Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-32003276

RESUMO

Background: Endoscopic submucosal tunnel dissection (ESTD) has recently been an effective procedure for resecting large early esophageal neoplasm. However, excessive dissection beyond the distal limit may occur because the prepared distal end often cannot be distinguished through the tunnel. This study aimed to assess the efficacy and safety of a novel crystal violet navigation (CVN) for identifying the distal end.Material and methods: In the observational case series study, all 22 patients who underwent esophageal ESTD using the CVN were included. When setting the distal end, the distal incision line was dyed purple using a crystal violet solution. The rates of purple color identified via the tunnel, successful tunnel penetration without extra dissection, en bloc and curative resection, procedure time for ESTD and CVN, and procedure-associated complications were evaluated.Results: The rates of purple color and successful tunnel penetration were both 100%. En bloc and curative resection were 100%, and 86%, respectively. The mean total procedure time was 103.9 ± 46.2 (mean ± SD) minutes, while the mean time for the CVN was 14.1 ± 3.44 s. No complications were observed.Conclusions: The simple CVN method can be a navigation tool for identifying the distal end during the ESTD procedure.

2.
Anticancer Res ; 40(1): 121-132, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892560

RESUMO

BACKGROUND/AIM: Pancreatic neuroendocrine tumors (pNETs) are rare pancreatic neoplasms, and therapeutic options for pNETs are limited. Metformin is an anti-hypoglycemic drug that appears to have anticancer effects. However, little is known about the effect of metformin on pNETs. In this study, we investigated the anti-proliferative effect of metformin on a human pNET cell line. MATERIALS AND METHODS: The anti-proliferative properties of metformin were evaluated in QGP-1 and NCI-H727 cells using a cell counting kit-8 assay. Xenograft mouse models were used to assess the tumor effect in vivo. RESULTS: Metformin inhibited the proliferation and anti-tumor growth of QGP-1 cells, accompanied by their arrest during the cell cycle at the G0/G1 phase. Immunohistochemical analysis of tumor tissues revealed down-regulation of cyclin D1 and proliferating cell nuclear antigen in the metformin-treated group. Additionally, metformin induced apoptosis, and the expression of survivin and claspin were decreased in metformin-treated QGP-1 cells according to the apoptosis array. Furthermore, the angiogenic related protein TIMP-1 was down-regulated, and its miRNA expression was altered by metformin in QGP-1 cells. CONCLUSION: Taken together, our study demonstrated the therapeutic potential of metformin and provides molecular mechanistic insights into its anti-tumoral effect on pNETs. This study is the first one describing anti-tumoral effects in pNETs.


Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Metformina/farmacologia , Biomarcadores , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , MicroRNAs/genética , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Artigo em Inglês | MEDLINE | ID: mdl-31905024

RESUMO

Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared to nontumor tissue. We thus examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancer-related deaths. HCC tissue samples from 29 patients who underwent hepatectomy at our hospital in 2002-2013 were obtained. We extracted the total RNA and analyzed it by microRNA array, real-time RT-PCR, and three comparisons: (1) HBV-related HCC and adjacent nontumor tissue, (2) HCV-related HCC and adjacent nontumor tissue, and (3) non-HBV-, non-HCV-related HCC and adjacent nontumor tissue. We also performed a functional analysis of miRNAs specific for HBV-related HCC by using HBV-positive HCC cell lines. MiR-210-3p expression was significantly increased only in the HBV-related HCC tissue samples. MiR-210-3p expression was upregulated, and the levels of its target genes were reduced in the HBV-positive HCC cells. The inhibition of miR-210-3p enhanced its target gene expression in the HBV-positive HCC cells. In addition, miR-210-3p regulated the HBx expression in HBV-infected Huh7/NTCP cells. The enhanced expression of miR-210-3p was detected specifically in HBV-related HCC and regulated various target genes including HBx in the HBV-positive HCC cells. MiR-210-3p might thus be a new biomarker for the risk of HBV-related HCC.

