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1.
World J Gastroenterol ; 30(11): 1572-1587, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38617453

RESUMO

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported. AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT. METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure. RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT. CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.


Assuntos
Antifibrinolíticos , Doença de Crohn , Microbiota , Humanos , Aminoácidos , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Escherichia coli , Metagenoma , Estudos Prospectivos
2.
World J Clin Cases ; 12(3): 596-600, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322460

RESUMO

BACKGROUND: Guidewire slippage into the peritoneal cavity during clinical operations is extremely rare. Therefore, this paper aims to report a successful case of guidewire removal using transgastric natural orifice transluminal endoscopic surgery (NOTES). The goal is to enhance physicians' understanding of the management plan for this unique scenario and provide a valuable reference for clinical practice. CASE SUMMARY: A 64-year-old man presented with abdominal distension and was diagnosed with cirrhosis combined with massive ascites. To proceed with treatment, the patient underwent ultrasound-guided peritoneal puncture and underwent catheterization and drainage. Unfortunately, a 0.035-inch guidewire slipped into the abdominal cavity during the procedure. Following a comprehensive evaluation and consultation by a multidisciplinary team, the guidewire was successfully removed using NOTES. CONCLUSION: This case highlights the potential consideration of transgastric NOTES removal when encountering a foreign body, such as a guidewire, within the abdominal cavity.

3.
BMC Gastroenterol ; 23(1): 249, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488516

RESUMO

OBJECTIVES: This study aimed to evaluate the efficacy, adverse events, patient compliance, and cost of dual therapy with Ilaprazole-amoxicillin (IA) at high dose versus Ilaprazole-amoxicillin-furazolidone-bismuth (IAFB) quadruple therapy for the Helicobacter pylori (H.pylori) infection among Chinese patients. METHODS: 200 patients who had tested positive for H. pylori and undergoing upper gastrointestinal endoscopy after being diagnosed with chronic gastritis participated in this open-label randomized controlled clinical trial. Patients were randomized to Group A and Group B: the 14-day IA dual treatment group (101) and IAFB quadruple treatment group (99). The 13 C urea breath test was conducted to determine whether H. pylori had been eliminated 4-6 weeks after the treatment. Eradication rates, drug-related adverse events, patient compliance, and drug costs were compared between the two treatment groups. RESULTS: Eradication rates in group A were 92.1% and 94.9%, depending on the intention-to-treat (ITT), per-protocol (PP), respectively, which was similar to group B (91.9% and 93.6%). There was no significant difference observed in adverse events between the two groups (P = 0.518). Interestingly, compliance was significantly higher in group A compared to the group B (P = 0.031). In addition, drug costs were significantly lower for group A in comparison to the group B. CONCLUSIONS: IA dual therapy was found to be equally effective, safer and less costly than IAFB quadruple therapy. Therefore, these therapies can be potentially considered as first-line regimens for empirical treatment.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina , 2-Piridinilmetilsulfinilbenzimidazóis , Bismuto , Furazolidona
4.
Artigo em Inglês | MEDLINE | ID: mdl-36874616

RESUMO

Gastric cancer (GC) is a common digestive tract tumor. Due to its complex pathogenesis, current diagnostic and therapeutic effects remain unsatisfactory. Studies have shown that KLF2, as a tumor suppressor, is downregulated in many human cancers, but its relationship and role with GC remain unclear. In the present study, KLF2 mRNA levels were significantly lower in GC compared to adjacent normal tissues, as analyzed by bioinformatics and RT-qPCR, and correlated with gene mutations. Tissue microarrays combined with immunohistochemical techniques showed downregulation of KLF2 protein expression in GC tissue, which was negatively correlated with patient age, T stage, and overall survival. Further functional experiments showed that knockdown of KLF2 significantly promoted the growth, proliferation, migration, and invasion of HGC-27 and AGS GC cells. In conclusion, low KLF2 expression in GC is associated with poor patient prognosis and contributes to the malignant biological behavior of GC cells. Therefore, KLF2 may serve as a prognostic biomarker and therapeutic target in GC.

5.
World J Gastroenterol ; 29(1): 144-156, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36683714

RESUMO

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.


Assuntos
Microbioma Gastrointestinal , Encefalopatia Hepática , Probióticos , Animais , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Disbiose/complicações , Cirrose Hepática/complicações , Probióticos/uso terapêutico , Encéfalo
6.
Expert Rev Gastroenterol Hepatol ; 16(8): 797-807, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35942803

RESUMO

BACKGROUND: Sleep disturbances are prevalent in patients with minimal hepatic encephalopathy (MHE). This study aimed to evaluate the association between sleep disturbances and altered gut microbiota in patients with MHE caused by hepatitis B-related liver cirrhosis. RESEARCH DESIGN AND METHODS: Ninety-eight and 45 patients with MHE were included in exploration and validation cohorts, respectively. Sleep disturbances were assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Microbiota in fecal samples were analyzed via amplicon sequencing of bacterial 16S ribosomal RNA genes. RESULTS: The gut microbiomes of MHE patients with sleep disturbances were characterized by lower bacterial diversity and distinct bacterial composition. Relative abundances of Streptococcus salivarius and Veillonella were independent predictors of sleep disturbances in MHE patients and well-distinguished MHE patients with and without sleep disturbances in both the exploration and validation cohorts. Moreover, the relative abundances of S. salivarius were positively correlated with plasma ammonia levels, and functional modules associated with protein digestion and absorption and lipopolysaccharide biosynthesis were enriched in the microbiomes of MHE patients with sleep disturbances. CONCLUSIONS: Both S. salivarius and Veillonella were associated with sleep disturbances in patients with MHE caused by hepatitis B-related liver cirrhosis.


Assuntos
Microbioma Gastrointestinal , Encefalopatia Hepática , Hepatite B , Transtornos do Sono-Vigília , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Hepatite B/complicações , Hepatite B/diagnóstico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia
7.
Scand J Gastroenterol ; 57(9): 1066-1069, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35348416

RESUMO

OBJECTIVES: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication of liver cirrhosis. Both EncephalApp Stroop test (EncephalApp) and electronic number connection test-A (eNCT-A) are novel computerised psychometric tests for MHE screening. We aimed to compare the efficiency, convenience, accessibility, and acceptability of EncephalApp with that of eNCT-A for MHE screening in cirrhotic patients. METHODS: Ninety-five patients with hepatitis B-induced liver cirrhosis were included and respectively tested by the psychometric hepatic encephalopathy score (PHES), EncephalApp, and eNCT-A. Using PHES as the gold standard for MHE diagnosis, the efficiency of EncephalApp and eNCT-A for MHE screening were respectively analysed by the receiver operating characteristic (ROC) curve, and the areas under the ROC curve (AUROC) were compared. The convenience, accessibility, and acceptability of PHES, EncephalApp and eNCT-A were respectively evaluated by the 5-point Likert scale. RESULTS: Fifty-two (55%) of included cirrhotic patients were diagnosed with MHE. The EncephalApp had a sensitivity of 84.6%, a specificity of 74.4%, and an AUROC of 0.836. Meanwhile, the eNCT-A had a sensitivity of 78.8%, a specificity of 83.7%, and an AUROC of 0.845. No significant difference in AUROC was detected between the EncephalApp and eNCT-A (p = .453). Compared with the EncephalApp, the eNCT-A presented better convenience and higher acceptability in cirrhotic patients undergoing MHE screening (p = .019 and p < .001, respectively). CONCLUSIONS: As with the EncephalApp, the eNCT-A will be a potential home monitoring and point-of-care tool for cirrhotic patients at high risk of MHE.


Assuntos
Encefalopatia Hepática , Eletrônica , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Cirrose Hepática/complicações , Psicometria , Teste de Stroop
8.
Hepatol Res ; 51(8): 839-849, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34185942

RESUMO

AIM: Minimal hepatic encephalopathy (MHE) is a common neuropsychiatric complication of liver cirrhosis and portosystemic shunt. The inhibitory control test (ICT) is a novel computerized psychometric test for MHE diagnosis, but its efficiency has yet to be confirmed. This study aimed to systematically review the existing evidence concerning the ICT application and then evaluate the efficiency of ICT for MHE diagnosis in clinical practice. METHODS: A comprehensive search of published works was carried out to identify reports concerning the ICT for MHE diagnosis between January 2000 and December 2020. The pooled sensitivity, specificity, and diagnostic odds ratio of ICT for MHE diagnosis were calculated using a random or fixed effect model. The summary receiver operator characteristic (sROC) curve was constructed, and the area under the sROC curve was calculated. Metaregression and subgroup analyses were used to identify the source of heterogeneity. Publication bias was evaluated using the Deeks funnel plot asymmetry test. RESULTS: Twelve studies were included in this systematic review, and nine studies enrolling 1022 patients were included in the final meta-analysis. The ICT had a pooled sensitivity, specificity, and DOR of 83%, 64%, and 9, respectively. The area under the sROC curve was 0.79. The metaregression analysis indicated that different locations of studies (relative diagnostic odds ratio, 12.65; p = 0.02) were identified as the source of heterogeneity. No significant publication bias was observed. CONCLUSIONS: The ICT has a high sensitivity and moderate specificity for MHE diagnosis, and it can be used as a primary diagnostic method for MHE.

9.
World J Clin Cases ; 8(16): 3377-3389, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32913845

RESUMO

Minimal hepatic encephalopathy (MHE) is a critical neurocognitive complication of decompensated liver cirrhosis and portosystemic shunting, which results in a wide range of cognitive deficits including impairments in working attention, psychomotor speed, and executive function. Current guidelines have recommended paper-and-pencil psychometric tests for the diagnosis of MHE. Most high-risk cirrhotic patients are required to be examined; however, paper-and-pencil psychometric tests are neither convenient nor rapid to perform in the clinic. Recently, novel computerized psychometric tests, including the inhibitory control test, EncephalApp Stroop App, and critical flicker frequency, have been proven to be rapid, effective, and convenient methods for screening MHE in clinical practice and for identifying high-risk cirrhotic patients for further validation using rigid neuropsychometric examinations. However, diagnostic accuracy of these tests is influenced by educational background, age, and cultural differences. This review summarizes clinical evidence of the application of novel computerized psychometric tests for screening MHE.

10.
Saudi J Gastroenterol ; 26(3): 120-128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32270775

RESUMO

BACKGROUND/AIM: A novel computerised Stroop test- EncephalApp Stroop App (EncephalApp) has good diagnostic validity for minimal hepatic encephalopathy (MHE) in cirrhotic patients. The Stroop test is correlated with sleep disturbances which are common, and severely affects health-related quality of life in cirrhotic patients with MHE. We evaluated the relationship between sleep quality and EncephalApp results in patients with MHE due to hepatitis B-induced liver cirrhosis. PATIENTS AND METHODS: We enrolled 180 adult patients with hepatitis B-induced cirrhosis. All patients were tested using the psychometric hepatic encephalopathy score (PHES) and EncephalApp. We analysed the diagnostic validity of EncephalApp for MHE using PHES as the gold standard for reference. The sleep quality of included patients was evaluated using the Pittsburgh Sleep Quality Index (PSQI). The predictive factors for poor sleep quality were analysed using backwards conditional stepwise logistic regression analysis. RESULTS: Ninety-eight patients (54.4%) were diagnosed with MHE by PHES. Receiver operating characteristic (ROC) curve analysis showed that the threshold value of EncephalApp for MHE diagnosis was 225.60 s. EncephalApp showed 85.2% sensitivity and 77.3% specificity for diagnosing MHE; the area under the ROC curve was 0.864. PSQI scores of cirrhotic patients with MHE were significantly lower than those without MHE (P < 0.05). Child Turcotte Pugh grades (Odds ratio [OR] = 2.11 [1.55-2.85], P < 0.01) and the total Off-time plus On-time of EncephalApp (OR = 4.14 [1.95-6.29], P < 0.01) were independent predictors of poor sleep quality in MHE patients. CONCLUSIONS: The total Off-time plus On-time of EncephalApp predicts poor sleep quality in patients with MHE due to hepatitis B-induced cirrhosis.


