BACKGROUND The diagnosis of gastric carcinoma(GC)is essential for improving clinical outcomes.However,the biomarkers currently used for GC screening are not ideal.AIM To explore the diagnostic implications of the neut...BACKGROUND The diagnosis of gastric carcinoma(GC)is essential for improving clinical outcomes.However,the biomarkers currently used for GC screening are not ideal.AIM To explore the diagnostic implications of the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammatory index(SII)for GC.METHODS The baseline data of 133 patients with GC and 134 patients with precancerous gastric conditions admitted between January 2022 and December 2023 were retrospectively analyzed.The information on peripheral blood platelet,neutrophil,and lymphocyte counts in each patient was collected,and the NLR,PLR,and SII levels of both groups were calculated.Additionally,multivariate logistic regression analysis was conducted,and the diagnostic implications of NLR,PLR,and SII in differentiating patients with precancerous gastric conditions,compared with those with GC,were analyzed through receiver operating characteristic(ROC)curves.RESULTS The data indicated that NLR,PLR,and SII had abnormally increased levels in the patients with GC.Gender and body mass index were risk factors for the occurrence of GC.ROC data revealed that the areas under the curve of three patients with precancerous gastric conditions,who were differentiated from those with GC,were 0.824,0.787,and 0.842,respectively.CONCLUSION NLR,PLR,and SII are all abnormally expressed in GC and have diagnostic implications,especially when used as joint indicators,in distinguishing patients with precancerous gastric conditions from those with GC.展开更多
BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial...BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.展开更多
BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnos...BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.展开更多
BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the dif...BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the differences in metabolites between patients with GC and healthy controls,with the objective of identifying potential serum biomarkers for GC diagnosis through a non-targeted metabolomics approach.METHODS An untargeted metabolic analysis was conducted on serum samples from 6 patients with GC and 6 healthy controls.Subsequently,the differential metabolites identified were further validated in serum samples from an expanded cohort of 50 patients with GC and 50 healthy controls.The discriminative capacity of differential metabolites in distinguishing patients with GC from healthy controls was assessed utilizing the receiver operating characteristic curve analysis.The association between the serum levels of differential metabolites and the disease severity,as determined by the tumor-node-metastasis staging system,was evaluated using Spearman’s rank correlation coefficient.RESULTS Our findings revealed a significant alteration in the metabolic profile,characterized by 111 up-regulated and 55 down-regulated metabolites in patients with GC compared to healthy controls.Among the top 10 up-regulated metabolites,the serum concentrations of eight metabolites including fenpiclonil,methyclothiazide,5-hydroxyindoleacetate,3-pyridinecarboxylic acid,guanabenz,2,2-dichloro-N-(3-chloro-1,4-dioxo-2-naphthyl)acetamide,epigallocatechin gallate,and dimethenamid,were further validated to be significantly elevated in a cohort of 50 patients diagnosed with GC compared to 50 healthy control subjects(P<0.001).With the exception of 3-pyridinecarboxylic acid,the area under the curve values for the remaining seven metabolites exceeded 0.7,suggesting that these metabolites possess substantial diagnostic potential for distinguishing patients with GC from healthy individuals.Additionally,the serum concentrations of methyclothiazide(r=0.615,P<0.001),epigallocatechin gallate(r=0.482,P=0.004),and dimethenamid(r=0.634,P<0.001)demonstrated a significant positive correlation with the T stage in patients with GC.The serum concentrations of methyclothiazide(r=0.438,P=0.008)and epigallocatechin gallate(r=0.383,P=0.023)exhibited a significant positive correlation with the N stage in these patients.CONCLUSION This study provides insights into the metabolic alterations associated with GC,and the identification of these biomarkers may enhance the clinical detection and management of the disease.展开更多
BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China,with the disease's intricate and varied characteristics further amplifying its health impact.Precise fore...BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China,with the disease's intricate and varied characteristics further amplifying its health impact.Precise forecasting of overall survival(OS)is of paramount importance for the clinical management of individuals afflicted with this malignancy.AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma.METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020.Least absolute shrinkage and selection operator,univariate,and multivariate Cox regression analyses were employed to identify independent prognostic factors.A nomogram model was developed to predict gastric cancer patient outcomes.The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves.To evaluate the clinical utility of the model,Kaplan-Meier and decision curve analyses were performed.RESULTS A total of ten independent prognostic factors were identified,including body mass index,tumor-node-metastasis(TNM)stage,radiation,chemotherapy,surgery,albumin,globulin,neutrophil count,lactate dehydrogenase,and platelet-to-lymphocyte ratio.The area under the curve(AUC)values for the 1-,3-,and 5-year survival prediction in the training set were 0.843,0.850,and 0.821,respectively.The AUC values were 0.864,0.820,and 0.786 for the 1-,3-,and 5-year survival prediction in the validation set,respectively.The model exhibited strong discriminative ability,with both the time AUC and time C-index exceeding 0.75.Compared with TNM staging,the model demonstrated superior clinical utility.Ultimately,a nomogram was developed via a web-based interface.CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients,which demonstrated strong predictive ability.Based on these findings,this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.展开更多
The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14...The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
We discuss the findings of Wu et al on the utility of neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and systemic immune-inflammatory index as diagnostic markers for gastric carcinoma(GC).We commend the s...We discuss the findings of Wu et al on the utility of neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and systemic immune-inflammatory index as diagnostic markers for gastric carcinoma(GC).We commend the study's contributions to the field and suggest a prospective study to validate these markers'sensitivity and specificity for early GC detection.We also propose developing surveillance protocols that incorporate these markers with other diagnostic methods to enhance clinical decision-making.Furthermore,we highlight the need for a more diverse patient cohort to assess the generalizability of these markers across different ethnic groups and demographic factors.Our suggestions aim to refine the application of these markers in clinical practice and to understand their potential in diverse clinical scenarios.展开更多
Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant pot...Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.展开更多
BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcino...BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.展开更多
Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma c...Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.展开更多
Objective: To study the relationship between the expression of p27Kip1 and p53, and the infiltration, metastasis and prognosis in gastric carcinoma. Methods: The expression of p27Kip1 and p53 at protein level was dete...Objective: To study the relationship between the expression of p27Kip1 and p53, and the infiltration, metastasis and prognosis in gastric carcinoma. Methods: The expression of p27Kip1 and p53 at protein level was determined by immunohistochemical assay (two-step method) in 100 cases of gastric carcinoma. Results: Of the 100 cases, the positive rate of p27Kip1 and p53 expressions were 44% and 49%, respectively. In the group of gastric carcinomas with deep infiltration (infiltration group), lymph nodes metastasis group (metastasis group) and death-within-5-years group (death group), the expression of p27Kip1 was statistically lower (_P<0.05). In the metastasis group and death group, the expression of p53 was significantly higher (P<0.05). The results of the monovariate analysis revealed that the 5-year survival rate of the high p27Kip1 expression group was 70.59%, which is higher than those of the low p27Kip1 expression group (54.55%) and the negative experession group (26%). The 5-year survival rate of the high p53 expression group was 19.23%, which was lower than those of the p53 low expression group (43.75%) and the negative group (53.19%). Cox multivariate analysis showed that p27Kip1, like p53, was an independent prognostic index. But p27Klpl protein expression was a stronger independent survival predictor (RR=3.06) than p53 expression (RR=2.33). Conclusion: The low expression of p27Kip1 and the high expression of p53 reflected the more frequent invasion and metastasis, which resulted in the reduced survival of patients. As an independent markers of the gastric carcinoma, the expression of p27Kip1 is more useful than that of p53 in the prognosis prediction of gastric carcinoma.展开更多
