Progressive Gastric Cancer Research Articles

Application of computed tomography body composition in patients with locally progressive gastric cancer undergoing radical surgery combined with prophylactic hyperthermic intraperitoneal chemotherapy.

Radical resection combined with prophylactic hyperthermic intraperitoneal chemotherapy (p-HIPEC) is a promising treatment for locally advanced gastric cancer (LAGC), though factors influencing its long-term benefits remain unclear. This study aimed to assess the impact of computed tomography (CT)-based body composition parameters on survival in patients undergoing this combination treatment, exploring nutritional factors affecting long-term survival and developing a prognostic model. We retrospectively analyzed clinical and CT data from 230 patients with LAGC who underwent radical resection with p-HIPEC between January 2017 and December 2020. Cox regression and Kaplan-Meier analysis were used to identify independent risk factors, and nomograms were constructed based on significant predictors. The models' accuracy was evaluated using receiver operating characteristic (ROC) curves and calibration plots. Of the 230 patients, the 3-year survival rate was 56.1%, with a median overall survival of 49.7 months. Multivariate analysis identified sarcopenia (hazard ratio [HR], 3.078; p < 0.001), low subcutaneous adipose tissue index (HR, 1.739; p = 0.002), high visceral-to-subcutaneous adipose tissue ratio (HR, 1.746; p = 0.002), pT stage (p < 0.001), pN stage (N3: p = 0.004; N2: p = 0.049), and vascular invasion (p < 0.001) as independent risk factors for poor survival. Nomograms incorporating body composition and tumor features predicted 1-, 3-, and 5-year overall survival with high accuracy (AUC >0.7). Body composition and tumor characteristics are independent predictors of overall survival in LAGC patients. Nomograms integrating these factors provide reliable prognostic predictions.

Identification of FGG as a Biomarker in Early Gastric Cancer via Tissue Proteomics and Clinical Verification.

Early and accurate diagnosis of gastric cancer (GC) is essential for reducing mortality and improving patient well-being. However, methods for the early diagnosis of GC are still lacking. In this study, by isobaric tagging for relative and absolute quantitation (iTRAQ), we identified 336 proteins that overlapped among the upregulated differentially expressed proteins (DEPs) in early gastric cancer (EGC) versus progressive gastric cancer (PGC), upregulated DEPs in EGC versus nongastric cancer (NGC), and nonsignificant proteins in EGC versus NGC. These DEPs were involved primarily in the neutrophil-related immune response. Network analysis of proteins and pathways revealed that fibrinogen α (FGA), β (FGB), and γ (FGG) are candidates for distinguishing EGC. Furthermore, parallel reaction monitoring (PRM), immunohistochemistry (IHC), and Western blot (WB) assays of clinical samples confirmed that, compared with that in PGC and NGC, only FGG was uniquely and significantly upregulated in the gastric mucosa of EGC. Our results demonstrated that FGG in the gastric mucosa could be a novel biomarker to diagnose EGC patients via endoscopy.

18F-FDG PET/CT metabolism multi-parameter prediction of chemotherapy efficacy in locally progressive gastric cancer

PurposeThis study aimed to use an 18F-FDG PET/CT multiparametric quantitative analysis to determine the efficacy of neoadjuvant chemotherapy in patients with locally progressive gastric cancer.Materials and methodsWe conducted a retrospective analysis of 34 patients with pathologically identified gastric cancer who received neoadjuvant chemotherapy and surgery. Chemotherapy regimens were followed and 18F-FDG PET/CT was conducted. We ascertained multiparamaters of the target lesions pre- and post-treatment and determined the ideal cutoff values for the percentage change in biomarkers. Independent factors were evaluated using binary logistic regression. A response classification system was used to explore the association between metabolic and anatomical responses and the degree of pathological remission.ResultsBinary logistic regression analysis showed that Lauren bowel type and change in total lesion glycolysis >45.2% were risk predictors for the efficacy of neoadjuvant chemotherapy; total lesion glycolysis demonstrated the best predictive efficacy. The categorical variable system of the two-module response (metabolic and anatomical response) group had a higher predictive accuracy than that of the single-module response (metabolic or anatomical response) group.ConclusionsUsing 18F-FDG PET/CT multiparametric quantitative analysis, Lauren bowel type and change in total lesion glycolysis >45.2% were independent predictors of the efficacy of neoadjuvant chemotherapy in patients with gastric adenocarcinoma. Additionally, the dual-module assessment demonstrated high predictive efficacy.

Effects of Yipi Huayu decoction on tumor markers, immune function, and adverse reactions during chemotherapy in gastric cancer patients: a retrospective propensity score-matched study.

To analyze the effects of Yianpi Huayu Decoction on tumor markers, immune function and adverse reactions during chemotherapy in patients with gastric cancer. The clinical data of 154 patients with progressive gastric cancer who attended Baoji Maternal and Child Health Hospital (Daijiawan Branch) from January 2020 to March 2022 were retrospectively analyzed. The patients were divided into an observation group (61 cases) and a control group (93 cases) according to the treatment method and were matched using propensity score matching (PSM). The control group was given SOX neoadjuvant chemotherapy regimen (oxaliplatin + tiglio), and the observation group was given spleen-strengthening and blood-stasis-reducing tonics as adjuvant treatment on the basis of the treatment given to the control group. Clinical efficacy in the two groups was observed, as well as Carbohydrate Antigen 19-9 (CA19-9), Carbohydrate Antigen 72-4 (CA72-4), and Carcinoembryonic Antigen (CEA) levels, immune function (IgA, IgM, and IgG), Karnofsky Performance Scale (KPS), and occurrence of adverse reactions. After matching, there was no significant difference in the total clinical efficiency between the two groups (P > 0.05). After matching, there were no differences in CA19-9, CA72-4, and CEA levels between the observation group and the control group before or after treatment (P > 0.05). After matching, the IgA, IgM, and IgG levels in the observation group were significantly better than those in the control group after treatment (P < 0.05). The incidence of leukopenia (P = 0.011) and diarrhea (P = 0.011) during treatment was higher in the control group than in the observation group after matching. The KPS score of the observation group was higher than that of the control group after matching (P < 0.05). After matching, Cox regression analysis found that the treatment regimen (P < 0.001, HR = 2.527), TNM staging (P = 0.001, HR = 0.471), local recurrence (P = 0.001, HR = 2.147), and pretreatment CEA (P = 0.011, HR = 1.131) were independent prognostic factors affecting patients' 2-year survival. While the spleen-enhancing and blood-stasis-removing herbal formula combined with the SOX chemotherapy regimen did not improve therapeutic outcomes in gastric cancer patients, it did enhance immune function, reduce adverse reactions, and improve quality of life.

Predictive and prognostic value of combined detection of sTim-3, PG and PD-L1 in immune checkpoint inhibitor therapy for advanced gastric cancer.

To investigate the value of combined detection of T-cell immunoglobulin mucin molecule 3 (sTim-3), pepsinogen (PG) and programmed death receptor 1 (PD-L1) in evaluating treatment efficacy and predicting the prognosis of immunosuppressant therapy in advanced gastric cancer. A retrospective study was conducted on the data of 90 patients with advanced gastric cancer who were treated at the First Affiliated Hospital of Changsha Medical University from January 2019 to February 2021. Patients were divided into effective and ineffective groups based on treatment response. Logistic regression was used to identify the factors affecting the efficacy of immune checkpoint inhibitors in treating progressive gastric cancer. ROC curves were drawn to assess the predictive value of serum sTim-3, PG, and PD-L1 alone or in combination. Serum levels of sTim-3, PG, PD-L1 were compared between the survival and death groups, and univariate and Cox proportional risk regression analyses were conducted to identify factors affecting prognosis of patients with progressive gastric cancer. Survival curves were plotted using the Kaplan-Meier method, and ROC curves were used to assess the prognostic value of combined and individual testing of sTim-3, PG, and PD-L1. No statistically significant difference were observed between the effective and ineffective groups in terms of gender, age, body mass index, smoking history, alcohol consumption history, KPS score, tumor site, presence of ascites, or use of other therapies (all P>0.05). The levels of sTim-3, PG II, and PD-L1 were higher in the ineffective group than those in the effective group, while PG I was lower than that in the effective group (all P<0.05). Logistic regression analysis showed that sTim-3 (OR=2.408), PG I (OR=1.779) and PD-L1 (OR=1.844) were independent risk factors for treatment efficacy of immune checkpoint inhibitors in advanced gastric cancer (all P<0.05). The AUC value of combined detection of serum sTim-3, PG I and PD-L1 for treatment efficacy was higher than their individual detection (P<0.05). The serum levels of sTim-3 and PD-L1 in the death group were higher than those in the survival group, while PG I was lower than that in the survival group. The levels of sTim-3 (HR=2.686), PG I (HR=2.782) and PD-L1 (HR=2.018) were independent prognostic factors in patients with advanced gastric cancer. The AUC of the combined detection of sTim-3, PG I and PD-L1 in predicting the prognosis of patients with advanced gastric cancer was significantly higher than their individual detection (all P<0.05). Log-rank test showed that the 3-year survival rates of patients with high sTim-3 and PD-L1 levels were significantly higher than those with low levels (all P<0.05). sTim-3, PG and PD-L1 have significant clinical value in predicting treatment efficacy and prognosis of advanced gastric cancer patients undergoing immunosuppressive therapy.

Imaging advances in efficacy assessment of gastric cancer neoadjuvant chemotherapy.

Effective neoadjuvant chemotherapy (NAC) can improve the survival of patients with locally progressive gastric cancer, but chemotherapeutics do not always exhibit good efficacy in all patients. Therefore, accurate preoperative evaluation of the effect of neoadjuvant therapy and the appropriate selection of surgery time to minimize toxicity and complications while prolonging patient survival are key issues that need to be addressed. This paper reviews the role of three imaging methods, morphological, functional, radiomics, and artificial intelligence (AI)-based imaging, in evaluating NAC pathological reactions for gastric cancer. In addition, the advantages and disadvantages of each method and the future application prospects are discussed.

Identification of PRTN3 as a novel biomarker for the diagnosis of early gastric cance

Gastric cancer (GC) remains one of the most common types of cancer worldwide and has a high mortality rate. However, tools for the early detection of gastric cancer are still lacking. Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assays were conducted to identify and quantify the differentially expressed proteins (DEPs) in the gastric mucosal tissues of GC patients at different stages. Bioinformatics analysis was used to identify the pathways enriched among the DEPs and candidate marker proteins. The expression levels and distribution of candidate proteins were confirmed by parallel reaction monitoring (PRM) analysis. In this study, by using the iTRAQ quantitative proteomic strategy, we identified 727 and 502 DEPs that were upregulated in EGC vs. PGC and EGC vs. NGC, respectively. These DEPs were mainly involved in the innate immune response and RNA binding. PRTN3 was identified as a marker of early gastric cancer by Gene Ontology enrichment analysis. Furthermore, the PRM assay confirmed the significant overexpression of PRTN3 in EGC gastric mucosa compared to PGC and NGC mucosa. Our data demonstrated that PRTN3 in the gastric mucosa could be used as a novel biomarker to identify patients with early gastric cancer via endoscopy. SignificanceGastric cancer remains one of the most common types of cancer worldwide and has a high mortality rate. Patients with progressive gastric cancer and gastroesophageal junction cancer have a poor prognosis, with a 5-year relative survival rate of 6%. Therefore, early detection and diagnosis of gastric cancer is a key step toward improving the survival rate.The present study identified PRTN3 as a marker of early gastric cancer by an iTRAQ quantitative proteomic strategy. The PRM assay confirmed the significant overexpression of PRTN3 in EGC gastric mucosa compared to PGC and NGC mucosa. This study discovered that PRTN3 in the gastric mucosa could be used as a novel biomarker to identify patients with early gastric cancer via endoscopy.

Clinical Significance of Fibrinogen and Platelet to Pre-Albumin Ratio in Predicting the Prognosis of Advanced Gastric Cancer.

The aim of this study was to investigate the clinical significance of Fibrinogen and Platelet to Pre-albumin Ratio(FPAR) in predicting the prognosis of patients with advanced gastric cancer(AGC) and to construct a predictive model. We collected clinical data from 489 postoperative patients with AGC. FPAR was divided into high and low groups according to the receiver operating characteristic (ROC) curve. The value of FPAR in predicting the prognosis of progressive gastric cancer was analysed using univariate and multivariable Cox regression analysis and its relationship with clinicopathological features. Finally, the Overall Survival(OS) and recurrence-free survival(RFS) prediction models were constructed and validated using FPAR. Univariate and multifactorial cox regression analysis showed that grade (P<0.001), TNM-stage (P<0.001), chemotherapy (P<0.001), and FPAR (OR=3.054,95% CI:2.088-4.467, P<0.001) were independent risk factors for OS; grade (P=0.021), N-stage (P=0.024), TNM-stage (P=0.033), and FPAR (OR=2.215,95% CI:1.634-3.003, P<0.001) were independent risk factors for RFS. Subgroup analysis showed that the FPAR-low group had higher OS and RFS than the FPAR-high group, regardless of the patient's TNM stage (p<0.05). However, OS was instead higher in the the stage III-FPAR-low group than in the the stage II-FPAR-high group (p<0.05), while RFS was not significantly different. Predictive models incorporating FPAR had better predictive performance than those without FPAR, showing wide range of net benefit and AUC. After correction, the 2-year AUC, 3-year AUC and C-index of the OS model were 0.737, 0.756, and 0.746; the 2-year AUC, 3-year AUC, and C-index of the RFS model were 0.738, 0.758, and 0.711. FPAR levels were associated with prognosis in patients with AGC and could independently predict RFS and OS.

ATXN2-Mediated PI3K/AKT Activation Confers Gastric Cancer Chemoresistance and Attenuates CD8+ T Cell Cytotoxicity.

As one of the primary therapeutic choices, chemotherapy is widely adopted for progressive gastric cancer (GC), but the development of chemoresistance has limited chemotherapy efficacy and partly contributes to poor prognosis. Immunotherapy is increasingly being applied in the clinical treatment of GC and is also benefitting patients. To ascertain whether ATXN2 affects chemotherapy efficacy in GC cells and its role in GC immune escape, we performed high-throughput sequencing to clarify genes differentially expressed between 5-FU-resistant and 5-FU-sensitive GC cells and then conducted qRT–PCR to assess ATXN2 expression in GC tissues. Furthermore, the influence of ATXN2 on resistance was studied in vitro and in vivo, ATXN2 and other protein expression levels were detected using Western blotting and immunohistochemistry (IHC), and the direct association of SP1 and ATXN2 was confirmed through luciferase reporter gene analysis. We found elevated ATXN2 in GC tumors and a negative correlation between ATXN2 levels and the prognosis of GC. Furthermore, by activating the PI3K/AKT pathway, ATXN2 was found to promote chemoresistance in GC, facilitating BCL2L1 expression. In GC cells, ATXN2 further stimulated PD-L1 expression and provided better immunotherapy efficacy. Finally, we demonstrated that SP1 transcriptionally regulated the expression of ATXN2 and prompted GC chemoresistance and immune escape. In conclusion, our study reveals the important roles of the SP1/ATXN2/PI3K-AKT/BCL2L1 signalling pathway in GC chemoresistance and of the SP1/ATXN2/PI3K-AKT/PD-L1 signalling pathway in GC immunotherapy. Our findings provide new theories and experimental references for overcoming chemotherapy resistance in GC and enhancing the efficacy of immunotherapy for GC.

Clinical Efficacy of Acupuncture on Neoadjuvant Chemotherapy with Capecitabine plus Paclitaxel and Radiotherapy in Progressive Gastric Cancer.

Objective To assess the clinical efficacy of acupuncture on neoadjuvant chemotherapy with capecitabine plus paclitaxel and radiotherapy in progressive gastric cancer. Methods In this randomized, double-blind, controlled clinical trial, 70 patients with advanced gastric cancer receiving radio-chemotherapy between May 2018 and June 2020 were assessed for eligibility in our institution and recruited. They were assigned via the random number table method at a ratio of 1 : 1 to receive either neoadjuvant chemotherapy with capecitabine plus paclitaxel and radiotherapy (control group) or acupuncture on neoadjuvant chemotherapy with capecitabine plus paclitaxel and radiotherapy (intervention group). The outcome measures included symptom mitigation, quality of life, and traditional Chinese medicine (TCM) symptom scores. Results The two groups showed similar results in abdominal circumference, intraabdominal pressure, and bowel sounds before treatment (P > 0.05). Acupuncture plus conventional treatment was associated with better mitigation on intraabdominal pressure (11.08 ± 1.37 vs. 12.17 ± 2.68) and bowel sounds (4 [3, 4] vs. 3 [3, 4]) versus conventional treatment alone (P < 0.05). No statistically significant difference in TCM symptom scores was observed between the two groups before treatment (P > 0.05). Acupuncture plus conventional treatment resulted in a lower TCM symptom score (24.63 ± 4.56 points) versus conventional treatment (31.17 ± 4.91 points) (P < 0.05). The eligible patients given acupuncture showed significantly higher scores of physical function, role function, emotional function, cognitive function, and social function (81.52 ± 5.37, 88.17 ± 5.17, 85.15 ± 6.71, 78.45 ± 5.85, and 80.98 ± 7.14) versus those without acupuncture (52.98 ± 8.23, 69.87 ± 5.54, 68.24 ± 9.22, 61.34 ± 6.27, and 64.79 ± 6.89) (P < 0.05). Conclusion Acupuncture is effective in the recovery of acute toxicity after radio-chemotherapy for patients with advanced gastric cancer, which provides a certain reference for clinical treatment and is worthy of application and promotion.