4.
J Gastrointestin Liver Dis ; 28(4): 397-404, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31826062

RESUMO

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) has become a standard treatment for early gastric neoplasia. However, as the upper and middle body of the greater curvature has a rich vasculature and submucosal fibrosis, ESD of neoplasia in these locations requires a specific strategy. We aimed to investigate the efficacy and safety of the J-shaped superficial cutting and splashed submucosal dissection (JSCS) technique for neoplasia of the greater curvature by comparing ESD using JSCS with conventional ESD. METHODS: Twenty-two patients who underwent ESD for gastric neoplasia affecting the upper and middle body of the greater curvature were divided into two groups for retrospective analysis. Nine patients underwent conventional ESD (c-Group), while 13 underwent ESD with JSCS (j-Group). Primary outcome was the en bloc resection rate. Secondary outcomes included complete resection (R0) rate, procedure time, perforation rate, total bleeding time, and the total number of massive bleeding events and of hemostatic forceps times applied during ESD. RESULTS: There were no significant differences between both groups (c-Group vs j-Group) in en bloc resection rate, or R0 resection rate. Compared with the c-Group, the j-Group tended to have a decreased mean procedure time (mean 133 minutes vs 74 minutes, p=0.11) and perforation rate (11% vs 0%, p=0.41). Compared with the c-Group, the j-Group had significantly fewer bleeding incidents (13.4 times vs 6.6 times, p=0.0095), shorter total bleeding time (17.6 min vs 7.4 min, p=0.036), and fewer usages of hemostatic forceps (6.3 times vs 2.4 times, p=0.026) during ESD. CONCLUSION: Endoscopic submucosal dissection with JSCS is superior to conventional ESD, as it reduces intraprocedural bleeding. This technique has the potential to become the standard strategy for neoplasia affecting the upper and middle body of the greater curvature.

5.
Anticancer Drugs ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31815765

RESUMO

Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-ß, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma.

6.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261874

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Fase S/efeitos dos fármacos , Telmisartan/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Linhagem Celular Tumoral , Ciclina A2/genética , Ciclina A2/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , Telmisartan/uso terapêutico , Trombospondina 1/genética , Trombospondina 1/metabolismo
7.
Int J Mol Sci ; 20(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146370

RESUMO

Galectin-9 (Gal-9) enhances tumor immunity mediated by T cells, macrophages, and dendritic cells. Its expression level in various cancers correlates with prognosis. Furthermore, Gal-9 directly induces apoptosis in various cancers; however, its mechanism of action and bioactivity has not been clarified. We evaluated Gal-9 antitumor effect against esophageal squamous cell carcinoma (ESCC) to analyze the dynamics of apoptosis-related molecules, elucidate its mechanism of action, and identify relevant changes in miRNA expressions. KYSE-150 and KYSE-180 cells were treated with Gal-9 and their proliferation was evaluated. Gal-9 inhibited cell proliferation in a concentration-dependent manner. The xenograft mouse model established with KYSE-150 cells was administered with Gal-9 and significant suppression in the tumor growth observed. Gal-9 treatment of KYSE-150 cells increased the number of Annexin V-positive cells, activation of caspase-3, and collapse of mitochondrial potential, indicating apoptosis induction. c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) phosphorylation were activated and could be involved in apoptosis. Therefore, Gal-9 induces mitochondria-mediated apoptosis of ESCC and inhibits cell proliferation in vitro and in vivo with JNK and p38 activation.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Galectinas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias Esofágicas/tratamento farmacológico , Galectinas/uso terapêutico , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo
9.
J Gastroenterol Hepatol ; 34(1): 22-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30069935

RESUMO

Rescue therapy for gastrointestinal (GI) refractory bleeding, perforation, and fistula has traditionally required surgical interventions owing to the limited performance of conventional endoscopic instruments and techniques. An innovative clipping system, the over-the-scope clip (OTSC), may play an important role in rescue therapy. This innovative device is proposed as the final option in endoscopic treatment. The device presents several advantages including having a powerful sewing force for closure of GI defects using a simple mechanism and also having an innovative feature, whereby a large defect and fistula can be sealed using accessory forceps. Consequently, it is able to provide outstanding clinical effects for rescue therapy. This review clarifies the current status and limitations of OTSC according to different indications of GI refractory disease, including refractory bleeding, perforation, fistula, and anastomotic dehiscence. An extensive literature search identified studies reported 10 or more cases in which the OTSC system was applied. A total of 1517 cases described in 30 articles between 2010 and 2018 were retrieved. The clinical success rates and complications were calculated overall and for each indication. The average clinical success rate was 78% (n = 1517) overall, 85% for bleeding (n = 559), 85% (n = 351) for perforation, 52% (n = 388) for fistula, 66% (n = 97) for anastomotic dehiscence, and 95% (n = 122) for other conditions, respectively. The overall and severe OTSC-associated complications were 1.7% (n = 23) and 0.59% (n = 9), respectively. This review concludes that the OTSC system may serve as a safe and productive device for GI refractory diseases, albeit with limited success for fistula.