Gastric carcinoma (GC) is the 4<sup>th</sup> most prevalent cancer and has the 2<sup>nd</sup> highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the...Gastric carcinoma (GC) is the 4<sup>th</sup> most prevalent cancer and has the 2<sup>nd</sup> highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.展开更多
AIM: To investigate the inhibitory effect of a specific small survivin interfering RNA (siRNA) on cell proliferation and the expression of survivin in human gastric carcinoma cell line SGC-7901. METHODS: To knockdown ...AIM: To investigate the inhibitory effect of a specific small survivin interfering RNA (siRNA) on cell proliferation and the expression of survivin in human gastric carcinoma cell line SGC-7901. METHODS: To knockdown survivin expression, a small interfering RNA targeting against survivin was synthesized and transfected into SGC-7901 cells with lipofectamineTM2000. The downregulation of survivin expression at both mRNA and protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell proliferation inhibition rates were determined by methyl thiazolyl tetrazolium (MTT) assay. The effect of survivin siRNA on cell cycle distribution and cell apoptosis was determined by flow cytometry (FCM). RESULTS: RNA interference could efficiently suppress the survivin expression in SGC-7901 cells. At 48 h after transfection, the expression inhibition rate was 44.52% at mRNA level detected by RT-PCR and 40.17% at protein level by Western blot analysis. Downregulation of survivin resulted in significant inhibition of tumor cell growth in vitro. The cell proliferation inhibition rates at 24, 48 and 72 h after survivin siRNA and non-siliencing siRNA transfection, were 34.06%, 47.61% and 40.36%, respectively. The apoptosis rate was 3.56% and the number of cells was increased in G0/G1 phase from 38.2% to 88.6%, and decreased in S and G2/M phase at 48 h after transfection. CONCLUSION: Downregulation of survivin results in significant inhibition of tumor growth in vitro. The inhibition of survivin expression can induce apoptosis of SGC-7901 cells. The use of survivin siRNA deserves further investigation as a novel approach to cancer therapy.展开更多
Objective: To investigate the expressions of caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressi...Objective: To investigate the expressions of caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressions with the development of gastric cancer. Methods: The expressions of caveolin-1, E-cadherin and β-catenin were detected by biotin-streptavidinperoxidase (SP) immunohistochemistry on 58 gastric cancer tissues, 40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues. The correlation between the expressions of caveolin-1, E-cadherin and β-catenin, and the clinicopathologic parameters of gastric cancer was analyzed retrospectively. Results: The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues (P〈0.01). An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues (P〈0.01). Moreover, low expressions of caveolin-1, E-cadherin and β-catenin correlated with tumor size, depth of invasion, lymph node metastasis and TNM stage (P〈0.05). The positive rates of caveolin-1 and E-cadherin expressions decreased (P〈0.01), while an abnormal rate of β-catenin expression increased inversely, with the degree of atypical hyperplasia (P〈0.01). Caveolin-1 expression correlated positively with E-cadherin (r=0.41, P〈0.05). Caveolin-1 (r=-0.36, P〈0.05) and E-cadherin (r=-0.45, P〈0.05) expressions negatively correlated with abnormal β-catenin expression. Conclusion: These results suggested that dysregulated expressions of caveolin-1, E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.展开更多
AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loo...AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loop reverse transcriptional primer,the primers and quantitative MGB probes of real-time PCR were designed and synthesized. The dynamic range and the sensitivity of quantitative reverse transcriptional real-time PCR were determined. The levels of let-7a miRNA were examined in 32 gastric carcinoma samples by stem-loop RT-PCR method. RESULTS: The dynamic range and sensitivity of the let-7a miRNA quantification scheme were evaluated,the result showed the assay could precisely detect 10 copies of mature let-7a miRNA in as few as 0.05 ng of total RNA of gastric mucosa. The results of specificity analysis showed no fluorescence signal occurred even though 50 ng of human genomic DNA was added to the reverse transcription (RT) reaction. The expression level of let-7a miRNA in gastric tumor tissues was significantly lower compared to normal tissues in 14 samples from 32 patients. CONCLUSION: The stem-loop RT-PCR is a reliable method to detect let-7a miRNA which may play an important role in the development of gastric carcinoma.展开更多
