in our environments via plastic materials and several of these compounds possess endocrine-disrupting potential, such as ERα/ß agonistic and/or antagonistic activity and AR antagonistic activity. UV-P and its structurally similar compounds, in particular, appear to be a cause for concern.

3.
Drug Metab Pharmacokinet ; 40: 100411, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34284282

RESUMO

The expression of transporters on the apical and basal membranes of renal tubular cells is modulated under acute kidney injury (AKI). However, little is known about alterations in non-renal transporters in the tissues other than the kidney under AKI situation. This study aimed to assess the modulation of organic anion transporting polypeptide (Oatp) 1a2 and Oatp2b1 expression/function in the small intestine of rats with drug-induced AKI. AKI was induced by intraperitoneal administration of cisplatin at a dose of 5 mg/kg. On day 3 after cisplatin administration, morphological changes in the small intestine, Oatp1a2 and Oatp2b1 expression, and absorption of pravastatin and theophylline were evaluated. Non-negligible atrophy was observed in the jejunum and ileum of the AKI rats. However, the absorption of theophylline was not affected. While intestinal Oatp2b1 expression was markedly decreased in the AKI rats, no alteration was observed in Oatp1a2 expression. The plasma levels of pravastatin after intraluminal administration declined significantly in the AKI rats. However, no such decline was observed after intravenous administration. This study suggested that the responses of intestinal Oatps to experimentally induced AKI was not unidirectional and that pravastatin absorption was governed more potently by Oatp2b1 than by Oatp1a2 in the rat intestine.

4.
Sci Rep ; 11(1): 14285, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253746

RESUMO

Pancreatic duct stenting is a well-established method for reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, there is no consensus on the optimal type of plastic stent. This study aimed to evaluate the feasibility and safety of a new 4-Fr plastic stent for pancreatic duct stenting. Forty-nine consecutive patients who placed the 4-Fr stent into the pancreatic duct (4Fr group) were compared with 187 consecutive patients who placed a conventional 5-Fr stent (control group). The primary outcome was technical success. Complications rate, including post-ERCP pancreatitis (PEP) were the secondary outcomes. Propensity score matching was introduced to reduce selection bias. The technical success rate was 100% in the 4Fr group and 97.9% in the control group (p = 0.315). Post-ERCP amylase level was significantly lower in the 4-Fr group than the control group before propensity score matching (p = 0.006), though without statistical significance after propensity score matching (p = 0.298). The rate of PEP in the 4Fr group (6.1%) was lower than the control group (15.5%), though without statistical significance before (p = 0.088) and after (p = 1.00) propensity score matching. Pancreatic duct stenting using a novel 4-Fr plastic stent would be at least similar or more feasible and safe compared to the conventional plastic stent.

5.
Chem Pharm Bull (Tokyo) ; 69(7): 608-611, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193709

RESUMO

The coumarin skeleton has been a focus of attention for many years, and its fluorescence properties vary depending on the substituents. Fluorescent coumarin derivatives are useful tools for many strategies have been developed for their synthesis. Although 7-diethylaminocoumarin has excellent fluorescence properties, it is unstable. We have developed a facile strategy for the synthesis of 7-diethylaminocoumarin derivatives by increasing the electrophilicity of the ynone moiety to promote nucleophilic addition reactions and cyclization. The reaction tolerates a variety of substitutions at the 4-position.


Assuntos
Cumarínicos/química , Ciclização , Elétrons , Corantes Fluorescentes/química , Espectrometria de Fluorescência
6.
Endosc Ultrasound ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34259218