Assuntos
Fístula do Sistema Digestório/terapia , Endoscopia Gastrointestinal/instrumentação , Hemorragia Gastrointestinal/terapia , Perfuração Intestinal/terapia , Fístula Anastomótica/terapia , Endoscopia Gastrointestinal/efeitos adversos , Perfuração Esofágica/terapia , Humanos , Terapia de Salvação
10.
J Med Case Rep ; 12(1): 227, 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30139375

RESUMO

BACKGROUND: Neuroendocrine cell carcinoma is a rare variant of esophageal carcinoma. The characteristic clinical features and diagnosis of superficial neuroendocrine cell carcinoma remain to be established. We report a rare case of superficial coexistence of neuroendocrine cell carcinoma with squamous cell carcinoma treated by endoscopic submucosal dissection, and regional lymph node metastasis was detected after additional surgical treatment. CASE PRESENTATION: A 77-year-old Japanese man with esophageal squamous cell carcinoma received endoscopic submucosal dissection in en-bloc resection. Histopathological findings showed that lymphovascular invasion by the neuroendocrine cell carcinoma component occurred in the deep part of the muscularis mucosa. Regional lymph node metastasis was identified after additional surgical treatment. After surgical treatment, our patient received chemotherapy consisting of etoposide and carboplatin for 3 months. He is alive and shows no sign of disease recurrence 12 months after surgery. CONCLUSIONS: This case report highlights the fact that even if neuroendocrine cell carcinoma is small and limited to superficial, the tumor has the potential for metastasis if lymphovascular invasion by the neuroendocrine cell carcinoma component occurs. In addition, this case indicates the necessity of close follow-up of small neuroendocrine cell carcinoma after treatment.


Assuntos
Carcinoma Neuroendócrino/patologia , Carcinoma de Células Escamosas/patologia , Mucosa Esofágica/cirurgia , Neoplasias Esofágicas/patologia , Linfonodos/patologia , Idoso , Carcinoma Neuroendócrino/cirurgia , Carcinoma de Células Escamosas/cirurgia , Dissecação , Mucosa Esofágica/patologia , Neoplasias Esofágicas/cirurgia , Esofagoscopia , Humanos , Japão , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Masculino
11.
Oncol Lett ; 15(1): 407-414, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29387226

RESUMO

Pancreatic cancer is the eighth-leading cause of cancer-associated mortality in males and the ninth-leading cause in females worldwide. Even when diagnosed early enough to be potentially resectable, the prognosis of invasive pancreatic cancer is poor. Galectin-9 (Gal-9) is a tandem-repeat type galectin that has recently been demonstrated to possess an anti-proliferative effect on cancer cells. Therefore, the present study evaluated the effects of Gal-9 on the proliferation of human pancreatic cancer cells and examined the microRNAs that are associated with the antitumor effects of Gal-9. Gal-9 suppressed the proliferation of multiple pancreatic cancer cell lines. In addition, Gal-9 treatment increased the levels of caspase-cleaved keratin 18 and the expression of cytochrome c in pancreatic cancer cell lines. This data suggests that Gal-9 induces intrinsic apoptosis in pancreatic cancer cell lines through the caspase-dependent and caspase-independent pathways. In addition, Gal-9 reduced the expression levels of phosphorylated epidermal growth factor receptor and numerous receptor tyrosine kinases (RTKs). In conclusion, Gal-9 may suppress the growth of human pancreatic cancer cells in vitro. These findings suggest that Gal-9 may be a new therapeutic agent for the treatment of pancreatic cancer.