AIM:To examine the clinicopathologic features of elderly patients with gastric carcinoma and to investigate the relationship between prognosis and age.METHODS: We reviewed the hospital records of 2 014patients with ga...AIM:To examine the clinicopathologic features of elderly patients with gastric carcinoma and to investigate the relationship between prognosis and age.METHODS: We reviewed the hospital records of 2 014patients with gastric carcinoma retrospectively to compare the clinicopathologic findings in elderly (age >70 years) and young (age <36 years) patients during the period from 1986 to 2000 in a tertiary referral center in Gwangju, Korea. Overall survival was the main outcome measure.RESULTS: Of the 2 014 patients, 194 (9.6%) were in the elderly group and 137 (6.8%) were in the young group.The elderly and young patients had similar distributions with respect to depth of invasion, nodal involvement, hepatic metastasis, peritoneal dissemination, tumor stage at the initial diagnosis, and type of surgery. Synchronous multiple carcinomas were found in 14/194 (7.2%) of the elderly group and 4/137 (2.9%) of the young group (P<0.05). Using the Borrmann classification, type Ⅳ was more frequent in the young patients than in the elderly patients (P<0.05).Significantly more elderly patients had a well or moderately differentiated histology, and more young patients had a poorly differentiated histology and signet ring cell carcinoma (P<0.001). The 5-year survival rates of elderly and young patients did not differ statistically (52.8% vs 46.5%,P = 0.5290). Multivariate analysis showed that the histologic type, nodal involvement and operative curability were significant prognostic factors, and age itself was not an independent prognostic factor of survival for elderly gastric carcinoma patients.CONCLUSION: Elderly patients with gastric carcinoma do not have a worse prognosis than young patients. The important prognostic factor is whether the patients undergo a curative resection.展开更多
AIM: To examine matrix metalloproteinase-2 (MMP-2) expression in gastric cancer tissues and to evaluate its relationship with lymph node micrometastasis. MATERIALS: The authors studied 850 lymph nodes resected fro...AIM: To examine matrix metalloproteinase-2 (MMP-2) expression in gastric cancer tissues and to evaluate its relationship with lymph node micrometastasis. MATERIALS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenetomy using reverse transcription polymerase chain reaction (RT-PCR) assay in addition to H-E staining. MMP-2 expression of the tumor tissues was detected by immunohistochemical technique (EliVision^TM plus). RESULTS: MMP-2 expression was positive in 21 (70%) cases and negative in g (30%) cases. No significant correlations were found between MMP-2 expression and other variables such as age, gender, tumor location, tumor diameter, Lauren classification and lymphatic invasion. In contrast, MMP-2 expression correlated significantly with depth of tumor infiltration (P = 0.022), lymph node metastasis (P = 0.030) and tumor differentiation (P = 0.043). Lymph node micrometastases were detected in 77 (12.5%) lymph nodes of 14 (46.7%) gastric carcinoma patients. MMP-2 expression was positive in 12 (85.7%) of the 14 patients with lymph node micrometastasis, and in g (56.3%) of the 16 patients without lymph node micrometastasis (P = 0.118). CONCLUSIONS: Our results demonstrate that MMP-2 expression has significant correlation with tumor invasion, tumor differentiation and lymph node metastases. MMP-2 expression may be an important biological characteristics and significant prognostic parameter of gastric carcinoma. We also conclude that MMP-2 may participate in the development of lymph node micrometastasis of gastric carcinoma. Further investigations are needed to draw a conclusion.展开更多
AIM:To study the HER-2/neu protein expression and gene amplification in gastric carcinoma and their relation.METHODS:One hundred and forty-five formalin-fixed and paraffin-embedded tumor tissue samples from Chinese ga...AIM:To study the HER-2/neu protein expression and gene amplification in gastric carcinoma and their relation.METHODS:One hundred and forty-five formalin-fixed and paraffin-embedded tumor tissue samples from Chinese gastric carcinoma patients were studied with immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH)methods.Clinicopathologic data about all patients were collected.RESULTS:The levels of HER-2 3+,HER-2 2+and HER21+were measurable in 6.9%,8.3%and 17.2%of the samples,respectively.No HER-2 was stained in 67.6% of the samples.FISH showed that HER-2 gene was amplified in 18 samples,10 HER-2 3+samples,5 HER-2 2+samples,and 3 HER-2 1+samples with IHC staining.HER-2 status was not correlated with the sex and age of patients,and tumor size,location or differentiation,but with the depth of invasion,TNM stage,lymph node and distant metastasis as well as histopathological classification of gastric cancer(P<0.05).CONCLUSION:All samples with IHC as HER-2 expression should be analyzed with FISH.Detection of HER-2 gene amplification can assess the malignant biological behaviors and prognosis of gastric cancer.展开更多
AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected w...AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.展开更多
AIM: To investigate the effect of arsenic trioxide on human gastric cancer cell line MKN45 with respect to both cytotoxicity and induction of apoptosis in vitro. METHODS: MKN45 cells were treated with arsenic trioxide...AIM: To investigate the effect of arsenic trioxide on human gastric cancer cell line MKN45 with respect to both cytotoxicity and induction of apoptosis in vitro. METHODS: MKN45 cells were treated with arsenic trioxide (As2O3) at the concentration of 1, 5, and 10 μmol/L, respectively, for three successive days. Cell growth and proliferation were observed by cell counting and trypan blue exclusion. Cytotoxicity of As2O3 was determined by MTT assay. Morphologic changes were studied with light microscopy. Flow cytometry was used to assay cell DNA distribution and apoptotic cells were confirmed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and DNA electrophoresis. RESULTS: The growth of MKN45 cells was significantly inhibited by As2O3 which was confirmed by colony-forming assay. After 7 d of culture with various concentrations of As2O3, colony-forming capacity of MKN45 cells decreased with As2O3 increment in comparison with that of control group. The inhibitory rate of colony-formation was 38.5%, 99.1%, and 99.5% when the concentration of As2O3 was 1, 5, and 10 μmol/L in culture medium, respectively. The cell number of a single colony in drug treatment groups was less than that of control group. The cell-killing rate of As2O3 to MKN45 cells was both dose- and time-dependent with an IC50 of (11.05±0.25) μmol/L After incubation in 10 μmol/L As2O3 for 24 h, the cell-killing rate was 27.1%, and it was close to 50% after 48 h. The results showed that As2O3 induced time- and dose-dependent apoptosis in MKN45 cells, blocked at G2/M phase. The apoptotic peak (sub-G1 phase) appeared and cell apoptotic rate in MKN45 cells was 18.3-32.5% after treatment by 10 umol/L As2O3 for 48 h. The percentage of G2/M cell of the experimental groups was 2.0-5.0 times than that of the control group. Gel electrophoresis of DNA from cells treated with each concentration of As2O3 for 48 h revealed a 'ladder' pattern, indicating preferential DNA degradation at the internucleosomal, linker DNA sections. TUNEL also demonstrated strand breaks in DNA of MKN45 cells treated with As2O3, while control cells showed negative labeling. CONCLUSION: As2O3 can induce apoptosis of human gastric carcinoma cells MKN45, which is the basis of its effectiveness. It shows great potential in the treatment of gastric carcinoma.展开更多
文摘BACKGROUND The diagnosis of gastric carcinoma(GC)is essential for improving clinical outcomes.However,the biomarkers currently used for GC screening are not ideal.AIM To explore the diagnostic implications of the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammatory index(SII)for GC.METHODS The baseline data of 133 patients with GC and 134 patients with precancerous gastric conditions admitted between January 2022 and December 2023 were retrospectively analyzed.The information on peripheral blood platelet,neutrophil,and lymphocyte counts in each patient was collected,and the NLR,PLR,and SII levels of both groups were calculated.Additionally,multivariate logistic regression analysis was conducted,and the diagnostic implications of NLR,PLR,and SII in differentiating patients with precancerous gastric conditions,compared with those with GC,were analyzed through receiver operating characteristic(ROC)curves.RESULTS The data indicated that NLR,PLR,and SII had abnormally increased levels in the patients with GC.Gender and body mass index were risk factors for the occurrence of GC.ROC data revealed that the areas under the curve of three patients with precancerous gastric conditions,who were differentiated from those with GC,were 0.824,0.787,and 0.842,respectively.CONCLUSION NLR,PLR,and SII are all abnormally expressed in GC and have diagnostic implications,especially when used as joint indicators,in distinguishing patients with precancerous gastric conditions from those with GC.
