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1.
Helicobacter ; 26(2): e12786, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33596339

RESUMO

BACKGROUND: Pathogens capable of impacting gastrointestinal tract tumor development are located in the oral cavity, but whether these oral bacteria are able to colonize the gastric mucosa in gastric cancer (GC) patients and whether Helicobacter pylori infection can influence this process remains to be established. METHODS: Microbial 16S rDNA deep sequencing was conducted to characterize bacteria present in paired gastric mucosa and tongue coating samples in 27 patients with superficial gastritis (SG) and 11 GC patients. RESULTS: While the overall composition of the gastric mucosa and tongue coating microbiomes differed substantially, certain bacteria were present in both of these communities. The co-occurrence of bacteria between the tongue coating and gastric mucosa differed significantly between SG and GC patients. Of the 15 most abundant shared oral bacteria genera (the core shared oral bacteria), which were associated with differences in microbiota composition between these tongue coating and gastric mucosa, three were enriched in the gastric mucosa of GC patients relative to SG patients, whereas, 12 were depleted in GC patient samples. Furthermore, the prevalence and relative abundance of these core shared oral bacteria in the gastric mucosa were also linked to H. pylori infection status, and the core shared oral bacteria were also associated with the overall composition of the gastric mucosal microbiome. CONCLUSIONS: Helicobacter pylori infections are linked to the co-occurrence of bacteria in the oral microbiome and the gastric mucosal microbiome. Ectopic colonization of oral microbes may be a primary driver of H. pylori-induced gastric microbial dysbiosis in patients with GC.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Mucosa Gástrica , Helicobacter pylori/genética , Humanos , Boca , RNA Ribossômico 16S
2.
Dig Dis Sci ; 66(5): 1673-1682, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32591968

RESUMO

BACKGROUND: How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC. METHODS: Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses. RESULTS: GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community. CONCLUSIONS: GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.


Assuntos
Bactérias/isolamento & purificação , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Microbioma Gastrointestinal , Lesões Pré-Cancerosas/microbiologia , Neoplasias Gástricas/microbiologia , Idoso , Bactérias/genética , Biópsia , Disbiose , Feminino , Gastrectomia , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastrite/patologia , Gastrite/cirurgia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Ribotipagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
3.
World J Gastroenterol ; 26(43): 6867-6879, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33268967

RESUMO

BACKGROUND: Hypoxemia due to respiratory depression and airway obstruction during upper gastrointestinal endoscopy with sedation is a common concern. The Wei nasal jet tube (WNJT) is a new nasopharyngeal airway with the ability to provide supraglottic jet ventilation and oxygen insufflation via its built-in wall channel. The available evidence indicates that with a low oxygen flow, compared with nasal cannula, the WNJT does not decrease the occurrence of hypoxemia during upper gastrointestinal endoscopy with propofol sedation. To date, there has been no study assessing the performance of WNJT for supplemental oxygen during upper gastrointestinal endoscopy with sedation when a moderate oxygen flow is used. AIM: To determine whether the WNJT performs better than the nasal prongs for the prevention of hypoxemia during gastroscopy with propofol mono-sedation when a moderate oxygen flow is provided in patients with a normal body mass index. METHODS: This study was performed in 291 patients undergoing elective gastroscopy with propofol mono-sedation. Patients were randomized into one of two groups to receive either the WNJT (WNJT group, n = 147) or the nasal cannula (nasal cannula group, n = 144) for supplemental oxygen at a 5-L/min flow during gastroscopy. The lowest SpO2 during gastroscopy was recorded. The primary endpoint was the incidence of hypoxemia or severe hypoxemia during gastroscopy. RESULTS: The total incidence of hypoxemia and severe hypoxemia during gastroscopy was significantly decreased in the WNJT group compared with the nasal cannula group (P = 0.000). The lowest median SpO2 during gastroscopy was significantly higher (98%; interquartile range, 97-99) in the WNJT group than in the nasal cannula group (96%; interquartile range, 93-98). Epistaxis by device insertion in the WNJT group occurred in 7 patients but stopped naturally without any treatment. The two groups were comparable in terms of the satisfaction of physicians, anesthetists and patients. CONCLUSION: With a moderate oxygen flow, the WNJT is more effective for the prevention of hypoxemia during gastroscopy with propofol mono-sedation compared with nasal prongs, but causing slight epistaxis in a few patients.