Assuntos
Encefalopatia Hepática , Hepatite B , Cirrose Hepática , Transtornos do Sono-Vigília , Encefalopatia Hepática/diagnóstico , Hepatite B/complicações , Humanos , Cirrose Hepática/complicações , Psicometria , Qualidade de Vida , Curva ROC , Transtornos do Sono-Vigília/complicações
12.
Clin Res Hepatol Gastroenterol ; 39(6): 665-73, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26216028

RESUMO

Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of acute and chronic liver dysfunction, and is characterized by a spectrum that ranges from mild neuropsychological disturbances to coma. Although ammonia plays a critical role in the pathogenesis of HE, the plasma concentrations of ammonia and manifest symptoms of HE are not always consistent in patients with HE. Recently, a substantial body of evidence has indicated that inflammation acts in concert with ammonia in the pathogenesis of HE. Meanwhile, emerging novel and potential therapeutic strategies, including N-acetylcysteine, hypothermia, minocycline, non-steroidal anti-inflammatory drugs, tumour necrosis factor-alpha antagonists and p38 inhibitors, have been reported to ameliorate systemic inflammation and neuroinflammation, improve or reverse neuropsychiatric manifestations, and prevent the onset and progression of HE in patients and/or animal models of acute or chronic liver failure. These results point to the possible therapeutic utility of decreasing inflammation in the treatment of HE, and translation of these experimental results to the clinic may provide novel and promising therapeutic approaches for patients with HE secondary to acute or chronic liver failure. This review will provide an overview of these potential targeted therapies in the prophylaxis and treatment of HE.


Assuntos
Encefalopatia Hepática/tratamento farmacológico , Inflamação/tratamento farmacológico , Encefalopatia Hepática/etiologia , Humanos , Inflamação/complicações
13.
Zhonghua Zhong Liu Za Zhi ; 29(4): 258-61, 2007 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-17760250

RESUMO

OBJECTIVE: To investigate the binding effect of the short peptide SY1 to the multidrug-resistant gastric cancer cell line SGC7901/VCR cells and its reversing effect on those cancer cells. METHODS: The cultured cells were divided into two groups named SGC7901 and SGC7901/VCR. The SGC7901/VCR group was co-cultured with vincristine (VCR). SY1 was obtained from cyclic 7-mer peptide library by differential screening. Immunofluorescence technique was used to detect the capacity of SY1-containing positive phage specifically binding to SGC7901/VCR cells, compared with that of the negative phage and unrelated phage. MTT assay in vitro was performed to analyze the alteration of drug resistance of SGC7901/ VCR cells, using the positive phages and the chemically synthesized SY1 peptide. Flow cytometry assay was performed to detect the accumulation and retention of adriamycin (ADM) in the SGC7901/VCR cells. RESULTS: Immunofluorescence analysis showed that the SY1-containing positive phages could bind to the SGC7901/VCR cell surface but not to its parent cell line SGC7901 cells. The unrelated phage and negative phage did not bind to SGC7901/VCR cells. These results indicated that SY1 could specifically bind to SGC7901/VCR cells. MTT assay in vitro showed that the survival rate of SGC7901/VCR cells was reduced considerably by the positive phages and the chemically synthesized SY1 peptide (P <0. 05), indicating that SY1 enhanced the sensitivity of SGC7901/VCR cells to chemotherapeutic drug VCR. Flow-cytometric detection showed that SY1 enhanced the accumulation of ADM in the SGC7901/VCR cells, compared with that of the negative phages and the unrelated phages (P <0.05). CONCLUSION: SY1 not only is able to bind to SGC7901/VCR cells specifically, but also can partly reverse the resistance of SGC7901/VCR cell line to chemotherapeutic drug VCR. Those findings might be important to open a new approach to reverse the gastric cancer MDR.