12.
Oncol Lett ; 15(1): 528-532, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29391887

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Although the clinical success rate for the treatment of early-stage HCC has improved, the prognosis of advanced HCC remains poor owing to the high recurrence rate and the refractory nature of HCC for various anticancer drugs. A better understanding of the pathogenesis of HCC is therefore critically needed in order to treat HCC, including its genetic alterations. Next-generation sequencing (NGS) has provided an unbiased platform to systematically identify gene mutations and reveal the pathogenesis of various cancers. In the present study, a total of 118 samples (59 liver tissues including cancer and adjacent normal tissues) were sequenced using the AmpliSeq Hotspot Cancer Panel (version 2). The most common somatic mutations identified were tumor protein 53 (TP53; 35.6%) and ß-catenin 1 (CTNNB1; 30.5%), and the most frequent variants of those genes were missense variants. In addition, somatic mutations including those in genes encoding colony-stimulating factor 1 receptor (5.1%), epidermal growth factor receptor (6.8%), RET proto-oncogene (3.4%), Erb-B2 receptor tyrosine kinase 4 (ERBB4; 1.7%) and serine/threonine kinase 11 (STK11, also known as liver kinase B1; 6.8%) were also identified at a low frequency in patients with HCC. A frameshift variant in STK11, a splice acceptor variant in TP53, a splice region variant in ERBB4 and a stop-gained variant in TP53 were also specifically determined. The most abundant alteration was a C:G>T:A transition (50%) and other transversions, i.e., C:G>G:C (19.6%), T:A>C:G (19.6%), C:G>A:T (12.5%), T:A>G:C (12.5%) and T:A>A:T (5.4%). This spectrum pattern differs from that in other solid tumors. TP53 mutations in the tumors at advanced stages were significantly more frequent compared with those in early-stage tumors. Additionally, age (<70 vs. ≥70 years) was significantly associated with CTNNB1 mutations. Using NGS, a number of novel gene mutations were identified in HCC, including established mutations and disproved mutations. The results of the present study offer new insight and improved understanding of the etiology and the development of HCC.

13.
Int J Clin Oncol ; 23(4): 707-714, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29446041

RESUMO

BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3. METHODS: A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens. RESULTS: The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Endoscopia/métodos , Imagem de Banda Estreita/métodos , Neoplasias do Colo do Útero/patologia , Adulto , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasia Intraepitelial Cervical/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem
14.
Oncol Rep ; 38(5): 2825-2835, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29048654

RESUMO

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer-related death. Telmisartan, a widely used antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB) that might inhibit cancer cell proliferation, but the mechanisms through which telmisartan affects various cancers remain unknown. The aim of the present study was to evaluate the effects of telmisartan on human HCC and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines. In our experiments, telmisartan inhibited the proliferation of HLF, HLE and HepG2 cells, which represent poorly differentiated types of HCC cells. However, HuH-7 and PLC/PRF/5 cells, which represent well-differentiated types of HCC cells, were not sensitive to telmisartan. Telmisartan induced G0/G1 cell cycle arrest of HLF cells by inhibiting the G0-to-G1 cell cycle transition. This blockade was accompanied by a marked decrease in the levels of cyclin D1, cyclin E and other cell cycle-related proteins. Notably, the activity of the AMP-activated protein kinase (AMPK) pathway was increased, and the mammalian target of rapamycin (mTOR) pathway was inhibited by telmisartan treatment. Additionally, telmisartan increased the level of caspase-cleaved cytokeratin 18 (cCK18), partially contributed to the induction of apoptosis in HLF cells and reduced the phosphorylation of ErbB3 in HLF cells. Furthermore, miRNA expression was markedly altered by telmisartan in vitro. In conclusion, telmisartan inhibits human HCC cell proliferation by inducing cell cycle arrest.


Assuntos
Benzimidazóis/farmacologia , Benzoatos/farmacologia , Carcinoma Hepatocelular/genética , Proliferação de Células/efeitos dos fármacos , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/tratamento farmacológico , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , MicroRNAs/genética , Telmisartan
15.
Int J Oncol ; 51(6): 1674-1684, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29075786

RESUMO

Cholangiocarcinoma (CCA) is at an advanced stage at the time of its diagnosis, and developing a more effective treatment of CCA would be desirable. Angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan may inhibit cancer cell proliferation, but the mechanisms by which telmisartan affects various cancers remain unknown. In this study, we evaluated the effects of telmisartan on human CCA cells and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on CCA cells using two cell lines, HuCCT-1 and TFK-1. In our experiments, telmisartan inhibited the proliferation of HuCCT-1 and TFK-1 cells. Additionally, telmisartan induced G0/G1 cell cycle arrest via blockade of the G0 to G1 cell cycle transition. Notably, telmisartan did not induce apoptosis in HuCCT-1 cells. This blockade was accompanied by a strong decrease in cell cycle-related protein, especially G1 cyclin, cyclin D1, and its catalytic subumits, Cdk4 and Cdk6. Telmisartan reduced the phosphorylation of EGFR (p-EGFR) and TIMP-1 by using p-RTK and angiogenesis array. Furthermore, miRNA expression was markedly altered by telmisartan in HuCCT-1. Telmisartan inhibits tumor growth in CCA xenograft model in vivo. In conclusion, telmisartan was shown to inhibit human CCA cell proliferation by inducing cell cycle arrest.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Benzimidazóis/farmacologia , Benzoatos/farmacologia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Neoplasias dos Ductos Biliares/irrigação sanguínea , Neoplasias dos Ductos Biliares/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colangiocarcinoma/irrigação sanguínea , Colangiocarcinoma/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/biossíntese , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Distribuição Aleatória , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Telmisartan , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Gut Liver ; 11(5): 735-737, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28874041