Assuntos
Propofol , Índice de Massa Corporal , Cânula , Gastroscopia , Humanos , Hipóxia/etiologia , Oxigênio , Propofol/efeitos adversos
8.
Trials ; 19(1): 602, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30382904

RESUMO

BACKGROUND: Hypoxemia is a major complication in obese patients undergoing gastrointestinal endoscopy under intravenous anesthesia or sedation due to altered airway anatomy. We design this randomized controlled trial (RCT) to compare efficacy and safety of the Wei nasal jet tube (WNJT) and nasal prongs for supplement oxygen during gastroscopy with intravenous propofol anesthesia in obese patients. METHODS: The study will be a single-center, prospective RCT. A total of 308 obese patients will be recruited and randomly assigned to receive either the WNJT (group A) or nasal prongs (group B). During gastroscopy with intravenous propofol anesthesia, 5 L/min of oxygen will be delivered through the jet port of the WNJT in the group A and via the nasal prongs in the group B. The primary outcome is the incidence of hypoxemia and severe hypoxemia. The secondary outcomes are adverse events during the gastroscopy, postoperative complications, and satisfaction of the anesthetist, physician, and patient. DISCUSSION: This RCT aims to clarify whether the WNJT can result in reduced incidences of hypoxemia and complications and provide improved satisfaction to the anesthetist, physician, and patient. Thus, it can be determined if the WNJT is a useful tool for supplement oxygen in obese patients undergoing gastroscopy with intravenous propofol anesthesia. The results will provide the evidence for anesthesiologists to make a decision regarding the choice of supplementary oxygen methods in this condition. TRIAL REGISTRATION: Chinese Clinical Trial, ChiCTR-IOR-17013089 . Registered on 23 October 2017.


Assuntos
Anestesia Intravenosa , Gastroscopia/métodos , Hipóxia/prevenção & controle , Obesidade/cirurgia , Oxigênio/administração & dosagem , Propofol/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos
9.
Dig Endosc ; 30(1): 57-64, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28816373

RESUMO

BACKGROUND AND AIM: To investigate the efficacy and safety of premedication with simethicone/Pronase during esophagogastroduodenoscopy (EGD) with sedation. METHODS: Six hundred and ten patients were randomly allocated to two groups based on type of premedication given. Premedication used in the control group was 10 mL lidocaine hydrochloride mucilage (LHM, N = 314) and premedication used in the intervention group was 80 mL simethicone/Pronase solution plus 10 mL lidocaine hydrochloride mucilage (SP/LHM, N = 296). EGD was done under sedation. Visibility scores, number of mucosal areas that needed cleansing, water consumption for cleansing, time taken for examination, diminutive lesions, pathological diagnosis, patients' gag reflex and oxygenation (pulse oximetry) were recorded. RESULTS: SP/LHM has significantly lower total visibility score than LHM (7.978 ± 1.526 vs 6.348 ± 1.097, P < 0.01). During the procedure, number of intragastric areas that needed cleansing and amount of water consumed were significantly less in the SP/LHM than in the LHM group (P < 0.01). In SP/LHM (P = 0.01), endoscopy procedure duration was significantly longer. Although there was no significant difference in rate of detection of diminutive lesions between LHM and SP/LHM, the endoscopist carried out more biopsies in SP/LHM. This led to a higher rate of diagnosis of atrophic gastritis (P = 0.014) and intestinal metaplasia (P = 0.024). There was no significant difference in gag reflex (P = 0.604) and oxygenation during the endoscopy procedure for either group of patients. CONCLUSION: Routine use of premedication with simethicone/Pronase should be recommended during EGD with sedation.


Assuntos
Sedação Consciente/métodos , Detecção Precoce de Câncer/métodos , Endoscopia Gastrointestinal/métodos , Pré-Medicação/métodos , Pronase/farmacologia , Simeticone/farmacologia , Neoplasias Gástricas/diagnóstico , Adolescente , Adulto , Idoso , Antiespumantes/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Adulto Jovem
10.
Am J Cancer Res ; 7(6): 1238-1251, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28670488