Assuntos
Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Peptídeos Cíclicos/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antibióticos Antineoplásicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Bacteriófagos/genética , Sítios de Ligação , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Citometria de Fluxo , Imunofluorescência , Humanos , Biblioteca de Peptídeos , Peptídeos Cíclicos/genética , Ligação Proteica , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Vincristina/farmacologia
14.
Zhonghua Yi Xue Za Zhi ; 87(22): 1570-5, 2007 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-17785115

RESUMO

OBJECTIVE: To investigate the potential role of inhibitor of DNA binding/differentiation 1 (Id1) in cyclooxygenase-2 (COX-2) mediated angiogenesis in gastric cancer. METHODS: Two human gastric cancer sub-cell lines (SGC7901/COX-2 and SGC7901/COX-2RNAi) highly expressing COX-2 and COX-2 RNAi respectively were established. Western blotting and RT-PCR were performed to detect the protein and mRNA expression levels of Id1 in these transfectants. ELISA was performed to detect the levels of VEGF protein in the supernatants of these cells. Humane umbilical vein endothelial cells of the line HU-LT were cultured in condition medium, supernatant of SGC7901/COX2 cells transfected with COX-2 sense strand, COX-2 SiRNA and Id1. MTT assay was used to examine the proliferation ability of these cells. Suspensions of SGC7901/COX-2 and SGC7901/COX-2RNAi cells were injected subcutaneously to nude mice respectively. Eight weeks later the mice were killed and the tumors were taken out to undergo immunohistochemistry and detection of mcrovessel density (MVD). RESULTS: Western blotting and RT-PCR showed that the expression levels of COX-2 protein and mRNA, as well as those of Id1 in the SGC7901/COX-2 cells were high, and the expression level of Id1 was down-regulated in the SGC7901/COX-2RNAi cells transfected with Id1 RNAi. The VEGF level of the SGC7901/COX-2 cells was 2060 +/- 42, significantly higher than that of the control SGC7901/PC cells (1248 +/- 28, P = 0.000) and VEGF level of the supernatant of then SGC7901/COX-2 RNAi cells was 1024 +/- 20, significantly lower than that of the SGC7901/COX-2/PC cells (2033 +/- 27, P = 0.000). The proliferation rate of the HU-LT cells cultured in SGC7901/COX-2 condition medium was higher than that of the HU-LT cells cultured in SGC7901/COX-2RNAi condition medium. The increase of VEGF in the SGC7901/COX-2 and the effect of contribution to the proliferation of HU-LT were both abrogated when Id1 was knocked out in the SGC7901/COX-2. The tumor weight of the COX-2 RNAi group was (353 +/- 12) mg, significantly lower than that of the SGC7901/COX-2 group [(1020 +/- 91) mg, P = 0.038]. The MVD of the tumor of the COX-2 RNAi group was 8.8 +/- 1.6, significantly lower than that of the SGC7901/COX-2 group (20 +/- 1.7, P = 0.001). CONCLUSION: COX-2 can stimulate VEGF and enhance the proliferation of endothelial cells by upregulating Id1, and blocking this pathway may be helpful to the tumor therapeutics, so COX-2 and Id1 can be exploited as therapeutic targets of gastric cancer.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Proteína 1 Inibidora de Diferenciação/metabolismo , Neovascularização Patológica/patologia , Neoplasias Gástricas/patologia , Animais , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/metabolismo , Ciclo-Oxigenase 2/genética , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/fisiologia , Camundongos , Camundongos Nus , Neoplasias Experimentais/irrigação sanguínea , Neoplasias Experimentais/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/irrigação sanguínea , Transfecção , Transplante Heterólogo , Fator A de Crescimento do Endotélio Vascular/biossíntese
16.
Zhonghua Yi Xue Za Zhi ; 86(10): 659-63, 2006 Mar 14.
Artigo em Chinês | MEDLINE | ID: mdl-16681920

RESUMO

OBJECTIVE: To screen and identify peptides that binds specifically to gastric cancers cells with high metastasis to peritoneum so as to find appropriate vectors for targeting therapy for cancer. METHODS: Human gastric cancer cells of the line GC9811 and those with high metastasis to peritoneum of the line GC9811-P were co-incubated with the 12-mer bacteriophage random peptide library. After 3 round of repeated screening, phage clones were collected. Forty internalized phage single-stranded DNA that specifically binding to the GC98112-P cells were sequenced. GC9811 and GC9811-P cells were co-inoculated with 5 peptides with the N end marked with fluorescein isothiocyanate (FITC) and 1 un-related peptide not binding to GC9811 and GC9811-P cells. Fluorescence microscopy, ELISA, and flow cytometry were used to detect the binding activity. BALB/cnu/nu mice were inoculated intraperitoneally with GC9811 and GC9811-P cells and then randomly divided into. 2 equal groups: experimental group, inoculated with the peptide PIII-FITC and control group (inoculated with un-related peptide PC-FITC. Forty-eight hours later the mice were killed and the peritoneum and tumor masses in different organs were collected and under fluorescence microscopy. RESULTS: DNA sequencing showed that 45% (18/45) of the isolated phages displayed repeated sequence SMSIASPYIALE, and SMSI was defined as a conservative motif. Obvious fluorescence was seen in the GC9811-P cells co-incubated with PIII-FITC and weak fluorescence was seen in the GC9811 cells co-incubated with PIII-FITC. Un-marked un-related peptide PC and PIII-FITC did not influenced the fluorescence staining of the GC9811-P cells, however, no fluorescence could be seen in the GC9811-P cells co-incubated with un-marked PIII and PIII-FITC. The fluorescence positive cell rate was 5.9% in the GC9811 cells co-incubated with PIII-FITC, and was 90.2% in the GC9811-P cells co-incubated with PIII-FITC. The fluorescence positive cell rates of the GC9811 cells and GC9811-P cells co-incubated with PC-FITC were 10.1% and 9.9% respectively 10.1% and 9.9% respectively. The fluorescence strength of the GC9811-P cells co-incubated with PIII-FITC was significantly greater than that of the GC9811-P cells co-incubated with PC-FTIC at any time-point and dose (all P < 0.01), and increased along with the increase of co-incubation time and dose of PIII-FITC. The peritoneal tumor tissues caused by the GC9811-P cells of the mice showed strong fluorescence and those caused by GC9811 cells only showed very weak fluorescence. Weak fluorescence could be seen in the tumor masses in the lymph nodes, liver, and muscle of the mice inoculated with GC9811-P cells and was not seen in the tissues of the mice inoculated with GC9811 cells. CONCLUSION: The sequence SMSIASPYIALE that specifically binds to human gastric cancer cells with high metastasis has been screened that has the potential to be used as a marker and targeting vector in diagnosis and treatment of gastric cancer.


Assuntos
Biblioteca de Peptídeos , Peptídeos/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Sequência de Aminoácidos , Animais , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia de Fluorescência , Transplante de Neoplasias , Neoplasias Experimentais/metabolismo , Peptídeos/genética , Neoplasias Peritoneais/metabolismo , Ligação Proteica , Neoplasias Gástricas/metabolismo
17.
Zhonghua Yi Xue Za Zhi ; 86(46): 3260-3, 2006 Dec 12.
Artigo em Chinês | MEDLINE | ID: mdl-17313805

RESUMO

OBJECTIVE: To evaluate the preventive potential of intraoperative or early postoperative local administration of peptide PIII into the abdominal cavity against peritoneal carcinomatosis. METHODS: Human gastric cancer cells of the line GC9811 were inoculated subcutaneously into nude mice to cause subcutaneous carcinoma. The 8th generation cancer was taken out to isolate the cancer cells to be inoculated into the serous membrane at the greater curvature of the stomach. Forty-eight nude BALB/C-nu/nu mice underwent implantation of the 8th generation cancer cells into the serous membrane at the greater curvature of the stomach via minilaparotomy so as to establish models of peritoneal carcinoma The 48 mice were randomly divided into 3 equal groups: Group 1 (control group); Group 2, undergoing intraperitoneal perfusion of 100 microg of peptide PIII, and post-operative intraperitoneal perfusion of 2 mg/kg peptide PIII twice; and Group 3, undergoing post-operative intraperitoneal perfusion of 100 microg/kg peptide PIII twice. Six mice in every group were sacrificed on the day 23 to undergo pathological examination. The other mice in every group were used to evaluate the survival rate. The tumor-bearing mice showing manifestations of failure were killed to undergo pathology. RESULTS: The weight of individual tumor was not significantly different among the 3 groups. The number of peritoneal metastatic nodules of Group 2 was (9.2 +/- 1.3), significantly less than those of Group 1 and 3 [(126.3 +/- 9.6) and (64.2 +/- 8.3) respectively, both P < 0.01]. The number of metastatic nodules > 2 mm of Group 2 was 1.6 +/- 0.2, significantly less then those of Groups 1 and 3 [(51.2 +/- 3.6) and (21.7 +/- 4.9) respectively, both P < 0.01]. The survival rate of Group 2 was significantly longer than those of Groups 1 and 3 (both P < 0.01). CONCLUSION: Peptide PIII does not significantly inhibit the growth of GC, but significantly reduce the peritoneal metastasis of GC. An ideal targeting chemotherapy, intra-operative application of peptide PIII into the abdominal cavity plus intraperitoneal perfusion is an attractive and promising strategy to prevent peritoneal metastasis of GC.


Assuntos
Peptídeos/uso terapêutico , Neoplasias Peritoneais/prevenção & controle , Neoplasias Gástricas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Injeções Intraperitoneais , Cuidados Intraoperatórios , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Inoculação de Neoplasia , Peptídeos/administração & dosagem , Neoplasias Peritoneais/secundário , Cuidados Pós-Operatórios , Neoplasias Gástricas/patologia
18.
Zhonghua Zhong Liu Za Zhi ; 27(7): 397-400, 2005 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16188121

RESUMO

OBJECTIVE: By means of phage-display technique, to screen polypeptides that specifically bind to human gastric cancer with high metastatic potential to peritoneum. METHODS: Two human gastric cancer cell lines were used: GC9811-P with high metastatic potential to peritoneum and its wild type parental GC9811, to carry out subtractive screening with a phage display-12 peptide library. RESULTS: After three rounds of screening, 40 phage clones bond to GC9811-P cells were randomly selected. When injected into the peritoneal cavity of nude mice, 6 of the 40 clones did not bind to mouse peritoneum as examined by immunohistochemical staining. They were considered to be capable of binding specifically to GC9811-P cells. Sequence analysis revealed two different exogenous peptides: TLNINRLILPRT and SMSI(X)SPYI(XXX). CONCLUSION: Two peptides have been obtained that specifically bind to a gastric cancer cell variant GC9811-P, which easily disseminates to the peritoneum. Whether or not they could block GC9811-P metastasis to peritoneum in vivo remains to be determined.


Assuntos
Biblioteca de Peptídeos , Peptídeos/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Análise Serial de Proteínas/métodos , Ligação Proteica , Sensibilidade e Especificidade , Neoplasias Gástricas/metabolismo
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