RESUMO

Background and Objectives: EUS-guided biliary drainage (EUS-BD) has recently been used for the treatment of not only malignant pancreaticobiliary diseases, but also for benign diseases. In most previous studies, EUS-BD was performed using a fully covered self-expandable metallic stent (SEMS), and data focusing on the usability of plastic stents for benign diseases are limited. We previously developed a plastic stent dedicated to EUS-guided hepaticoenterostomy (EUS-HES), and achieved favorable results in a feasibility study, although most of the patients had malignant diseases. Therefore, the aim of the present study was to evaluate the usability of dedicated plastic stents for EUS-HES in patients with benign pancreaticobiliary diseases. Patients and Methods: A total of 57 consecutive patients (28 men, median age: 68 years; range: 7-90 years) of normal and surgically altered anatomy with benign pancreaticobiliary diseases who underwent EUS-HES using the dedicated plastic stent between Jan. 2015 and Jun. 2020 were retrospectively analyzed. Results: The overall technical success rate of EUS-HES was 92.9% (53/57). Among the 4 cases of technical failure of plastic stent placement, a SEMS was placed in 1; percutaneous transhepatic biliary drainage was performed in 1; EUS-HES was reperformed 1 week later in 1; and observational management was selected in 1 patient. Adverse events associated with the procedure were seen in 15.7% (9/57) of the patients, namely, biliary peritonitis in 4, bleeding in 2, cholecystitis in 2, and pneumoperitoneum in 1 patient. Except for 1 patient who required blood transfusion owing to bleeding and 1 patient with cholecystitis who required percutaneous transhepatic gallbladder drainage, the other 7 patients were treated by conservative therapy. There were no intervention-associated deaths. Conclusion: Our results demonstrated that for patients with benign pancreaticobiliary diseases in whom conventional ERCP was unsuccessful, EUS-HES using a dedicated plastic stent was safe and feasible.

7.
Toxicol Appl Pharmacol ; 423: 115570, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33965372

RESUMO

The expression of transporters on the apical and basal membranes of renal proximal tubular cells are down- or upregulated to various extents under cisplatin (CDDP)-induced acute kidney injury (AKI). However, little is known about the changes in transporters in tissues other than the kidney under CDDP-induced AKI. This study aimed to investigate the modulation of the expression/function of intestinal efflux transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp), in CDDP-induced AKI rats. On day 3 after the intraperitoneal administration of CDDP (5 mg/kg) to rats, the expression levels of P-gp and Bcrp were compared with those of normal rats. Further, the absorption of three P-gp substrates (6α-methylprednisolone, rhodamine 123, and gatifloxacin) was evaluated in both groups using conventional loop techniques. In the CDDP-induced AKI rats, P-gp expression in the ileum was markedly decreased to approximately 38% of that in the normal rats. However, no significant changes in Bcrp expression were observed in the AKI rats. In contrast with the reduction in P-gp expression in the AKI rats, the absorption of the three P-gp substrates remained almost the same or decreased in the AKI group. The addition of verapamil (a potent P-gp inhibitor) increased the absorption of the three P-gp substrates to the values obtained from the normal rats. In conclusion, our results suggested that P-gp expression is downregulated in rats with CDDP-induced AKI but that P-gp maintains its potency as a "gatekeeper" against the absorption of xenobiotics by amplifying its individual transport capacity under these conditions.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Cisplatino/toxicidade , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/biossíntese , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Injúria Renal Aguda/genética , Animais , Antineoplásicos/toxicidade , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Expressão Gênica , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley
8.
Cancer Genomics Proteomics ; 18(3 Suppl): 407-423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994364

RESUMO

BACKGROUND/AIM: Fucoxanthinol (FxOH) is a marine carotenoid metabolite with potent anti-cancer activity. However, little is known about the efficacy of FxOH in pancreatic cancer. In the present study, we investigated the inhibitory effect of FxOH on six types of cells cloned from N-nitrosobis(2-oxopropyl)amine (BOP)-induced hamster pancreatic cancer (HaPC) cells. MATERIALS AND METHODS: FxOH action and its molecular mechanisms were investigated in HaPC cells using flow-cytometry, comprehensive gene array, and western blotting analyses. RESULTS: FxOH (5.0 µM) significantly suppressed the growth of four out of six types of HaPC cells. Moreover, FxOH significantly suppressed cell cycle, chemokine, integrin, actin polymerization, microtubule organization and PI3K/AKT and TGF-ß signals, and activated caspase-3 followed by apoptosis and anoikis induction in HaPC-5 cells. CONCLUSION: FxOH may have a high potential as a cancer chemopreventive agent in a hamster pancreatic carcinogenesis model.

9.
J Nat Med ; 75(3): 623-632, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33830449

RESUMO

The anti-inflammatory effects of a 50% aqueous extract of Rosa roxburghii fruit (RRFE) and two ellagitannins (strictinin and casuarictin) isolated from the RRFE were evaluated in a cell model of skin inflammation induced by self-RNA released from epidermal cells damaged by UV ray (UVR) irradiation. The RRFE inhibited interleukin-8 (IL-8) mRNA expression in normal human epidermal keratinocytes (NHEKs) stimulated with polyinosinic:polycytidylic acid (poly(I:C)), a ligand of toll-like receptor-3 (TLR-3). The plant-derived anti-inflammatory agents, dipotassium glycyrrhizinate (GK2) and allantoin, had no influence on the IL-8 expression. The purified compounds, strictinin and casuarictin, inhibited the IL-8 mRNA expression and IL-8 release induced in NHEKs by poly(I:C). These ellagitannins were thus found to be responsible for the biological activity exhibited by the RRFE. This study demonstrates that RRFE and isolated RRFE compounds show promise as ingredients for products formulated to improve skin disorders induced by UVR irradiation.


Assuntos
Taninos Hidrolisáveis/farmacologia , Interleucina-8/biossíntese , Queratinócitos/efeitos dos fármacos , Rosa/química , Compostos de Bifenilo , Células Cultivadas , Frutas/química , Ácido Gálico/análogos & derivados , Humanos , Queratinócitos/metabolismo , Fenóis , Poli I-C/farmacologia , Raios Ultravioleta
10.
Nihon Shokakibyo Gakkai Zasshi ; 118(4): 340-347, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33840715

RESUMO

A 57-year-old woman presented with multilocular cysts like a bunch of grapes, 30mm in diameter, in the tail of the pancreas. The number of cysts has increased, and each one had grown. Eventually, they turned into a unilocular cyst with a cyst in the cyst structure of about 50mm in diameter. Laparoscopic distal pancreatectomy was performed, and the resected specimen was diagnosed with mucinous cystadenoma. We report the rare morphological change in this case and consider the mechanism of its occurrence based on pathological considerations.


Assuntos
Cistadenoma Mucinoso , Cistos , Neoplasias Pancreáticas , Cistadenoma Mucinoso/diagnóstico por imagem , Cistadenoma Mucinoso/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pâncreas , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia
11.
Nutr Cancer ; 73(5): 889-898, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33703973

RESUMO

Fucoxanthin is a marine xanthophyll found in edible brown algae, and a metabolite, fucoxanthinol (FxOH), possesses a potent apoptosis inducing effect in many cancer cells. Chloride intracellular channel 4 (CLIC4) is a member of the CLIC family that plays an important role in cancer development and apoptosis. However, the role of CLIC4 in FxOH-induced apoptosis is not well understood. In this study, we investigated whether CLIC4 affects the apoptotic properties of FxOH in human colorectal cancer (CRC) cells under FxOH treatment. Treating human CRC DLD-1 cells with 5.0 µmol/L FxOH significantly induced apoptosis. FxOH downregulated CLIC4, integrin ß1, NHERF2 and pSmad2 (Ser465/467) by 0.6-, 0.7-, 0.7-, and 0.5-fold, respectively, compared with control cells without alteration of Rab35 expression. No colocalizing change was observed in CLIC4-related proteins in either control or FxOH-treated cells. CLIC4 knockdown suppressed cell growth and apoptosis. Interestingly, apoptosis induction by FxOH almost disappeared with CLIC4 knockdown. Our findings suggested that CLIC4 could be involved in FxOH-induced apoptosis in human CRC.


Assuntos
Neoplasias Colorretais , beta Caroteno , Apoptose , Proliferação de Células , Canais de Cloreto , Neoplasias Colorretais/tratamento farmacológico , Humanos , beta Caroteno/análogos & derivados
12.
Anticancer Res ; 41(3): 1299-1305, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788721

RESUMO

BACKGROUND/AIM: A xanthophyll of fucoxanthin (Fx) is a potential chemopreventive agent. Familial adenomatous polyposis (FAP) is an inherited disease that is associated with a high risk of developing colorectal cancer. However, it remains unclear whether Fx can modify colorectal tumorigenesis in ApcMin/+ mice, a model mouse for human FAP. MATERIALS AND METHODS: We investigated the chemopreventive effect of Fx in dextran sodium sulfate (DSS)-treated ApcMin/+ mice. RESULTS: Administration of Fx in the diet for 5 weeks significantly suppressed the number of colorectal adenocarcinomas in DSS-treated male ApcMin/+ mice, although the treatment did not affect the occurrence of colorectal dysplastic crypts and adenoma in the mice. In addition, Fx down-regulated cyclin D1 expression (0.6-fold) in colorectal mucosa of ApcMin/+ mice when compared with that of the control mice. CONCLUSION: Fx possesses chemopreventive potential against progression of colorectal carcinogenesis in ApcMin/+ mice that receive inflammatory stimuli.


Assuntos
Polipose Adenomatosa do Colo/complicações , Anticarcinógenos/administração & dosagem , Neoplasias Colorretais/prevenção & controle , Xantofilas/administração & dosagem , Animais , Neoplasias Colorretais/induzido quimicamente , Ciclina D1/análise , Ciclina D1/fisiologia , Sulfato de Dextrana , Modelos Animais de Doenças , Masculino , Camundongos
13.
Sci Rep ; 11(1): 5990, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727633

RESUMO

Anion exchanger 2 (AE2) plays crucial roles in regulating cell volume homeostasis and cell migration. We found that both IRBIT and Long-IRBIT (L-IRBIT) interact with anion exchanger 2 (AE2). The interaction occurred between the conserved AHCY-homologous domain of IRBIT/L-IRBIT and the N-terminal cytoplasmic region of AE2. Interestingly, AE2 activity was reduced in L-IRBIT KO cells, but not in IRBIT KO cells. Moreover, AE2 activity was slightly increased in IRBIT/L-IRBIT double KO cells. These changes in AE2 activity resulted from changes in the AE2 expression level of each mutant cell, and affected the regulatory volume increase and cell migration. The activity and expression level of AE2 in IRBIT/L-IRBIT double KO cells were downregulated if IRBIT, but not L-IRBIT, was expressed again in the cells, and the downregulation was cancelled by the co-expression of L-IRBIT. The mRNA levels of AE2 in each KO cell did not change, and the downregulation of AE2 in L-IRBIT KO cells was inhibited by bafilomycin A1. These results indicate that IRBIT binding facilitates the lysosomal degradation of AE2, which is inhibited by coexisting L-IRBIT, suggesting a novel regulatory mode of AE2 activity through the binding of two homologous proteins with opposing functions.

14.
Cancer Genomics Proteomics ; 18(2): 133-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33608310

RESUMO

BACKGROUND/AIM: Fucoxanthinol (FxOH), a predominant metabolite from fucoxanthin (Fx), can exert potential anti-cancer effects in various cancers. However, limited data are available on the effect of FxOH or Fx on pancreatic cancer. The present study investigated the effect of FxOH on a cell line derived from pancreatic cancer tissue developed in Ptf1aCre/+; LSL-k-rasG12D/+ mice. MATERIALS AND METHODS: Using flow-cytometric, microarrays, and western blotting analyses, alterations in FxOH-induced apoptosis-related gene expression and protein levels were evaluated in a mice pancreatic cancer cell line, KMPC44. RESULTS: FxOH significantly arrested the cells at S phase along with suppression of many gene sets, such as cytokine- cytokine receptor interaction and cell adhesion molecule CAMS. Moreover, attenuated protein levels for cytokine receptors, adhesion, phosphatidylinositol-3 kinase/protein kinase B, and mitogen-activated protein kinase were observed. CONCLUSION: FxOH may prevent pancreatic cancer development in a murine cancer model.


Assuntos
Carcinoma in Situ/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Apoptose , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , beta Caroteno/análogos & derivados , beta Caroteno/farmacologia
15.
Biosci Biotechnol Biochem ; 85(3): 493-501, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33589895

RESUMO

The Asian traditional medicinal plant Acorus calamus and its component α-asarone exhibited various biological activities, such as antiinflammation and antioxidant effects. In the present study, we investigated the in vitro effects of A. calamus extract and α-asarone on oxidative stress- and endoplasmic reticulum (ER) stress-induced cell death in hippocampal HT22 cells. A. calamus extract and α-asarone both significantly suppressed cell death induced by the oxidative stress inducer l-glutamate and ER stress inducer tunicamycin. A. calamus extract and α-asarone also significantly reduced reactive oxygen species (ROS) production induced by l-glutamate. Moreover, A. calamus extract and α-asarone suppressed the phosphorylation of protein kinase RNA-like ER kinase (PERK) induced by tunicamycin. These results suggest that A. calamus extract and α-asarone protect hippocampal cells from oxidative stress and ER stress by decreasing ROS production and suppressing PERK signaling, respectively. α-Asarone has potential as a potent therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease.


Assuntos
Acorus/química , Derivados de Alilbenzenos/farmacologia , Anisóis/farmacologia , Antibacterianos/farmacologia , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tunicamicina/farmacologia , Animais , Linhagem Celular , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipocampo/citologia , Camundongos , Neurônios/citologia , Fosforilação , Espécies Reativas de Oxigênio/metabolismo
16.
Nutr Cancer ; : 1-16, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33590779

RESUMO

Fucoxanthin and its metabolite fucoxanthinol (FxOH), highly polar xanthophylls, exert strong anticancer effects against many cancer cell types. However, the effects of Fx and FxOH on pancreatic cancer, a high mortality cancer, remain unclear. We herein investigated whether FxOH induces apoptosis in human pancreatic cancer cells. FxOH (5.0 µmol/L) significantly promoted the growth of human pancreatic cancer PANC-1 cells, but induced apoptosis in human colorectal cancer DLD-1 cells. A microarray-based gene analysis revealed that the gene sets of cell cycle, adhesion, PI3K/AKT, MAPK, NRF2, adipogenesis, TGF-ß, STAT, and Wnt signals in PANC-1 cells were markedly altered by FxOH. A western blot analysis showed that FxOH up-regulated the expression of integrin ß1 and PPARγ as well as the activation of pFAK(Tyr397), pPaxillin(Tyr31), and pAKT(Ser473) in PANC-1 cells, but exerted the opposite effects in DLD-1 cells. Moreover, the expression of FYN, a downstream target of integrin subunits, was up-regulated (7.4-fold by qPCR) in FxOH-treated PANC-1 cells. These results suggest that FxOH accelerates the growth of PANC-1 cells by up-regulating the expression of integrin ß1, FAK, Paxillin, FYN, AKT, and PPARγ.

17.
Endosc Ultrasound ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33463555

RESUMO

Background and Objectives: EUS-guided biliary drainage (EUS-BD) has been reported as an effective alternative drainage technique. However, clinical data on EUS-BD for patients with acute cholangitis (AC) are limited. The aim of this study was to analyze the clinical outcomes of EUS-BD in patients with AC. Patients and Methods: Nineteen patients with AC who underwent urgent or early drainage (within 96 h) by EUS-guided hepaticoenterostomy (EUS-HES) between January 2014 and November 2019 were retrospectively reviewed. Furthermore, the clinical outcomes of EUS-HES using a plastic stent in the AC group (n = 15) were compared to those in the non-AC group (n = 88). Results: In the 19 AC cases, the technical and clinical success rate was 100% with 5.3% of moderate adverse events (biliary peritonitis [n = 1]). Regarding the comparison between the AC group and the non-AC group, the clinical success rate was 100% in both groups and the adverse event rate was not statistically significantly different (P = 0.88). Although the recurrent biliary obstruction (RBO) rate was not statistically significantly different (P = 0.43), the early RBO rate was statistically significantly higher in the AC group (26.7% vs. 3.4%, P < 0.001). Kaplan-Meier curves showed that AC was associated with a shorter time to RBO (P = 0.046). The presence of AC was found to be an independent risk factor of early RBO (odds ratio = 10.3; P = 0.005). Conclusions: Urgent or early biliary drainage (within 96 h) by EUS-BD can be a feasible and safe alternative procedure for patients with AC, although there is a tendency of early RBO.

18.
Carcinogenesis ; 42(2): 210-219, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32940665

RESUMO

Fucoxanthin (Fx), a marine carotenoid found in edible brown algae, is well known for having anticancer properties. The gut microbiota has been demonstrated as a hallmark for colorectal cancer progression in both humans and rodents. However, it remains unclear whether the gut microbiota is associated with the anticancer effect of Fx. We investigated the chemopreventive potency of Fx and its effect on gut microbiota in a mouse model of inflammation-associated colorectal cancer (by azoxymethane/dextran sulfate sodium treatment). Fx administration (30 mg/kg bw) during a 14 week period significantly inhibited the multiplicity of colorectal adenocarcinoma in mice. The number of apoptosis-like cleaved caspase-3high cells increased significantly in both colonic adenocarcinoma and mucosal crypts. Fx administration significantly suppressed Bacteroidlales (f_uc; g_uc) (0.3-fold) and Rikenellaceae (g_uc) (0.6-fold) and increased Lachnospiraceae (g_uc) (2.2-fold), compared with those of control mice. Oral administration of a fecal suspension obtained from Fx-treated mice, aimed to enhance Lachnospiraceae, suppress the number of colorectal adenocarcinomas in azoxymethane/dextran sulfate sodium-treated mice with a successful increase in Lachnospiraceae in the gut. Our findings suggested that an alteration in gut microbiota by dietary Fx might be an essential factor in the cancer chemopreventive effect of Fx in azoxymethane/dextran sulfate sodium-treated mice.


Assuntos
Adenocarcinoma/prevenção & controle , Colite Ulcerativa/tratamento farmacológico , Neoplasias Associadas a Colite/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Xantofilas/administração & dosagem , Adenocarcinoma/imunologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologia , Animais , Azoximetano/administração & dosagem , Azoximetano/toxicidade , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Neoplasias Associadas a Colite/imunologia , Neoplasias Associadas a Colite/microbiologia , Neoplasias Associadas a Colite/patologia , Sulfato de Dextrana/administração & dosagem , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Fezes/microbiologia , Microbioma Gastrointestinal/imunologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos
19.
J Hepatobiliary Pancreat Sci ; 28(1): 95-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32910528

RESUMO

BACKGROUND/PURPOSE: The application of artificial intelligence to clinical diagnostics using deep learning has been developed in recent years. In this study, we developed an original computer-assisted diagnosis (CAD) system using deep learning analysis of EUS images (EUS-CAD), and assessed its ability to detect pancreatic ductal carcinoma (PDAC), using control images from patients with chronic pancreatitis (CP) and those with a normal pancreas (NP). METHODS: A total of 920 endosonographic images were used for the training and 10-fold cross-validation, and another 470 images were independently tested. The detection abilities in both the validation and test setting were assessed, and independent factors associated with misdetection were identified among participants' characteristics and endosonographic image features. RESULTS: Regarding the detection ability of EUS-CAD, the areas under the receiver operating characteristic curve were found to be 0.924 and 0.940 in the validation and test setting, respectively. In the analysis of misdetection, no factors were identified on univariate analysis in PDAC cases. On multivariate analysis of non-PDAC cases, only mass formation was associated with overdiagnosis of tumors. CONCLUSIONS: Our pilot study demonstrated the efficacy of EUS-CAD for the detection of PDAC.

20.
In Vivo ; 34(6): 3205-3215, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144425

RESUMO

BACKGROUND/AIM: Fucoxanthin (Fx) is a potent anticancer carotenoid, demonstrated by mouse cancer models. We recently showed the decrease of salivary glycine could represent an attenuation of tumor microenvironment (TME) formation in an azoxymethane/dextran sodium sulfate (AOM/DSS) colon cancer mouse model. However, it remains unclear whether the salivary glycine is an indicator for continuous TME suppression of Fx in the mice. MATERIALS AND METHODS: In the present study, we time-dependently analyzed salivary metabolites in AOM/DSS mice, and investigated candidate markers to evaluate the continuous inhibition of colonic TME formation and carcinogenesis in the mice with and without Fx. RESULTS: Fx attenuated the incidence and/or multiplicity of colonic lesions developed in AOM/DSS mice. The number of apoptosis-like cleaved caspase-3high cells was significantly increased, and colonic cancer stem cell-like CD44high/EpCAMhigh cells and cancer-associated fibroblast-like αSMAhigh cells were significantly decreased in colon mucosal tissue by Fx administration. Salivary glycine at 4, 11 and 14 weeks after the final DSS exposure in the Fx-treated mice showed successful and consecutive decreases of 0.5-, 0.4- and 0.7-fold respectively compared to that of control mice. CONCLUSION: Salivary glycine is a valuable indicator that could evaluate sustained efficacy of cancer chemopreventive effects of Fx in AOM/DSS mice.


Assuntos
Colite , Neoplasias do Colo , Animais , Azoximetano , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Sulfato de Dextrana/toxicidade , Glicina , Camundongos , Microambiente Tumoral , Xantofilas
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