Helicobacter pylori-Mediated Oxidative Stress and Gastric Diseases: A Review.

Gastric cancer is considered to be a type of gastrointestinal tumor and is mostly accompanied by Helicobacter pylori (HP) infection at the early stage. Hence, the long-term colonization of the gastric mucosa by HP as a causative factor for gastrointestinal diseases cannot be ignored. The virulence factors secreted by the bacterium activate the signaling pathway of oxidative stress and mediate chronic inflammatory response in the host cells. The virulence factors also thwart the antibacterial effect of neutrophils. Subsequently, DNA methylation is induced, which causes continuous cell proliferation and evolution toward low-grade-differentiated gastric cells. This process provides the pathological basis for the occurrence of progressive gastric cancer. Therefore, this review aims to summarize the oxidative stress response triggered by HP in the gastric mucosa and the subsequent signaling pathways. The findings are expected to help in the formulation of new targeted drugs for preventing the occurrence of early gastric cancer and its progression to middle and advanced cancer.

Observation of the effectiveness and safety of the combination of chemotherapy and radiotherapy after the radical resection of progressive gastric cancer

Observation of the effectiveness and safety of the combination of chemotherapy and radiotherapy after the radical resection of progressive gastric cancer

Long-term outcome after hand and forearm transplantation - a retrospective study.

SummaryBetween 2000 and 2014, five patients received bilateral hand (n = 3), bilateral forearm (n = 1), and unilateral hand (n = 1) transplants at the Innsbruck Medical University Hospital. We provide a comprehensive report of the long‐term results at 20 years. During the 6–20 years follow‐up, 43 rejection episodes were recorded in total. Of these, 27.9% were antibody‐related with serum donor‐specific alloantibodies (DSA) and skin‐infiltrating B‐cells. The cell phenotype in rejecting skin biopsies changed and C4d‐staining increased with time post‐transplantation. In the long‐term, a change in hand appearance was observed. The functional outcome was highly depending on the level of amputation. The number and severity of rejections did not correlate with hand function, but negatively impacted on the patients´ well‐being and quality of life. Patient satisfaction significantly correlated with upper limb function. One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer. The other four patients are currently rejection‐free with moderate levels of immunosuppression. Hand transplantation remains a therapeutic option for carefully selected patients. A stable immunologic situation with optimized and individually adopted immunosuppression favors good compliance and patient satisfaction and may prevent development of DSA.

Status and progress in the treatment for locally resectable progressive gastric cancer and metastatic gastric cancer.

For resectable gastric cancer, although radical surgery is still the main treatment, methods of operation and the curative effect of operation are still in the stage of exploration for metastatic gastric cancer. Radiotherapy, chemotherapy and molecular targeted therapy also play an important role in prolonging the survival period of patients with gastric cancer. Postoperative radiotherapy and chemotherapy can prolong the survival time, but for patients with locally advanced gastric cancer, the preoperative radiotherapy and chemotherapy can also further improve the survival period of patients compared with direct operation. In addition, with the development and using of molecular targeted drugs, such as antiangiogenic agents, immunosuppressive drugs and so on, the survival period of patients with gastric cancer has been further extended.

Prognostic value of CEA/CA72-4 immunohistochemistry in combination with cytology for detecting tumor cells in peritoneal lavage in gastric cancer.

Aim: To study the value and efficiency of CEA/CA72-4 immunohistochemistry in detecting free tumor cells from peritoneal lavage, in order to provide reliable lab information for subsequent intraperitoneal chemotherapy. Methods: A total of 112 progressive gastric cancer patients were enrolled from Oct. 2016 to Oct 2017, who were pathologically diagnosed as gastric cancer after surgery. Peritoneal lavage was respectively collected during operation. Cytology and CEA/CA72-4 immunohistochemistry of peritoneal lavage samples was performed. Overall survival and recurrence free survival was analyzed. Results: Cytology showed 16 positive cases (14.29%), CEA immunohistochemistry showed 29 positive cases (25.89%), CA72-4 immunohistochemistry showed 33 positive cases (29.46%). McNemar's test showed significant difference in positivity between cytology (CY+) and CEA/CA72-4 immunohistochemistry (IHC+). Kappa test showed consistency between immunohistochemistry of CEA and CA72-4 with cytology. Patients with CY+/IHC+ had the poorest overall survival (OS) as well as recurrence free survival (RFS), followed by those with CY+ or IHC+, while those with CY-/IHC- had higher OS and RFS. The differences of OS and RFS in IHC+ group were worse than that in IHC- group. Kaplan-Meier analysis showed that positive CEA/CA72-4 IHC revealed poorer prognosis than the negative cases. Conclusions: Due to the limitation of cytology, combination of cytology and immunohistochemistry appears to be more efficient for predicting prognosis of progressive gastric cancer.

Long non-coding RNA AFAP1-AS1 promotes proliferation and migration of gastric cancer by downregulating KLF2.

To clarify the function of actin filament associated protein 1-antisense RNA1 (AFAP1-AS1) to promote the proliferation and migration of gastric cancer (GC) cells by downregulating Krüppel-like factor 2 (KLF2). Expression level of AFAP1-AS1 in GC tissues and matched paracancerous tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Besides, its level in GC either with lymphatic metastasis or not, and those in different tumor stages were determined as well. Regulatory roles of AFAP1-AS1 in cellular behaviors of GC cells were evaluated by functional experiments. The ability of AFAP1-AS1 to recruit EZH2 was evaluated through chromatin immunoprecipitation (ChIP) assay. The expression level of KLF2 in GC cells influenced by AFAP1-AS1 and EZH2 was detected by Western blot. Finally, a series of rescue experiments were conducted to clarify the role of AFAP-AS1/KLF2 in GC cell performances. AFAP1-AS1 was upregulated in GC tissues, and its expression in lymph node metastasis and progressive gastric cancer tissues were much higher. Knockdown of AFAP1-AS1 reduced the viability, proliferative and migratory abilities, but induced apoptosis of GC cells. AFAP1-AS1 was verified to bind to EZH2. After knockdown of AFAP1-AS1, the ability of AFAP1-AS1 to recruit EZH2 was remarkably attenuated. Knockdown of AFAP1-AS1 or EZH2 upregulated KLF2 expression in GC cells. Notably, knockdown of KLF2 partially reversed the effect of AFAP1-AS1 on GC cell performances. LncRNA AFAP1-AS1 accelerates the proliferative and migratory abilities of GC cells by downregulating the expression of KLF2, thus promoting the progression of GC.

Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer

Abnormal activation of the hedgehog (Hh) signaling pathway has been found to be involved in the occurrence, invasion, and metastasis of cancers. Epithelial-mesenchymal transition (EMT) also plays an important role in the invasion and metastasis of cancers. However, the significance of the Hh signaling pathway and EMT in the invasion and metastasis of gastric cancer is still unclear. This study aimed to investigate the significance and prognostic value of the Hh signaling pathway and EMT in progressive gastric cancer. Immunohistochemistry was performed to detect the expression of the Hh-induced transcriptional factor Gli-1 and the EMT-related molecules Snail and E-cadherin in 121 patients with progressive gastric cancer. Histological type, depth of invasion, lymph node metastasis, and pTNM stage were also recorded. In progressive gastric cancer, Gli-1 expression increased markedly, and was closely associated with increased Snail expression and decreased E-cadherin expression. Diffuse type cancer, lymph node metastasis, and abnormal expression of E-cadherin were independent factors influencing the prognosis of patients with progressive gastric cancer. These findings suggest that abnormal activation of the Hh signaling pathway is closely related to the presence of EMT and is an important factor influencing the prognosis of patients with diffuse progressive gastric cancer.

Endoscopic ultrasonography-guided chemotherapeutic seeds implantation for progressive gastric cancer

Objective To evaluate the efficacy of endoscopic ultrasonography（EUS）guided implantation of 5-FU seeds for progressive gastric cancer.Methods A total of 23 patients with progressive gastric cancer and outflow obstruction were enrolled into the study.During the endoscopy procedure, 45-60 5-FU seeds were implanted into the tumors with guidance of EUS, with an average dose of 100 mg.Volumes of tumor were examined with 3D-EUS before and after the treatment.Results A total of 33 procedures of 5-FU implantation were performed.By measurements of 3D-EUS, the numbers of patients with complete respons, partial response, no change, progressive disease were 1, 15, 6 and 1, respectively.In terms of outflow obstruction improvement, significant effect, obvious effect and average effect were achieved in 6, 7 and 9 patients, respectively, with an overall response rate at 91.4%.Conclusion EUS-guided 5-FU seed implantation in progressive gastric cancer is safe,reliable and effective with few complications.3D-EUS may be a new method to evaluate curative effect. Key words: Endoscopic ultrasonography; Gastric cancer; Antineoplastic chemotherapy protocols

Decreased expression of DICER1 in gastric cancer

The role of epigenetics in gene expression regulation and development significantly enhances our understanding of carcinogenesis. All the tumor related genes may be the target of epigenetical or genetic regulation. We selected some epigenetically regulated genes for cDNA array analysis and observed variability in the expression of the DICER1 gene in distinct stages of gastric cancer. The aim of this study was to assess the correlation between the expression of DICER1, an epigenetically regulated gene, and gastric cancer. To detect the expression of 506 tumor-associated genes, including DICER1, in the matched cancerous mucosa, pre-malignant lesion (adjacent mucosa), non-cancerous gastric mucosa and distant lymphocyte metastatic lesion in 3 cases of gastric cancers using cDNA array. DICER1 mRNA expression and DICER1 protein expression were further analyzed by Real-time PCR and Western blot in 32 cases of progressive gastric cancer. DICER1 protein expression was also detected in 33 early and 30 progressive gastric cancers by the immunohistochemistry (IHC) method. In 3 cases of gastric cancer cDNA array showed dramatically decreased expression of DICER1 in pre-malignant lesion, cancerous mucosa and distant lymphocyte metastatic lesions compared with matched noncancerous gastric mucosa, pre-malignant lesion and cancerous mucosa. Real-time PCR results showed that the expression level of DICER1 mRNA in gastric cancer was significantly down-regulated compared to normal gastric tissue (P < 0.05). The IHC assay also showed that the expression of DICER1 was significantly decreased in progressive gastric cancer. Among the 63 cases of gastric cancers, 13/33 early (39.4%) and 19/30 (63.3%) progressive cancers showed negative expression of DICER1 (50.8%). The difference in expression of DICER1 between early and progressive gastric cancers was significant (P < 0.01). The result of Western blotting showed that DICER1 protein was down-regulated significantly in advanced gastric cancer (P < 0.05). DICER1 expression is decreased during the progression of gastric cancer, especially in progressive gastric cancers, which indicating DICER1 may play an important role in the development of cancer and the epigenetical regulation involved.

Expression of the full-length telomerase reverse transcriptase (hTERT) transcript in both malignant and normal gastric tissues

Activation of telomerase by the induction of a full-length telomerase reverse transcriptase (hTERT) transcript is a critical step during cellular immortalization and malignant transformation. Telomerase activity or hTERT expression has thus served as diagnostic and/or prognostic markers in different types of human malignancies. In the present study, we investigated the expression of the telomerase components hTERT and telomerase RNA template (hTER) in normal and malignant gastric tissues derived from 37 patients with gastric cancers. Overall hTERT mRNA was detectable in 33/37 (90%) of tumour specimens and 23/37 (62%) of the corresponding normal gastric tissues. Twenty-five of thirty-seven tumours (71%) expressed the full-length hTERT mRNA, and unexpectedly, this full-length transcript was found in 16 of 37 (43%) normal gastric tissues. Immunohistochemical analyses demonstrated a positive hTERT staining in small fractions of normal epithelial cells and in most gastric cancer cells. A close correlation between the presence of a full-length hTERT transcript and the c-MYC oncogene expression was observed in both normal and cancerous gastric specimens. Moreover, the full-length hTERT expression was positively associated with the tumour size in these patients. Similar levels of hTER expression were expressed in tumour and their corresponding normal tissues. The finding that the full-length hTERT transcript was present in both normal and malignant gastric tissues will preclude its use as a gastric cancer marker. Nevertheless, full-length hTERT mRNA expression may indicate a progressive gastric cancer, and its presence in normal gastric mucosa may have an impact on the anti-telomerase strategy for cancer therapeutic purpose.