RESUMO
BACKGROUND: The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years. METHODS: Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated. RESULTS: The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment. CONCLUSION: After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future.
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Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Idoso de 80 Anos ou mais , Masculino , Feminino , Estudos Retrospectivos , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Tóquio , Pirróis/uso terapêutico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/uso terapêutico , Japão/epidemiologiaRESUMO
BACKGROUND Texture and color enhancement imaging (TXI), a new type of image-enhanced endoscopy, may improve the detection of gastrointestinal lesions. Barrett's esophagus (BE) requires an accurate diagnosis since it may undergo neoplastic transformation. We aimed to evaluate the usefulness of TXI compared with white light imaging (WLI) in BE. MATERIAL AND METHODS In this prospective study at a single hospital from February 2021 to February 2022, we enrolled 52 consecutive patients with BE. Endoscopic images of BE using WLI, TXI mode 1 (TXI-1), TXI mode 2 (TXI-2), and narrow-band imaging (NBI) were compared by 10 endoscopists (5 experts and 5 trainees). Endoscopists scored visibility for the images as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Total visibility scores for all 10 endoscopists, and subgroups composed of the 5 expert endoscopists and the 5 trainee endoscopists, were evaluated. Main-group (10 endoscopists) scores of ≥40, 21-39, and ≤20, and subgroup (5 endoscopists) scores of ≥20, 11-19, and ≤10, were considered "improved", "equivalent", and "decreased", respectively. Inter-rater reliability (intra-class correlation coefficient [ICC]) was calculated and images were objectively assessed based on L*a*b* color values and color differences (ΔE*). RESULTS All 52 cases were diagnosed as short-segment BE (SSBE). TXI-1/TXI-2 improved visibility compared with WLI was: 78.8%/32.7% for all endoscopists; 82.7%/40.4% for trainees; and 76.9%/34.6% for experts. NBI did not improve visibility. The ICC for TXI-1 and TXI-2 compared with WLI was "excellent" for all endoscopists. The ΔE* between esophageal and Barrett's mucosae, and between Barrett's and gastric mucosae, was higher for TXI-1 than for WLI (P<0.01, P<0.05, respectively). CONCLUSIONS TXI, especially TXI-1, improves the endoscopic diagnosis of SSBE compared with WLI, regardless of the endoscopist's skill.
Assuntos
Esôfago de Barrett , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Transformação Celular Neoplásica , Aumento da ImagemRESUMO
BACKGROUND AND AIM: Magnifying endoscopy (ME) diagnostic algorithm for early gastric cancer (EGC) relies on qualitative features such as microvascular (MV) architecture and microsurface structure; however, it is a "static" diagnostic algorithm that uses still images. ME can visualize red blood cell flow within subepithelial microvessels in real time. Here, we evaluated the utility of using the MV blood flow rate in combination with ME for the diagnosis of EGC as a retrospective study. METHODS: Patients with differentiated-type EGC (n = 10) or patchy redness (n = 10) underwent ME with blue laser imaging. The mean MV blood flow rates of EGC, patchy redness, and background mucosa were calculated by the mean movement distance of one tagging red blood cell using split images of ME with blue laser imaging videos. We compared the mean MV blood flow rate between EGC, patchy redness, and background mucosa and also calculated the MV blood flow imaging ratio (inside lesion/background mucosa) between EGC and patchy redness. RESULTS: Mean MV blood flow rate was significantly lower in EGC (1481 µm/s; range 1057-1762) than in patchy redness (3859 µm/s; 2435-5899) or background mucosa (4140.6 µm/s; 2820-6247) (P < 0.01). The MV blood flow imaging ratio was significantly lower in EGC (0.39; 0.27-0.62) than in patchy redness (0.90; 0.78-1.1) (P < 0.01). CONCLUSIONS: Dynamic diagnosis with MV blood flow rate using ME may be useful for the differential diagnosis of EGC and patchy redness. Endoscopic assessment of dynamic processes within the gastric mucosa may facilitate the diagnosis of EGC.