RESUMO

Endoscopic treatment can be a curative option for small carcinoid tumors with an extremely low risk of metastasis. Since most carcinoid tumors are characterized by a specific growth pattern in the submucosal (SM) layer, specialized endoscopic techniques for deeper resection to achieve clear vertical margins are needed. The endoscopic submucosal dissection (ESD) method in the SM space is superior to conventional endoscopic mucosal resection. However, the standard ESD technique sometimes fails to provide complete deep SM dissection due to insufficient SM lifting. Here, to resolve this problem, we describe our initial experience with an endoscopic SM tunneling technique that is effective for treating rectal carcinoid tumors.


Assuntos
Tumor Carcinoide/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Intestinais/cirurgia , Neoplasias Retais/cirurgia , Feminino , Humanos , Mucosa Intestinal/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Endosc Int Open ; 5(8): E695-E705, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28782002

RESUMO

BACKGROUND AND STUDY AIMS : Endoscopic ultrasound-guided fine needle aspiration (FNA) for gastrointestinal subepithelial lesions (SELs) has limited diagnostic accuracy due to technical problems and small lesion size. We previously reported a novel submucosal tunneling biopsy (STB) technique for sampling SELs. This study aimed to evaluate the diagnostic ability and safety of STB compared to that of FNA for SELs. PATIENTS AND METHODS : The study was a non-randomized, prospective comparative study with crossover design in patients with endoluminal gastric SELs. Forty-three patients, including 29 cases with lesions < 2 cm were enrolled. A crossover design with 2 intervention stages (Group A: FNA followed by STB for 23 SELs, Group B: STB followed by FNA for 20 SELs) was implemented. The primary outcome was the diagnostic yield (DY). Secondary outcomes were technical success rate, procedure time, complication rate, and sample quality. RESULTS : The DY of STB was significantly higher than that of FNA (100 % vs. 34.8 %; P  < 0.0001) in group A, including 100 % in overall STB. The technical success rate of STB was significantly higher than that of FNA (100 % vs. 56.5 %; P  = 0.0006), whereas the median procedure time of STB was significantly longer than that of FNA (37 minutes vs. 18 minutes; P  < 0.0001). The median specimen area of STB samples was markedly larger than that of FNA samples (5.54 mm 2 vs. 0.69 mm 2 ; P  < 0.001). No complications occurred in either method. CONCLUSIONS: STB had significantly superior diagnostic ability and a more adequate sample quality than FNA for endoluminal gastric SELs, indicating the suitability of STB for small SELs. CLINICAL TRIAL REGISTRATION: UMIN 000006754.

19.
Oncol Lett ; 14(1): 355-362, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693176

RESUMO

Narrow band imaging with magnifying endoscopy (NBI-ME), which is useful for the assessment of micro-vessels, has excellent diagnostic potential for early gastrointestinal epithelial neoplasia. Conventional diagnostic tools for uterine cervical epithelial tumors are still unsatisfactory. An accurate diagnostic tool for uterine cervical epithelial tumors is required to preserve the reproductive ability of young women with uterine cervical tumors. Flexible NBI-ME was performed in patients with cervical squamous cell lesions that required further examinations based on their Pap smear results (cytology ≥ low-grade squamous intraepithelial lesion) at Kagawa University Hospital between April 2014 and April 2015. NBI-ME results concordant with the punch biopsy sites were compared with the histological results. A retrospective review of the NBI-ME images identified abnormal NBI-ME results regarding micro-vascular patterns. All images were categorized as having abnormal features. NBI-ME revealed the following vascular pattern differences of different stage tumors: Dot-like vessels without irregular arrangements and high density in cervical intraepithelial neoplasia (CIN) CIN1-CIN2; dot-like vessels with irregular arrangements and high density in CIN3-carcinoma in situ; crawling vessels in minimum invasive cancer; and willow branch vessels and new tumor vessels in invasive cancer. NBI-ME may be an effective diagnostic tool for uterine cervical epithelial tumors, which may lead to the establishment of a novel classification system.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA