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1.
World J Gastrointest Oncol ; 16(3): 1029-1045, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38577446

BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

3.
World J Clin Cases ; 11(32): 7905-7910, 2023 Nov 16.
Article En | MEDLINE | ID: mdl-38073693

BACKGROUND: Gastric duplication cysts are very rare disease that are mainly diagnosed by endoscopic ultrasonographic fine-needle aspiration biopsy. In the past, this disease was usually treated with traditional surgery and rarely with minimally invasive endoscopic surgery. However, minimally invasive endoscopic therapy has many advantages, such as no skin wound, organ preservation, postoperative pain reduction, early food intake, fewer postoperative complications, and shorter post-procedure hospitalization. CASE SUMMARY: We report a case of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) combined with lauromacrogol sclerotherapy for pyloric obstruction due to gastric duplication cysts. CONCLUSION: EUS-FNA combined with lauromacrogol sclerotherapy provides a new option for the treatment of gastrointestinal duplication cysts.

4.
BMC Surg ; 23(1): 147, 2023 Jun 02.
Article En | MEDLINE | ID: mdl-37264328

BACKGROUND: There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms. METHODS: This study retrospectively analyzed rectal neuroendocrine neoplasm patients diagnosed and treated at the Fourth Hospital of Hebei Medical University from February 2007 to May 2021. The clinicopathological characteristics of rectal multiple neuroendocrine neoplasms were summarized and analyzed in combination with 14 studies on rectal multiple neuroendocrine neoplasms. RESULTS: The incidence of RM-NENs accounted for 3.8% of all R-NENs in this study. The number of tumors varied to some extent, the size of tumors was basically no more than 10 mm, and there were more G1 grade tumors. In the analysis of 46 cases with known lymph node metastasis, the difference in lymph node metastasis rate between the number of tumors < 8 and ≥ 8 was statistically significant (p = 0.002). CONCLUSIONS: The incidence of rectal multiple neuroendocrine neoplasms accounted for 3.8% of all rectal neuroendocrine neoplasms. For rectal multiple neuroendocrine neoplasms, the lymph node metastasis rate was higher when the number of tumors was ≥ 8. The influence of the number of tumors on lymph node metastasis should be considered in the selection of treatment.


Neuroendocrine Tumors , Rectal Neoplasms , Humans , Prognosis , Lymphatic Metastasis , Retrospective Studies , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/pathology , Rectal Neoplasms/diagnosis , Rectal Neoplasms/epidemiology , Rectal Neoplasms/pathology
5.
Therap Adv Gastroenterol ; 16: 17562848231177156, 2023.
Article En | MEDLINE | ID: mdl-37274299

Background: Previous studies have identified useful endoscopic ultrasonography (EUS) features to predict the malignant potential of gastrointestinal stromal tumors (GISTs). However, the results of the studies were not consistent. Artificial intelligence (AI) has shown promising results in medicine. Objectives: We aimed to build a risk stratification EUS-AI model to predict the malignancy potential of GISTs. Design: This was a retrospective study with external validation. Methods: We developed two models using EUS images from two hospitals to predict the GIST risk category. Model 1 was the four-category risk EUS-AI model, and Model 2 was the two-category risk EUS-AI model. The diagnostic performance of the models was validated with external cohorts. Results: A total of 1320 images (880 were very low-risk, 269 were low-risk, 68 were intermediate-risk, and 103 were high-risk) were finally chosen for building the models and test sets, and a total of 656 images (211 were very low-risk, 266 were low-risk, 88 were intermediate-risk, and 91 were high-risk) were chosen for external validation. The overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the four-category risk EUS-AI model in the external validation sets by tumor were 74.50%, 55.00%, 79.05%, 53.49%, and 81.63%, respectively. The accuracy, sensitivity, specificity, PPV, and NPV for the two-category risk EUS-AI model for the prediction of very low-risk GISTs in the external validation sets by tumor were 86.25%, 94.44%, 79.55%, 79.07%, and 94.59%, respectively. Conclusion: We developed a EUS-AI model for the risk stratification of GISTs with promising results, which may complement current clinical practice in the management of GISTs. Registration: The study has been registered in the Chinese Clinical Trial Registry (No. ChiCTR2100051191).

7.
Dis Markers ; 2023: 9226712, 2023.
Article En | MEDLINE | ID: mdl-36817086

Emerging evidence has revealed the significant roles of nicotinamide n-methyltransferase (NNMT) in cancer initiation, development, and progression; however, a pan-cancer analysis of NNMT has not been conducted. In this study, we first thoroughly investigated the expression and prognostic significance of NNMT and the relationship between NNMT and the tumor microenvironment using bioinformatic analysis. NNMT was significantly increased and associated with poor prognosis in many common cancers. NNMT expression correlated with the infiltration levels of cancer-associated fibroblasts and macrophages in pan-cancer. Function enrichment analysis discovered that NNMT related to cancer-promoting and immune pathways in various common cancers, such as colon adenocarcinoma, head and neck squamous cell carcinoma, ovarian serous cystadenocarcinoma, and stomach adenocarcinoma. NNMT expression was positively correlated with tumor-associated macrophages (TAMs), especially M2-like TAMs. The results suggest that NNMT might be a new biomarker for immune infiltration and poor prognosis in cancers, providing new direction on therapeutics of cancers.


Adenocarcinoma , Colonic Neoplasms , Head and Neck Neoplasms , Humans , Prognosis , Tumor Microenvironment , Biomarkers, Tumor/metabolism , Nicotinamide N-Methyltransferase/metabolism
8.
Gut Liver ; 17(6): 874-883, 2023 Nov 15.
Article En | MEDLINE | ID: mdl-36700302

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers. The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions: We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.


Gastrointestinal Stromal Tumors , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/diagnostic imaging , Artificial Intelligence , Endosonography , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Predictive Value of Tests
9.
Rapid Commun Mass Spectrom ; 36(18): e9355, 2022 Sep 30.
Article En | MEDLINE | ID: mdl-35840340

BACKGROUND: Gastroesophageal junction adenocarcinoma (GEJA) is a malignant tumor located at the junction of the esophagus and stomach, the incidence of which is increasing year by year, while screening for early biomarkers is limited. Tandem mass tagging (TMT) coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) has been used to screen for differential proteins in various cancers. METHODS: Differential proteins in GEJA and precancerous lesions were screened using TMT-LC/MS/MS, and then proteins that met expectations were selected for trend clustering analysis, combined with GO and KEGG analysis for functional annotation of differential proteins in GEJA. Then, parallel reaction monitoring and immunohistochemistry techniques were used to validate the accuracy of the proteomics data. RESULTS: Our group screened the differential proteins during GEJA progression using proteomics technology, analyzed the expression trends and functional regions involved in the differential proteins during carcinogenesis, and validated the accuracy of the experimental results. CONCLUSIONS: The screening of differential proteins in GEJA carcinogenesis based on TMT-LC/MS/MS technology provides detailed information for the elucidation of GEJA progression process, pathogenesis, early screening and screening of candidate markers.


Adenocarcinoma , Tandem Mass Spectrometry , Adenocarcinoma/diagnosis , Biomarkers/metabolism , Carcinogenesis , Chromatography, Liquid/methods , Esophageal Neoplasms , Esophagogastric Junction/metabolism , Humans , Tandem Mass Spectrometry/methods
10.
BMC Surg ; 22(1): 248, 2022 Jun 27.
Article En | MEDLINE | ID: mdl-35761304

BACKGROUND: The aim of this study is to evaluate and compare the safety and efficacy of endoscopic mucosal resection with a cap (EMR-c) with those of endoscopic submucosal dissection (ESD) for rectal neuroendocrine tumors (R-NETs) ≤ 15 mm in diameter, and to analyze the risk factors of incomplete resection. METHODS: A total of 122 patients who underwent EMR-c or ESD for R-NETs at the Fourth Hospital of Hebei Medical University between February 2007 and December 2020 were invovled in this study. The clinical outcomes of two groups were compared and evaluated. RESULTS: A total of 122 patients with 128 R-NETs underwent endoscopic resection (EMR-c, 80; ESD, 48). In terms of duration of operation, EMR-c was significantly shorter than ESD (p < 0.001). Univariate analysis and multivariate analysis suggested that tumor diameter ≥ 8 mm was an independent risk factor for incomplete resection in patients with R-NETs in this study. CONCLUSIONS: Both EMR-c and ESD were safe and effective treatments for R-NETs ≤ 15 mm in diameter. In addition, tumor diameter ≥ 8 mm was an independent risk factor for incomplete resection.


Endoscopic Mucosal Resection , Neuroendocrine Tumors , Rectal Neoplasms , Humans , Intestinal Mucosa/pathology , Intestinal Mucosa/surgery , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/surgery , Rectal Neoplasms/pathology , Retrospective Studies , Treatment Outcome
11.
Int J Colorectal Dis ; 37(2): 421-428, 2022 Feb.
Article En | MEDLINE | ID: mdl-34997303

PURPOSE: The detection rate of colorectal neuroendocrine tumours (CR-NETs) is increasing, but their treatment is still controversial. Lymph node metastasis is an important reference index for the selection of treatment. The aim of our study was to investigate the factors associated with lymph node metastasis and prognosis of CR-NETs. METHODS: The case characteristics of patients with colorectal neuroendocrine tumours from January 2011 to December 2020 were retrospectively analysed, including age, gender, tumour size, tumour location, lymph node metastasis, pathological grade and follow-up. RESULTS: A total of 195 cases of CR-NETs were included in this study. When 15 mm was used as the cut-off value, the sensitivity, specificity and area under the curve (AUC) of lymph node metastases were 95.9%, 95.2% and 0.986, respectively. Multivariate analysis suggested that tumour size ≥ 15 mm (OR: 30.517, 95% CI: 1.250 ~ 744.996, p = 0.036) and lymphovascular invasion (OR: 42.796, 95% CI: 2.882 ~ 635.571, p = 0.006) were independent risk factors for lymph node metastasis. Age ≥ 56 (HR: 7.434, 95% CI: 1.334 ~ 41.443, p = 0.022) and distant metastasis (HR: 24.487, 95% CI: 5.357 ~ 111.940, p < 0.001) were independent prognostic factors in multivariable analyses. CONCLUSIONS: When the size of a CR-NET is ≥ 15 mm, the risk of lymph node metastasis is higher, and it is recommended to choose the surgical method carefully. Tumour size and lymphovascular invasion were independent risk factors for lymph node metastasis. Age ≥ 56 and distant metastasis were independent prognostic factors.


Colorectal Neoplasms , Neuroendocrine Tumors , Colorectal Neoplasms/pathology , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Neoplasm Staging , Neuroendocrine Tumors/pathology , Prognosis , Retrospective Studies , Risk Factors
12.
World J Clin Cases ; 9(11): 2562-2568, 2021 Apr 16.
Article En | MEDLINE | ID: mdl-33889621

BACKGROUND: Primary esophageal small cell carcinoma (PESCC) is a highly aggressive malignancy, and its detailed clinical behaviors have remained virtually unknown. Because of the rapid tumor progression, the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice. Currently, only a handful of PESCC cases have been reported. CASE SUMMARY: Case 1: A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy. Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa. As the patient refused to undergo endoscopic resection, neoplasia was detected by endoscopy 1 year later. Case 2: A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital. About 2 wk later, we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa; the submucosal was thinner than normal but still continuous; mucosal hyperemia and erosion were found on the surface of the tumor. Endoscopic submucosal dissection (ESD) was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer. CONCLUSION: Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography. It is easily misdiagnosed as submucosal masses. Endoscopic manifestations should be identified and pathological biopsies should be employed. ESD may be performed to provide an opportunity for early treatment of PESCC.

13.
Ann Clin Lab Sci ; 48(3): 333-337, 2018 May.
Article En | MEDLINE | ID: mdl-29970437

Accumulation of single-nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with cancer risk and disease outcome. We evaluated the predictive value of these SNPs for GEP-NEN outcome. Three SNP sites of nucleotides 16257C/A, 150C/T and 151C/Tdel were identified for statistically significant prediction of postoperative survival in GEP-NEN by univariate analysis with log-rank test. In addition, the minor haplotype of nucleotides 16257A in the hypervariable segment 1(HV1) region of the D-loop was identified for their association with lower survival rate of GEP-NEN (relative risk, 3.390; 95% CI, 1.071~10.729; p=0.038) by multivariate analysis with COX hazards model. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups with a high risk of GEP-NEN outcome.


DNA, Mitochondrial/genetics , Intestinal Neoplasms/genetics , Intestinal Neoplasms/mortality , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/mortality , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/mortality , Polymorphism, Single Nucleotide , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Female , Follow-Up Studies , Humans , Intestinal Neoplasms/pathology , Male , Middle Aged , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , Prognosis , Stomach Neoplasms/pathology , Survival Rate
14.
Oncol Lett ; 13(4): 2391-2396, 2017 Apr.
Article En | MEDLINE | ID: mdl-28454409

The aim of the present study was to investigate the expression and clinical significance of oncofetal protein insulin-like growth factor (IGF) II mRNA-binding protein 3 (IMP3) in the differentiation of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). A total of 162 patients who were diagnosed with GEP-NEN, and who underwent surgical or endoscopic resection from January 2006 to March 2013, were enrolled in the study, including 85 cases of grade (G)1 neuroendocrine tumors, 40 cases of G2 neuroendocrine tumors, 28 cases of G3 neuroendocrine carcinomas and 9 cases of mixed stage adenoneuroendocrine carcinomas. The clinical and pathological data were recorded for analysis. The expression of IMP3, cluster of differentiation (CD)44, IGF1 receptor (IGF1R) and matrix metalloproteinase (MMP)2 was determined by immunohistochemistry. SPSS 13.0 software was used for data processing and analyses, and P<0.05 was used to determine significance. Oncofetal protein IMP3 exhibited a high expression rate (74.69%) in GEP-NEN. IMP3-positive cases demonstrated significantly decreased overall and disease-free survival times, as compared with IMP3-negative cases (P=0.012). Overexpression of IMP3 was correlated with tumor grade, clinical stage, tumor size and poor prognosis (all P<0.05). Therefore, patients with overexpressed IMP3 had a poorer prognosis (P<0.01); COX regression analysis revealed that the overexpression of IMP3, the tumor grade, tumor size and metastasis of GEP-NEN were each associated with the clinical outcomes. The results also indicated that the expression rates of CD44, IGF1R and MMP2 in GEP-NEN were 19.75, 53.7 and 55.56%, respectively. While it was negatively associated with the expression of CD44 (r=-0.131; P=0.096), the expression of IMP3 was positively correlated with the expression of IGF1R and MMP2 (r=0.288, P<0.01; r=0.208, P=0.008). In addition, the expression levels of IGF1R and MMP2 were positively associated (r=0.687; P<0.01). In conclusion, high IMP3 expression levels were determined to be associated with a high disease stage in patients with GEP-NEN, thus it may serve as a predictor for metastasis and poor clinical outcomes in GEP-NEN.

15.
Int J Clin Exp Pathol ; 10(10): 10269-10275, 2017.
Article En | MEDLINE | ID: mdl-31966361

This study aimed to investigate the role of insulin-like growth factor II mRNA binding protein 3 (IMP3) in neuroendocrine tumor (NET). Mouse NET STC-1 cell line was chosen as the experimental model and three IMP3-targeting siRNAs and a non-specific scramble siRNA were transfected into STC-1 cells. The efficiency of IMP3 siRNA to knockdown IMP3 was evaluated by immunocytochemical staining. Cell proliferation was detected by MTT assay. Cell migration and invasion was analyzed with Transwell chamber assay. Protein expression was detected by Western blot analysis. We found that IMP3 silencing inhibited the proliferation of STC-1 cells potentially by downregulating the expression of cell proliferation associated proteins EGFR and Ki67. Furthermore, IMP3 silencing inhibited the migration and invasion of STC-1 cells potentially by downregulating the expression of metastasis associated proteins IGF1R, MMP2 and MMP9. In conclusion, this study provides the first evidence that IMP3 plays an oncogenic role in Net and is a promising therapeutic target for NET.

16.
J Clin Lab Anal ; 31(5)2017 Sep.
Article En | MEDLINE | ID: mdl-27704598

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors that arise from the diffuse neuroendocrine system, and the biggest advances in molecular biology have helped in understanding these biological diversity of tumors over the past decades. It is important to determine the carcinogenesis of GEP-NEN from the perspective of genetic backgrounds. METHODS: Mitochondrial DNA (mtDNA) of peripheral blood from 66 GEP-NEN patients and from 75 healthy controls without history of any cancer were examined for single nucleotide polymorphisms (SNPs) and mutations in the displacement loop (D-loop) region. RESULTS: Single nucleotide polymorphisms were detected in 148 sites within the 982 bp mitochondria D-loop region from blood samples of healthy controls and GEP-NEN patients. SNPs with a rare allele frequency >5% in either controls or GEP-NEN patients were used for cancer risk analysis; a total of 23 SNPs were selected. When individual SNPs of GEP-NEN patients compared with healthy controls were analyzed, a statistically significant increase in the SNP frequency was observed for 73G, 150T, 151T, 492C, 16257A, 16261T, and 16399G in GEP-NEN patients (P<.05). It was also observed that the SNP frequency for 489C and 16519C significantly decreased in GEP-NEN patients compared with controls (P<.05). CONCLUSION: In summary, SNPs in the mutations of the mitochondrial D-loop may be valuable markers for GEP-NEN risk evaluation. Analysis of the genetic polymorphisms in the D-loop may be useful for diagnosis of high-risk individuals.


DNA, Mitochondrial/genetics , Intestinal Neoplasms/epidemiology , Intestinal Neoplasms/genetics , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/genetics , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , Stomach Neoplasms/epidemiology , Stomach Neoplasms/genetics , Case-Control Studies , Female , Humans , Male , Middle Aged
17.
Mol Biol Rep ; 37(8): 3983-9, 2010 Dec.
Article En | MEDLINE | ID: mdl-20300863

Polymorphisms in cytokine genes may contribute to increased susceptibility to different cancers. The aim of this paper is to investigate the association of IL-8-251A/T polymorphism and Helicobacter pylori (H. pylori) infection with the risk of developing gastric cardiac adenocarcinoma (GCA) in the south of Taihang Mountain, a high-incidence area of esophageal cancer in China. The IL-8-251 A/T polymorphism was genotyped in 519 cases of GCA and 504 healthy controls. The H. pylori infection in GCA patients and controls was detected by rapid urease test (RUT), histopathology or (14)C-urea breath test ((14)C-UBT). The results showed that family history of upper gastrointestinal cancer (UGIC) and H. pylori infection significantly increased the risk of developing GCA. The overall genotype and allelotype distributions of IL-8 promoter SNPs in GCA patients were significantly different from those in healthy controls. Compared with TT genotype, AA genotype significantly elevated the risk of developing GCA. The stratification analysis revealed that, compared with the TT genotype, the AA genotype significantly elevated the risk of developing GCA in both positive family history of UGIC and H. pylori infection subgroups. This study provides evidence to support a relationship of increased susceptibility to GCA in individuals of the south Taihang Mountain region with IL-8 251 AA genotype, especially for those individuals who have family history of UGIC or H. pylori infection.


Adenocarcinoma/genetics , Genetic Predisposition to Disease , Helicobacter Infections/complications , Interleukin-8/genetics , Polymorphism, Single Nucleotide/genetics , Stomach Neoplasms/epidemiology , Stomach Neoplasms/genetics , Adenocarcinoma/complications , Adenocarcinoma/epidemiology , Aged , Base Sequence , China/epidemiology , Demography , Female , Helicobacter Infections/genetics , Helicobacter pylori/physiology , Humans , Incidence , Male , Middle Aged , Molecular Sequence Data , Polymerase Chain Reaction , Precancerous Conditions/epidemiology , Precancerous Conditions/genetics , Risk Factors , Sequence Analysis, DNA , Stomach Neoplasms/complications
18.
Mol Biol Rep ; 37(1): 219-25, 2010 Jan.
Article En | MEDLINE | ID: mdl-19626461

DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29-0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37-1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age < 55 (OR = 0.31, 95% CI = 0.12-0.84) and males (OR = 0.35, 95% CI = 0.17-0.71). Meanwhile, combined G/T + G/G genotypes were found to have a lower risk in non-drinkers to develop both colorectal adenomatous polyps and adenocarcinoma (OR = 0.54, 95% CI = 0.31-0.96 and OR = 0.48, 95% CI = 0.27-0.84, respectively). This study also showed a distinct difference in the distribution of DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.


Adenocarcinoma/genetics , Adenomatous Polyps/genetics , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Adenocarcinoma/enzymology , Adenomatous Polyps/enzymology , Case-Control Studies , Demography , Ethnicity/genetics , Female , Gene Frequency/genetics , Humans , Male , Middle Aged , Polymerase Chain Reaction , DNA Methyltransferase 3B
19.
Zhonghua Zhong Liu Za Zhi ; 30(11): 853-7, 2008 Nov.
Article Zh | MEDLINE | ID: mdl-19173832

OBJECTIVE: To evaluate the long-term effect and clinical value of endoscopic mucosal resection (EMR) with transparent cap for dysplasia and early-stage cancer of the esophagus and gastric cardia. METHODS: From September 1996 to June 2007, 154 lesions in the esophagus or gastric cardia of 147 patients were treated using EMR with transparent cap. Among the lesions, there were 69 early-stage squamous-cell carcinomas in 64 patients and 47 squamous cell precancerous lesions of the esophagus in 45 patients, with an average lesion size of (14.8 +/- 6.1) mm (range, 3-40 mm), furthermore, there were 23 early-stage adenocarcinomas in 23 patients and 15 precancerous lesions in the gastric cardia in 15 patients, with an average lesion size of (8.2 +/- 4.3) mm (rang, 5-25 mm). All lesions were finally confirmed histopathologically. RESULTS: Of the 154 lesions, 139 (90.3%) were resected completely through EMR procedure. A close relationship between the complete resection rate and the lesion size was observed. The bigger the lesion size, the lower the complete resection rate. Endoscopic follow-up was carried out in 7 patients for more than 10 years, in 43 for 5 - 10 years, in 31 for 3 - 5 years and in 66 for less than 3 years. Of 11 dead patients during following-up, 10 died of other diseases, only 1 of recurrence. The 5-year survival rate was 96.2% for early-stage esophageal cancer, and 100% for early cancer of the gastric cardia. Perioperative complications included oozing bleeding in 5 patients (3.4%) and stricture in 1 (0.7%), no perforation occurred in this series. CONCLUSION: Endoscopic mucosal resection is suitable to treat precancerous lesions or early-stage esophageal cancers without invasion into submucosa. Compared with conventional resection through open thoracotomy, similar long-term survival and curative effect can be achieved by this EMR treatment, preserving a good quality of life.


Cardia , Esophageal Neoplasms/surgery , Esophagoscopy/methods , Precancerous Conditions/surgery , Stomach Neoplasms/surgery , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Gastric Mucosa/pathology , Gastric Mucosa/surgery , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Precancerous Conditions/pathology , Stomach Neoplasms/pathology , Survival Rate
20.
Zhonghua Zhong Liu Za Zhi ; 29(6): 441-3, 2007 Jun.
Article Zh | MEDLINE | ID: mdl-17974279

OBJECTIVE: To analyze the alterations of serum proteomic pattern in esophageal squamous cell carcinoma (ESCC) by SELDI-TOF-MS, to establish a diagnostic model of ESCC screening in high incidence area and investigate its clinical value. METHODS: SELDI-TOF-MS and CM10 proteinChip were used to detect the serum proteomic patterns of 36 cases of ESCC and 38 healthy control subjects in high incidence area. The data were analyzed and a diagnostic model was established by using support vector machine (SVM). The diagnostic model was evaluated by leave-one-out cross validation. RESULTS: At the molecular weight range of 2000 to 20,000, 31 protein peaks were significantly different between ESCC and controls (P < 0.01). A diagnostic model consisting of 4 protein peaks could do the best in diagnosis of ESCC and controls. The accuracy was 85.1%, sensitivity was 86.1%, specificity was 84.2%, and positive value was 83.8%. CONCLUSION: The diagnostic model formed by 4 protein peaks, established in this study, can well distinguish ESCC from healthy subjects. It provides a new approach for ESCC screening in high incidence area.


Blood Proteins/analysis , Carcinoma, Squamous Cell/diagnosis , Esophageal Neoplasms/diagnosis , Proteomics/methods , Adult , Aged , Blood Proteins/chemistry , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/epidemiology , China/epidemiology , Esophageal Neoplasms/blood , Esophageal Neoplasms/epidemiology , Humans , Incidence , Mass Screening , Middle Aged , Peptide Mapping , Protein Array Analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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