RESUMO

Development of cancer metastasis is a key contributor to mortality in patients with colorectal cancer. High expression of RING-box 2 (RBX2) in cancer cells is known to play a key role in tumor progression. However, the role of RBX2 in colorectal cancer progression is not well elucidated. In this study, we silenced RBX2 via CRISPR/Cas9 in two colorectal cancer cell lines, HCT116 and SW480. RBX2 knockout attenuated proliferation, colony formation and enhanced sensitivity of colorectal cancer cells to paclitaxel treatment. Invasive property of HCT116 and SW480 cells was also attenuated by RBX2 silencing. We confirmed that increased RBX2 correlated with higher tumor cells growth and metastasis abilities by ectopic expression of RBX2 in HCT116 and SW480 cells. In vivo studies suggested that knockout of RBX2 inhibited xenografts growth and metastasis to lung tissue, whereas ectopic expression of RBX2 promoted these cellular functions. Mechanically, RBX2 induced gastric cancer cell growth and metastasis by activating mammalian target of rapamycin/S6 kinase 1 (mTOR/S6K1). Treatment of everolimus, the specific mTOR inhibitor, significantly attenuated RBX2-mediated cell proliferation and mobility in vitro. Taken together, these results revealed a novel role of RBX2 in colorectal cancer cell growth and metastasis via the mTOR pathway and suggested RBX2 may serve as a therapeutic target in colorectal cancer.

11.
Am J Transl Res ; 9(5): 2207-2218, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28559972

RESUMO

Colorectal cancer is one of the major health problems, with invade surrounding tissues, and migrate to distant organs being the most critical concern, thus identified metastasis associated hallmarks and more efficacious treatment are urgently needed. It found that forkhead box q1 (FOXQ1) is aberrant expression in variety of human cancers and FOXQ1 is involved in oncogenic pathways. However, the role of FOXQ1 has been unexplored in colorectal cancer metastasis to date. Here, expression of FOXQ1 was higher in colorectal cancer tissue samples and cancer cell lines than in normal colorectal tissue and cell lines. Further research suggested that FOXQ1 positively regulated cell proliferation in colorectal cancer and down-regulation of CDK6, extracellular regulated protein kinases 1/2 (ERK1/2) and mammalian target of rapamycin (mTOR). In corresponding to this result, over-expression of FOXQ1 significantly promoted colorectal cancer growth in vivo. Moreover, down regulation of FOXQ1 expression in colorectal carcinoma cell HCT116 and LOVO strikingly inhibits tumor growth in vivo. Finally, FOXQ1-dependent inhibition of colorectal cancer cell migration and invasion and down-regulation of focal adhesion kinase (FAK), phosphatidyl inositol 3-kinase (PI3K) phosphorylation, AKT (v-akt murine thymoma viral oncogene) phosphorylation and matrix metalloproteinase-2/9 (MMP-2/9) expression. These integrated efforts have identified FOXQ1 as a tumor promoter and might provide promising approaches for colorectal cancer metastasis treatment.

12.
Am J Cancer Res ; 6(9): 1935-1948, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27725900

RESUMO

Gastric carcinoma is one of the most lethal malignancies of cancers and its prognosis remains dismal due to the paucity of effective therapeutic targets. Herein, we showed that HRAS is markedly up-regulated in gastric carcinoma. Prognostic analysis indicated that HRAS expression might be a prognostic indicator for the survival of patients with gastric carcinoma. Ectopic expression of HRAS in gastric carcinoma cells accelerated proliferation, migration, invasion, angiogenesis, and clone formation ability of gastric carcinoma cells in vitro. Furthermore, HRAS over-expressing significantly promoted the tumorigenicity of gastric carcinoma cells in vivo whereas silencing endogenous HRAS caused opposite outcomes. Moreover, we demonstrated that HRAS enhanced gastric carcinoma aggressiveness by activating VEGFA/PI3K/AKT pathway and Raf-1 signaling. Together, our results provide new evidence that HRAS overexpression promotes the progression of gastric carcinoma and might represent a novel therapeutic target for its treatment.

13.
Sci Rep ; 5: 17516, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26620627

RESUMO

To identify clinicopathologic and treatment variables that could predict pathologic tumor response to short-term neoadjuvant chemotherapy (NAC) for patients with locally advanced gastric cancer. A retrospective analysis was conducted of 178 patients who underwent short-term NAC with EOX regimen followed by surgery from January 2008 to December 2010. Neoadjuvant treatment response was evaluated using tumor regression grade. Relationships between pathologic tumor response and clinicopathological factors were evaluated using logistic regression analysis. The benefits of regional arterial infusion chemotherapy were investigated separately. The postoperative pathological response rate was 46.1% (82/178) and 4 patients (2.2%) had complete pathological remission. Pathological response was significantly associated with tumor differentiation (P = 0.008), abnormal a-fetoprotein levels (P = 0.01) and administration approach to chemotherapy (intravenous versus regional arterial infusion chemotherapy) (P = 0.018). Most bone marrow toxicities, vomiting, nausea, alopecia, and fatigue were acceptable. Grade 3/4 toxicities were not commonly observed. The 3-year overall survival (OS) and recurrence free survival (RFS) were 67.0% and 53.0%, respectively. Regional arterial infusion NAC group had significantly better median RFS (48.0 versus 34.0 months) than the intravenous NAC group (P = 0.049). In conclusion, regional arterial infusion NAC can improve the pathological response rate of advanced gastric cancer treated with EOX regimen.


Assuntos
Infusões Intra-Arteriais/métodos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
14.
Oncotarget ; 6(42): 44563-78, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26575424

RESUMO

Most anti-angiogenic therapies currently being evaluated in clinical trials target vascular endothelial growth factor (VEGF) pathway, however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified formononetin as a novel agent with potential anti-angiogenic and anti-cancer activities. Formononetin demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor 2 (FGF2). In ex vivo and in vivo angiogenesis assays, formononetin suppressed FGF2-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of formononetin on different molecular components in treated endothelial cell, and found that formononetin suppressed FGF2-triggered activation of FGFR2 and protein kinase B (Akt) signaling. Moreover, formononetin directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer, formononetin showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Moreover, formononetin enhanced the effect of VEGFR2 inhibitor sunitinib on tumor growth inhibition. Taken together, our results indicate that formononetin targets the FGFR2-mediated Akt signaling pathway, leading to the suppression of tumor growth and angiogenesis.


Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Isoflavonas/farmacologia , Neovascularização Patológica , Inibidores de Proteínas Quinases/farmacologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Embrião de Galinha , Membrana Corioalantoide/irrigação sanguínea , Membrana Corioalantoide/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Indóis/farmacologia , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Fisiológica/efeitos dos fármacos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirróis/farmacologia , Ratos Sprague-Dawley , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sunitinibe , Fatores de Tempo , Carga Tumoral/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Am J Cancer Res ; 5(6): 2012-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26269760

RESUMO

Retinoic acid is an effective agent in the treatment of epithelial and hematological malignancies. The present study demonstrates that retinoic acid chalcone (RAC), an analogue of retinoic acid inhibits cell proliferation and induces apoptosis in HCT-15 and CT26.WT colon cancer cell lines. In HCT-15 cells the percentage of apoptotic cells increased from 32.4 ± 3, 45.0 ± 3 to 72.6 ± 5% respectively at 10, 15 and 20 µg/mL compared to 3.7% in control. Similarly in CT26.WT cells the percentage increased from 28.6 ± 3, 41.2 ± 3 to 65.4 ± 5% on treatment with 10, 15 and 20 µg/mL concentrations of RAC after 72 h compared to 2.9 ± 1% in control. Western blotting, fluorescence-activated cell sorting analysis and reverse transcription-PCR assays were used to investigate these effects. RAC inhibited the overexpression of COX-2, PGE2 and PGE2 receptor (EP1 and EP4) in the colon cancer cell lines. RAC mediated inhibition of cell growth and induction of apoptosis through COX-2 inhibition was also confirmed by treating the HCT-15 and CT26.WT colon cancer cells with COX-2 inhibitor, indomethacin and transfection of cells with COX-2 small interfering RNA. In nude mice with tumor xenografts, treatment with RAC-supplemented diet caused inhibition of COX-2, PGE2, and PGE2 receptors (EP1, EP3, and EP4) in tumors. Thus RAC can be a potential candidate for the treatment of colon cancer through the inhibition of COX-2 expression and subsequent inhibition of PGE2 and PGE2 receptors.

16.
World J Gastroenterol ; 21(3): 935-43, 2015 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-25624728

RESUMO

AIM: To investigate the prognostic factors after resection for hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC) and to assess the impact of different extents of lymphadenectomy on patient survival. METHODS: A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed. The patients were classified into groups according to the extent of lymphadenectomy (no lymph node dissection, sampling lymph node dissection and regional lymph node dissection). Clinicopathological characteristics and survival were reviewed retrospectively. RESULTS: The cumulative 1-, 3-, and 5-year survival rates were found to be 60%, 18%, and 13%, respectively. Multivariate analysis revealed that liver cirrhosis (HR = 1.875, 95%CI: 1.197-3.278, P = 0.008) and multiple tumors (HR = 2.653, 95%CI: 1.562-4.508, P < 0.001) were independent prognostic factors for survival. Recurrence occurred in 70 patients. The 1-, 3-, and 5-year disease-free survival rates were 36%, 3% and 0%, respectively. Liver cirrhosis (HR = 1.919, P = 0.012), advanced TNM stage (stage III/IV) (HR = 2.027, P < 0.001), and vascular invasion (HR = 3.779, P = 0.02) were independent prognostic factors for disease-free survival. Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection. Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status. CONCLUSION: The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC, and routine lymph node dissection is not recommended, particularly for those without lymph node metastasis.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia , Hepatite B/complicações , Excisão de Linfonodo , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/virologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/virologia , Distribuição de Qui-Quadrado , Colangiocarcinoma/mortalidade , Colangiocarcinoma/secundário , Colangiocarcinoma/virologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Hepatite B/diagnóstico , Hepatite B/mortalidade , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Seleção de Pacientes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
J Surg Res ; 193(1): 153-60, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25128925

RESUMO

BACKGROUND: To investigate the clinicopathologic characteristics of patients with both hepatitis B virus-surface antigen and hepatitis C virus antibody negative hepatocellular carcinoma (non-B non-C HCC [NBNC-HCC]) and examine the impact of occult hepatitis B virus infection (OBI) on patients' survival. METHODS: All patients with OBI were identified from a database of patients with NBNC-HCC who underwent surgical resection between January 1, 2006, and December 31, 2008. Their clinicopathologic and survival characteristics were compared with NBNC-HCC patients without OBI. RESULTS: Out of the 86 NBNC-HCC patients, 59 patients (68.6%) with OBI. A higher prevalence of hepatitis B core antigen positive rate, low platelet count, portal hypertension, and liver cirrhosis were observed in NBNC-HCC patients with OBI. The 1- and 3-y recurrence free survival rates were 66% and 25% in OBI group and 89% and 70% in the no OBI group, respectively (P < 0.001). The 1-, 3-, and 5-y overall survival rates were 86%, 55%, and 51% in OBI group and 93%, 85%, and 66% in no OBI group, respectively (P = 0.112). Multivariate analysis revealed that OBI (hazard ratio [HR] = 2.122; 95% confidence interval [CI], 1.086-4.149; P = 0.028), liver cirrhosis (HR = 2.411; 95% CI, 1.337-4.345; P = 0.003), and vascular invasion (HR = 5.858; 95% CI, 2.799-12.261; P < 0.001) were independent poor prognostic factors for recurrence free survival of patients with NBNC-HCC. CONCLUSIONS: NBNC-HCC patients with OBI had a poorer prognosis. OBI can be a useful predictor for recurrence in patients with NBNC-HCC after surgery.


Assuntos
Carcinoma Hepatocelular , Hepatectomia/mortalidade , Hepatite B Crônica/mortalidade , Hepatite B Crônica/cirurgia , Neoplasias Hepáticas , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Antígenos da Hepatite C/sangue , Hepatite C Crônica/mortalidade , Hepatite C Crônica/cirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva , Estudos Retrospectivos , Estudos Soroepidemiológicos , Análise de Sobrevida
18.
World J Gastroenterol ; 20(43): 16268-74, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25473182

RESUMO

AIM: To explore the potential correlation between insulin-like growth factor receptor-1 (IGF-1R) expression and rectal cancer radiosensitivity. METHODS: Eighty-seven rectal cancer patients (cTNM I-III) treated in our department between January 2011 and December 2012 were enrolled. All subjects were treated with preoperative radiotherapy and radical resection of rectal carcinoma. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to detect IGF-1R expression in pre-treatment and postoperative colorectal cancer specimens. Radiosensitivity for rectal cancer specimens was evaluated by observing rectal carcinoma mass regression combined with fibrosis on HE staining, degree of necrosis and quantity of remaining tumor cells. The relative IGF-1R expression was evaluated for association with tumor radiosensitivity. RESULTS: Immunohistochemistry showed diffuse IGF-1R staining on rectal cancer cells with various degrees of signal density. IGF-1R expression was significantly correlated with cTNM staging (P = 0.012) while no significant association was observed with age, sex, tumor size and degree of differentiation (P = 0.424, 0.969, 0.604, 0.642). According to the Rectal Cancer Regression Grades (RCRG), there were 31 cases of RCRG1 (radiation sensitive), 28 cases of RCRG2 and 28 cases of RCRG3 (radiation resistance) in 87 rectal cancer subjects. IGF-1R protein hyper-expression was significantly correlated with a poor response to radiotherapy (P < 0.001, r = 0.401). RT-PCR results from pre-radiation biopsy specimens also showed that IGF-1R mRNA negative group exhibited a higher radiation sensitivity (P < 0.001, r = 0.497). Compared with the pre-radiation biopsy specimens, the paired post-operative specimens showed a significantly increased IGF-1R protein and mRNA expression in the residual cancer cells (P < 0.001, respectively). CONCLUSION: IGF-1R expression level may serve as a predictive biomarker for radiosensitivity of rectal cancer before preoperative radiotherapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma/radioterapia , Terapia Neoadjuvante , Radioterapia de Intensidade Modulada , Receptores de Somatomedina/metabolismo , Neoplasias Retais/radioterapia , Biomarcadores Tumorais/genética , Biópsia , Carcinoma/química , Carcinoma/patologia , Carcinoma/cirurgia , Feminino , Fibrose , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Necrose , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Tolerância a Radiação , Radioterapia Adjuvante , Receptor IGF Tipo 1 , Receptores de Somatomedina/genética , Neoplasias Retais/genética , Neoplasias Retais/metabolismo , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
19.
Mol Med Rep ; 10(1): 486-90, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24788673

RESUMO

The present study aimed to examine the effects of recombinant human growth hormone (rhGH) on the sensitivity of a colorectal cancer cell line to radiotherapy, and to investigate its association with DNA damage and repair. Flow cytometry and immunofluorescence were employed to detect growth hormone receptor (GHR) expression in nine human colorectal cancer cell lines. A colony forming assay was performed to measure the colorectal cancer cell proliferation post­radiotherapy, as an indicator of radiotherapy sensitivity. The comet assay results were interpreted as an indicator of radiotherapy­induced DNA damage, and growth arrest and DNA damage 45 (GADD45) and apurinic/apyrimidinic endonuclease (APEN) protein expression were quantified with western blot analysis from the same cell lines. The results demonstrated that the colony­forming efficiency (CFE) was significantly increased in HCT­8 cells subject to radiotherapy and rhGH pretreatment compared with the cells treated with radiotherapy alone, in a dose­dependent manner (0­100 mg/l). This effect was enhanced under high doses of radiation (8 Gy; 52.1±2.9 vs. 21.0±2.7; P<0.001) and was ameliorated with GHR neutralizing antibody exposure. By contrast, rhGH pre­incubation did not change the colony formation rate in GHR(­) LOVO cells. rhGH intervention reduced the early HCT­8 cell DNA damage (21.53±2.88 vs. 36.56±3.93; P=0.003) as well as the following plateau phase, compared with cells treated with radiotherapy alone (5.5±0.42 vs. 9.07±0.84; P=0.012). rhGH upregulated GADD45 and APEN protein expression, which is associated with cellular stress responses and DNA damage repair (P=0.007). The results suggest that rhGH is able to protect colorectal cancer cells from radiation through the interaction with GHR, which is associated with the promotion of DNA damage repair activity.


Assuntos
Reparo do DNA/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Ensaio Cometa , Dano ao DNA/efeitos da radiação , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Raios gama , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas GADD45
20.
Ai Zheng ; 25(9): 1162-7, 2006 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-16965663

RESUMO

BACKGROUND & OBJECTIVE: Growth hormone (GH) could activate pathways involved in DNA repair process by binding to growth hormone receptor (GHR), which is thought as one of the mechanisms of radioprotection. This study was to evaluate the correlation of GHR expression to radiosensitivity of rectal cancer. METHODS: The expression of GHR in biopsy specimens from 98 rectal cancer patients before preoperative irradiation and postoperative specimens was detected by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). Radiosensitivity was evaluated according to Rectal Cancer Regression Grading. RESULTS: IHC revealed that GHR overexpression was positively correlated to poor response to radiotherapy (P<0.001, rs=0.399); RT-PCR also showed that radiosensitivity was significantly higher in GHR mRNA-negative group than in GHR mRNA-positive group (P<0.001, rs=0.398). Compared with the biopsy specimens before preoperative irradiation, the paired postoperative specimens showed significantly increased GHR expression in residual cancer cells (P<0.001). CONCLUSION: Detection of GHR expression before preoperative irradiation may predict radiosensitivity of rectal cancer.


Assuntos
Tolerância a Radiação , Receptores da Somatotropina/biossíntese , Neoplasias Retais/metabolismo , Neoplasias Retais/radioterapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceleradores de Partículas , Cuidados Pré-Operatórios , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Radioterapia de Alta Energia , Receptores da Somatotropina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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