Assuntos
Neoplasias Gástricas , Gastroscopia , Humanos , Microcirculação , Imagem de Banda Estreita , Projetos Piloto , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagemRESUMO
BACKGROUND AND AIM: Magnifying endoscopy with narrow-band imaging (ME-NBI) has made a huge contribution to clinical practice. However, acquiring skill at ME-NBI diagnosis of early gastric cancer (EGC) requires considerable expertise and experience. Recently, artificial intelligence (AI), using deep learning and a convolutional neural network (CNN), has made remarkable progress in various medical fields. Here, we constructed an AI-assisted CNN computer-aided diagnosis (CAD) system, based on ME-NBI images, to diagnose EGC and evaluated the diagnostic accuracy of the AI-assisted CNN-CAD system. METHODS: The AI-assisted CNN-CAD system (ResNet50) was trained and validated on a dataset of 5574 ME-NBI images (3797 EGCs, 1777 non-cancerous mucosa and lesions). To evaluate the diagnostic accuracy, a separate test dataset of 2300 ME-NBI images (1430 EGCs, 870 non-cancerous mucosa and lesions) was assessed using the AI-assisted CNN-CAD system. RESULTS: The AI-assisted CNN-CAD system required 60 s to analyze 2300 test images. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CNN were 98.7%, 98%, 100%, 100%, and 96.8%, respectively. All misdiagnosed images of EGCs were of low-quality or of superficially depressed and intestinal-type intramucosal cancers that were difficult to distinguish from gastritis, even by experienced endoscopists. CONCLUSIONS: The AI-assisted CNN-CAD system for ME-NBI diagnosis of EGC could process many stored ME-NBI images in a short period of time and had a high diagnostic ability. This system may have great potential for future application to real clinical settings, which could facilitate ME-NBI diagnosis of EGC in practice.
Assuntos
Inteligência Artificial , Detecção Precoce de Câncer/métodos , Endoscopia Gastrointestinal/métodos , Imagem de Banda Estreita/métodos , Redes Neurais de Computação , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: With more prevalent gastroesophageal reflux disease comes increased cases of Barrett's esophagus and esophageal adenocarcinoma. Image-enhanced endoscopy using linked-color imaging (LCI) differentiates between mucosal colors. We compared LCI, white light imaging (WLI), and blue LASER imaging (BLI) in diagnosing reflux esophagitis (RE). METHODS: Consecutive RE patients (modified Los Angeles [LA] classification system) who underwent esophagogastroduodenoscopy using WLI, LCI, and BLI between April 2017 and March 2019 were selected retrospectively. Ten endoscopists compared WLI with LCI or BLI using 142 images from 142 patients. Visibility changes were scored by endoscopists as follows: 5, improved; 4, somewhat improved; 3, equivalent; 2, somewhat decreased; and 1, decreased. For total scores, 40 points was considered improved visibility, 21-39 points was comparable to white light, and < 20 points equaled decreased visibility. Inter- and intra-rater reliabilities (Intra-class Correlation Coefficient [ICC]) were also evaluated. Images showing color differences (ΔE*) and L* a* b* color values in RE and adjacent esophageal mucosae were assessed using CIELAB, a color space system. RESULTS: The mean age of patients was 67.1 years (range: 27-89; 63 males, 79 females). RE LA grades observed included 52 M, 52 A, 24 B, 11 C, and 3 D. Compared with WLI, all RE cases showed improved visibility: 28.2% (40/142), LA grade M: 19.2% (10/52), LA grade A: 34.6% (18/52), LA grade B: 37.5% (9/24), LA grade C: 27.3% (3/11), and LA grade D: 0% (0/3) in LCI, and for all RE cases: 0% in BLI. LCI was not associated with decreased visibility. The LCI inter-rater reliability was "moderate" for LA grade M and "substantial" for erosive RE. The LCI intra-rater reliability was "moderate-substantial" for trainees and experts. Color differences were WLI: 12.3, LCI: 22.7 in LA grade M; and WLI: 18.2, LCI: 31.9 in erosive RE (P < 0.001 for WLI vs. LCI). CONCLUSION: LCI versus WLI and BLI led to improved visibility for RE after subjective and objective evaluations. Visibility and the ICC for minimal change esophagitis were lower than for erosive RE for LCI. With LCI, RE images contrasting better with the surrounding esophageal mucosa were more clearly viewed.
Assuntos
Esôfago de Barrett , Esofagite Péptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Esofagite Péptica/diagnóstico por imagem , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Gastric adenocarcinoma of foveolar type (GA-FV) is a raspberry-shaped gastric cancer (RSGC) and garners much attention as H. pylori (Hp)-uninfected gastric cancer. However, the classification and clinicopathological and endoscopic features of RSGCs in Hp-uninfected patients are poorly defined. We designed a new histopathological classification of RSGC and compared them via endoscopic and clinicopathological characteristics. SUMMARY: From 996 patients with early gastric cancers resected by endoscopy in our hospital, we studied 24 RSGC lesions from 21 (2.4%) Hp-uninfected patients. RSGCs were classified into 3 histological types as follows: GA-FV (n = 19), gastric adenocarcinoma of fundic gland type (GA-FG, n = 2), and gastric adenocarcinoma of fundic gland mucosa type (GA-FGM, n = 3). Most of the lesions were found at the greater curvature of the upper or middle third of the stomach. GA-FV lesions were homogeneously reddish and frequently accompanied with a whitish area around the tumor and an irregular microvascular (MV) pattern; these features were confirmed histopathologically by the presence of homogeneous neoplastic foveolar epithelium with foveolar hyperplasia around the tumors. GA-FG lesions might be heterogeneously reddish with a submucosal tumor shape and regular MV pattern; these were confirmed by the presence of covered or mixed nonneoplastic epithelium on deeper regions of tumors. GA-FGM lesions might be homogeneously reddish and occasionally had a submucosal tumor shape and irregular MV pattern; these were confirmed by the presence of homogeneous neoplastic foveolar epithelium on deeper regions of the tumors. Key Messages: RSGCs in Hp-uninfected patients are classified into 3 histopathological types. For accurate diagnosis of RSGCs, it may be necessary to fully understand endoscopic features of these lesions based on these histological characteristics and to take a precise biopsy.
RESUMO
The aim of this study was to investigate appropriate analytical conditions for hydrophilic nucleosides and nucleotides (monophosphates and triphosphates) by HPLC methods using a mixed-mode AX-C18 column with anion-exchange and hydrophobic interactions by quaternary ammonium and C18, respectively, and a reversed-phase pentabromobenzyl (PBr) column with dispersion force and hydrophobic interactions by PBr group. The higher compound polarity led to stronger retention on AX-C18 (triphosphates > monophosphates > nucleosides). AX-C18 demonstrated feasible retention of nucleotides via anion-exchange interaction by increasing the salt and methanol concentrations. In contrast, on PBr, the lower compound polarity led to stronger retention. On PBr, feasible retention of both nucleosides and nucleotides was obtained via dispersion interactions with purine and pyrimidine rings by increasing the methanol concentration. Regarding the pH of phosphate buffer used as the mobile phase, pH 7.0 should be used in measuring nucleoside triphosphates on AX-C18, whereas pH 2.5 is better suited for measuring nucleotides on PBr. In terms of selectivity to highly hydrophilic nucleotides, the mixed-mode AX-C18 column had an advantage over the reverse-phase PBr column. In contrast, PBr column was more versatile than the AX-C18 column. Taken together, HPLC analyses of nucleosides and nucleotides should be carried out by optimizing the interactions between the stationary phase and nucleic acids.
Assuntos
Ácidos Nucleicos/análise , Fosfatos/análise , Cromatografia Líquida de Alta Pressão , Interações Hidrofóbicas e HidrofílicasRESUMO
Epigenetic modifiers such as decitabine (DAC), a DNA methyltransferase inhibitor, have the potential benefit of combination therapy with conventional anti-cancer drugs. This study was aimed to clarify whether DAC at the low concentration without cytotoxic effects exerts synergistic effects with conventional anti-cancer drugs in human colorectal cancer cell line, HT29â¯cells low-sensitive to DAC. DAC at very low concentration below its IC20 synergistically enhanced cytotoxicity of oxaliplatin (L-OHP), and the enhancement was the most remarkable for L-OHP among several anti-cancer drugs tested. DAC was found to be metabolized and incorporated into DNA in HT29â¯cells. Combination of L-OHP with DAC did not increase the protein expression of γH2A.X, the earliest indicator of DNA damage, in HT29â¯cells. On the other hand, although DAC alone did not produce reactive oxygen species (ROS), DAC significantly enhanced ROS production by L-OHP in HT29â¯cells. Furthermore, enhanced cytotoxicity of L-OHP by DAC was cancelled with the presence of N-acetyl-l-cysteine, a ROS scavenger. The mRNA expression of ROS-generating enzymes was significantly increased by combination in HT29â¯cells. Taken together, indirect enhancement of ROS production by DAC at the low concentration with negligible cytotoxicity should be at least involved in synergistic effects with L-OHP in HT29â¯cells with intrinsic resistance to DAC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Decitabina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Oxaliplatina/farmacologia , Apoptose , Neoplasias Colorretais/metabolismo , Sinergismo Farmacológico , Células HCT116 , Células HT29 , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used. Combination effects were analyzed by the isobologram method. SW480 cells showed the lowest sensitivity to the anticancer drugs 5-fluorouracil, SN-38 (the active form of irinotecan), and oxaliplatin. In SW480 cells, epigenetic modifiers other than VPA showed the most significant synergistic effects when used before anticancer drugs, while VPA showed synergistic effects in co- or post-treatment. In the 3 other CRC cells, synergistic effects were less frequent and weaker. The dose of anticancer drugs may be reduced by combining epigenetic modifiers in SW480 cells, which are less sensitive to anticancer drugs, unlike the more sensitive HT29, SW48, and HCT116 cell lines. These results provide useful information for understanding how to incorporate epigenetic modifiers into current CRC chemotherapy.
Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Metilases de Modificação do DNA/antagonistas & inibidores , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Inibidores Enzimáticos/uso terapêutico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Concentração Inibidora 50RESUMO
The effects of zebularine, a DNA methyltransferase inhibitor, on the invasion activity as well as intracellular expression level of let-7b, tumor suppressor microRNA, were examined in three human colorectal cancer (CRC) cell lines: SW480, SW620, and oxaliplatin-resistant SW620 (SW620/OxR). Zebularine suppressed the invasion activity of SW620 and SW620/OxR cells. The intracellular expression level of let-7b was up-regulated by zebularine in SW620 and SW620/OxR cells. The overexpression of let-7b by the transfection of let-7b mimic suppressed invasion activity in SW620 and SW620/OxR cells. These results suggest that zebularine may inhibit invasion activity by up-regulating the intracellular expression level of let-7b in high-invasive CRC cells.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Citidina/análogos & derivados , Inibidores Enzimáticos/farmacologia , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , Citidina/farmacologia , Citidina/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos , Inibidores Enzimáticos/uso terapêutico , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Humanos , Invasividade Neoplásica/prevenção & controle , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Transfecção , Regulação para CimaRESUMO
DNA hypermethylation, an epigenetic change that silences gene expression without altering nucleotide sequences, plays a critical role in the formation and progression of colorectal cancers as well as in the acquisition of drug resistance. Decitabine (DAC), a DNA methyltransferase 1 inhibitor of nucleoside analogues, has been shown to restore gene expression silenced by hypermethylation. In the present study, the mechanisms underlying both uridine and DAC uptake were examined in the human colon cancer cell line HCT116. Real-time polymerase chain reaction analysis revealed that ENT1 mRNA was the most abundant among the nucleoside transporters examined in HCT116 cells. The ENT1 protein was detected in the membrane fraction, as determined by Western blotting. The uptake of uridine or DAC was time- and concentration-dependent, but also Na(+)-independent. The uptake of these agents was inhibited by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), an inhibitor of equilibrative nucleoside transporters (ENTs), and was also decreased in cells treated with ENT1 small interfering RNA. The uptake of both uridine and DAC was inhibited by uridine, cytidine, adenosine, or inosine, while that of DAC was also inhibited by thymidine. The expression of MAGEA1 mRNA, the DNA of which was methylated in HCT116 cells, was increased by DAC treatment, and this increment was attenuated by concomitant treatment with NBMPR. The IC50 value of DAC was also increased in the presence of NBMPR. These results suggest that DAC is mainly taken up by ENT1 and that this uptake is one of the key determinants of the activity of DAC in HCT116 cells.
Assuntos
Azacitidina/análogos & derivados , Neoplasias Colorretais/metabolismo , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Antimetabólitos Antineoplásicos/metabolismo , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/metabolismo , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Proteínas de Transporte/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Metilação de DNA , Decitabina , Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Antígenos Específicos de Melanoma/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Tioinosina/análogos & derivados , Tioinosina/farmacologia , Uridina/metabolismoRESUMO
The effects of decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, on metastasis and exosomal expression of microRNAs were examined in SW620/OxR cells, a human colorectal cancer (CRC) cell line (SW620) with acquired resistance to oxaliplatin. This cell line shows an invasive phenotype by epithelial-mesenchymal transition. Two CRC cell lines, SW480, derived from primary CRC, and SW620, derived from lymph node metastasis, which were obtained from the same patient, as well as SW620/OxR, were also used in the present study. Cytarabine (Ara-C), a non-DNMT-inhibiting cytidine analog, was used as negative control of DAC. No significant difference was observed in the invasion abilities of SW480 cells treated with DAC or Ara-C. On the other hand, invasion ability was suppressed by treatment with DAC in SW620 and SW620/OxR cells. Up-regulated expression of E-cadherin, microRNA-200c (miR-200c), and miR-141 following DAC treatment indicated the acquisition of epithelial cell-like characteristics in SW620 and SW620/OxR cells. Exosomal expression levels of miR-200c and miR-141 were also up-regulated by DAC treatment in SW620 and SW620/OxR but not in SW480 cells. This increase in exosomal miRNA expression negatively correlated with invasion ability. These results suggest that DNA demethylation treatment caused acquisition of epithelial cell-like characteristics in SW620 and SW620/OxR cells. Furthermore, the observed increased exosomal expression of miR-200c and miR-141 may be an indicator or biomarker candidate for mesenchymal-epithelial transition of CRC cells.
Assuntos
Antineoplásicos/farmacologia , Azacitidina/análogos & derivados , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Azacitidina/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Metilação de DNA , Metilases de Modificação do DNA/antagonistas & inibidores , Decitabina , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Exossomos/metabolismo , Humanos , Invasividade Neoplásica/genética , Compostos Organoplatínicos/farmacologia , OxaliplatinaRESUMO
Epithelial-mesenchymal transition (EMT) and changes in the expression of the microRNA-200 (miR-200) family were examined in the human colorectal cancer (CRC) cell line SW620 with acquired oxaliplatin (L-OHP) resistance. Two CRC cell lines, SW480, derived from primary CRC, and SW620, derived from lymph node metastasis, which were obtained from the same patient, were used in the present study. L-OHP-resistant SW620 cells were obtained by exposure to L-OHP for 155 d. The concentration of L-OHP was increased to 80 µM in a stepwise manner. The IC50 value of L-OHP was increased 16-fold in L-OHP-resistant SW620 cells, which also displayed mesenchymal cell-like characteristics, such as the down-regulation of E-cadherin and up-regulation of vimentin. However, L-OHP-resistant SW480 cells were not obtained when the concentration of L-OHP was increased in a similar stepwise manner. The expression levels of members of the miR-200 family (miR-200a, miR-200b, miR-429, miR-200c, and miR-141) were significantly higher in SW480 cells than in SW620 cells. The expression levels of miR-200c and miR-141 were significantly lower in L-OHP-resistant SW620 cells than in control SW620 cells. L-OHP-resistant SW620 cells did not exhibit cross-resistance to other anti-cancer drugs used to treat CRC, such as 5-fluorouracil, irinotecan, and the active metabolite of irinotecan (SN-38). These results suggest that the down-regulated expression of miR-200c and miR-141 plays a role in selective resistance to L-OHP and EMT in CRC cells during repeated treatments with L-OHP.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Compostos Organoplatínicos/farmacologia , Antineoplásicos/uso terapêutico , Caderinas/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Regulação para Baixo , Humanos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Vimentina/metabolismoRESUMO
We investigated the effects of epigenetic modifiers such as DNA methyltransferase (DNMT) or histone deacetylase (HDAC) inhibitors on the cytotoxicity induced by 3 anticancer drugs (5-fluorouracil (5-FU), irinotecan (CPT-11) or its active form SN38, and oxaliplatin (L-OHP)) in human colorectal cancer (CRC) cells. Cytotoxicity in 4 CRC cell lines (HT29, SW480, SW48 and HCT116) was examined by colorimetric assay after drug treatment for 72 h. The effects of drug combinations were analyzed by an isobologram method. SW480 cells showed the lowest sensitivity to cytotoxicity induced by the anticancer drugs among the 4 CRC cell lines. In SW480 cells, DNMT inhibitors, such as decitabine (DAC), azacytidine and zebularine (Zeb), showed synergic effects on the cytotoxicity induced by anticancer drugs except for SN-38 plus Zeb, while HDAC inhibitors, trichostatin A, suberoylanilide hydroxamic acid and valproic acid, showed antagonistic effects. DAC showed the most potent synergic effects among the epigenetic modifiers studied. Thus, we examined whether the synergic effect of DAC is observed in other different CRC cell lines, HT29, SW48 and HCT116 cells. In all 4 CRC cell lines, the cytotoxicity of L-OHP was enhanced in a synergic manner by co-treatment with DAC. However, synergic effects of DAC with 5-FU or CPT-11 (SN-38) were not observed in 4 CRC cell lines.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Azacitidina/análogos & derivados , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Epigênese Genética , Fluoruracila/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Neoplasias do Colo/genética , DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Decitabina , Sinergismo Farmacológico , Células HCT116 , Células HT29 , Inibidores de Histona Desacetilases/farmacologia , Humanos , Irinotecano , OxaliplatinaRESUMO
Linked color imaging (LCI) for image-enhanced endoscopy (IEE) highlights mucosal color differences. We investigated risk factors associated with mucosal redness of the duodenal bulb using LCI. Consecutive patients were retrospectively selected after their duodenal bulbs were observed via LCI. A symptom questionnaire (Izumo scale) was completed. The LCI of the duodenal bulb was subjectively evaluated on whether redness was present and objectively evaluated based on L* a* b* color values. The clinical characteristics of the 302 study participants were: male/female, 120/182; mean age, 70.9 years. Twenty-one cases (7.0%) were in the redness (+) group. After multiple regression analysis, independent predictors for the red component (a*) of the duodenal bulb using LCI were: age (ß = -0.154, p < 0.01), female (ß = -0.129, p < 0.05), body mass index (BMI; ß = -0.136, p < 0.05), Helicobacter pylori eradication (ß = 0.137, p < 0.05), endoscopic gastric mucosal atrophy score (EGAS; ß = -0.149, p < 0.05), and constipation-related quality of life (QOL) (ß = -0.122, p < 0.05) scores. Lower age, lower BMI, lower EGAS, a constipation-related QOL score, post-H. pylori eradication, and being male were associated with mucosal redness in the duodenal bulb with IEE using LCI.
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Introduction: In recent years, the frequency of idiopathic peptic ulcers (IPUs) has increased. However, the clinicopathological characteristics of IPU have not been fully elucidated and treatment methods for recurrent and refractory cases have not yet been established. Case Presentation: A man in his forties complained of epigastric discomfort. Esophagogastroduodenoscopy revealed a gastric ulcer in the lesser curvature of the gastric angle. After Helicobacter pylori was eradicated, the gastric ulcer recurred despite the administration of a potassium competitive acid blocker (PCAB), and a diagnosis of IPU was made. Twenty-four-hour intragastric pH monitoring revealed insufficient gastric acid suppression. Misoprostol was added to the patient's treatment. Subsequently, the ulcer healed and recurrence was not observed. Conclusion: For refractory IPU, the evaluation of pathophysiological function through 24-h gastric pH monitoring may lead to the selection of an appropriate treatment. If a proton pump inhibitor and PCAB do not improve the IPU, combination treatment with misoprostol may be considered as an option.
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An 86-year-old man presented with anemia. He underwent abdominal contrast-enhanced computed tomography, gastroscopy, and colonoscopy without any bleeding detected. Small bowel capsule endoscopy (SBCE) revealed a reddish polypoid lesion with blood oozing into the jejunum. Antegrade double-balloon endoscopy (DBE) revealed a 5 mm sized protrusion into the jejunum. Endoscopic mucosal resection (EMR) was difficult; the lesion was snared and resected before energization. Clips prevented further bleeding and the lesion's position was marked with a tattoo. Histopathological examination of the lesion led to a diagnosis of capillary hemangioma. After 11 months, the patient was again anemic. A reddish polypoid lesion oozing blood near the tattoo was found by SBCE. Another antegrade DBE showed a 7 mm sized protrusion near the tattoo. The lesion was successfully treated by EMR. Histopathological examination revealed the residual recurrence of a small intestinal capillary hemangioma. The patient recovered from anemia after the EMR. Two months later, SBCE showed no findings around the tattoo. Hemangiomas account for 7-10% of benign small intestinal tumors; most are cavernous hemangiomas, and capillary hemangiomas are rare. We report a rare case of a recurring small intestinal capillary hemangioma detected by SBCE and treated using DBE. We also review the literature.
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Background: Barrett's esophagus and esophageal adenocarcinoma cases are increasing as gastroesophageal reflux disease increases. Using artificial intelligence (AI) and linked color imaging (LCI), our aim was to establish a method of diagnosis for short-segment Barrett's esophagus (SSBE). Methods: We retrospectively selected 624 consecutive patients in total at our hospital, treated between May 2017 and March 2020, who experienced an esophagogastroduodenoscopy with white light imaging (WLI) and LCI. Images were randomly chosen as data for learning from WLI: 542 (SSBE+/- 348/194) of 696 (SSBE+/- 444/252); and LCI: 643 (SSBE+/- 446/197) of 805 (SSBE+/- 543/262). Using a Vision Transformer (Vit-B/16-384) to diagnose SSBE, we established two AI systems for WLI and LCI. Finally, 126 WLI (SSBE+/- 77/49) and 137 LCI (SSBE+/- 81/56) images were used for verification purposes. The accuracy of six endoscopists in making diagnoses was compared to that of AI. Results: Study participants were 68.2 ± 12.3 years, M/F 330/294, SSBE+/- 409/215. The accuracy/sensitivity/specificity (%) of AI were 84.1/89.6/75.5 for WLI and 90.5/90.1/91.1/for LCI, and those of experts and trainees were 88.6/88.7/88.4, 85.7/87.0/83.7 for WLI and 93.4/92.6/94.6, 84.7/88.1/79.8 for LCI, respectively. Conclusions: Using AI to diagnose SSBE was similar in accuracy to using a specialist. Our finding may aid the diagnosis of SSBE in the clinic.
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We herein report a rare case of Yersinia enterocolitica enteritis with a fever and abdominal pain followed by erythema nodosum (EN) a few days later. The diagnosis was confirmed based on characteristic colonoscopy and computed tomography findings, pathology, and mucosal culture. Yersinia enteritis is a curable disease provided a proper diagnosis and treatment are performed. Although EN is a rare clinical course, it should still be considered as a differential diagnosis.
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Enterite , Eritema Nodoso , Yersiniose , Yersinia enterocolitica , Humanos , Yersiniose/complicações , Yersiniose/diagnóstico , Eritema Nodoso/complicações , Eritema Nodoso/diagnóstico , Enterite/complicações , Enterite/diagnóstico , Diagnóstico DiferencialRESUMO
A mediastinal thoracic duct cyst that originates from the thoracic duct is a very rare disease in the mediastinum. There have been no reports of mediastinal thoracic duct cyst infection caused by endoscopic treatment. This is the first case of mediastinal thoracic duct cyst infection after endoscopic submucosal dissection for early esophageal cancer. We herein report a 75-year-old man with mediastinal thoracic duct cyst infection caused by esophageal endoscopic submucosal dissection. In cases where a mediastinal thoracic duct cyst is found before performing endoscopic esophageal treatment, we should carefully consider the potential risk of post-treatment cyst infection.