基金Supported by Liaoning Provincial Science and Technology Plan Joint Plan,No.2023JH2/101700149。
文摘BACKGROUND The deleterious effects of surgical trauma and subsequent postoperative complications pose significant challenges to the smooth recovery of patients after gastric cancer(GC)resection despite the substantial curative benefits provided by surgical interventions for GC.Hence,the investigation of more optimal and efficacious treatment approaches has become an urgent necessity in the medical community.AIM To investigate the association of Sijunzi decoction plus chemotherapy with the gastrointestinal function and serum markers of patients after GC surgery.METHODS This study included patients who underwent GC surgery from June 2022 to February 2024.The control group included 45 patients who received chemotherapy(oxaliplatin+calcium folinate+5-fluorouracil),whereas the research group consisted of 54 patients who received Sijunzi decoction therapy in addition to the treatment administered in the control group.Comparative analyses were conducted from the following perspectives:Gastrointestinal function(defecation time,intestinal gas discharge time,and hospitalization time),serum markers[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,and CA199],nutritional indicators total protein(TP)and transferrin(TRF),traditional Chinese medicine(TCM)syndrome score,and grades Ⅲ–Ⅳ adverse events(gastrointestinal reactions,renal/liver function impairment,and myelosuppression).RESULTS The two groups demonstrated similar defecation time(P>0.05),but the intestinal gas discharge time and hospitalization time were significantly shortened in the research group(P<0.05).Further,the research group exhibited significant CEA,CA125,and CA199 reductions after treatment,which were lower compared to the control group,as well as notable increases in TP and TRF that were statistically higher than the control group(all P<0.05).Furthermore,the research group demonstrated an evident decrease in TCM syndrome scores in areas,such as poor appetite,epigastric distension and pain,fatigue and weakness(P<0.01),and abdominal distension after eating,which are notably lower than those in the control group(P<0.01),with a comparable incidence of grades Ⅲ-Ⅳ adverse events(P>0.05).CONCLUSION Our research results indicate that Sijunzi decoction plus chemotherapy exerts a good rehabilitation-promoting effect on gastrointestinal function in patients after GC surgery and significantly downregulates abnormally increased CEA,CA125,and CA199 levels.
文摘BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.
文摘BACKGROUND In recent years,metabolomics has emerged as a novel platform for biomarker discovery.However,the metabolic profiles associated with gastric carcinoma(GC)remain insufficiently explored.AIM To examine the differences in metabolites between patients with GC and healthy controls,with the objective of identifying potential serum biomarkers for GC diagnosis through a non-targeted metabolomics approach.METHODS An untargeted metabolic analysis was conducted on serum samples from 6 patients with GC and 6 healthy controls.Subsequently,the differential metabolites identified were further validated in serum samples from an expanded cohort of 50 patients with GC and 50 healthy controls.The discriminative capacity of differential metabolites in distinguishing patients with GC from healthy controls was assessed utilizing the receiver operating characteristic curve analysis.The association between the serum levels of differential metabolites and the disease severity,as determined by the tumor-node-metastasis staging system,was evaluated using Spearman’s rank correlation coefficient.RESULTS Our findings revealed a significant alteration in the metabolic profile,characterized by 111 up-regulated and 55 down-regulated metabolites in patients with GC compared to healthy controls.Among the top 10 up-regulated metabolites,the serum concentrations of eight metabolites including fenpiclonil,methyclothiazide,5-hydroxyindoleacetate,3-pyridinecarboxylic acid,guanabenz,2,2-dichloro-N-(3-chloro-1,4-dioxo-2-naphthyl)acetamide,epigallocatechin gallate,and dimethenamid,were further validated to be significantly elevated in a cohort of 50 patients diagnosed with GC compared to 50 healthy control subjects(P<0.001).With the exception of 3-pyridinecarboxylic acid,the area under the curve values for the remaining seven metabolites exceeded 0.7,suggesting that these metabolites possess substantial diagnostic potential for distinguishing patients with GC from healthy individuals.Additionally,the serum concentrations of methyclothiazide(r=0.615,P<0.001),epigallocatechin gallate(r=0.482,P=0.004),and dimethenamid(r=0.634,P<0.001)demonstrated a significant positive correlation with the T stage in patients with GC.The serum concentrations of methyclothiazide(r=0.438,P=0.008)and epigallocatechin gallate(r=0.383,P=0.023)exhibited a significant positive correlation with the N stage in these patients.CONCLUSION This study provides insights into the metabolic alterations associated with GC,and the identification of these biomarkers may enhance the clinical detection and management of the disease.
文摘BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China,with the disease's intricate and varied characteristics further amplifying its health impact.Precise forecasting of overall survival(OS)is of paramount importance for the clinical management of individuals afflicted with this malignancy.AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma.METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020.Least absolute shrinkage and selection operator,univariate,and multivariate Cox regression analyses were employed to identify independent prognostic factors.A nomogram model was developed to predict gastric cancer patient outcomes.The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves.To evaluate the clinical utility of the model,Kaplan-Meier and decision curve analyses were performed.RESULTS A total of ten independent prognostic factors were identified,including body mass index,tumor-node-metastasis(TNM)stage,radiation,chemotherapy,surgery,albumin,globulin,neutrophil count,lactate dehydrogenase,and platelet-to-lymphocyte ratio.The area under the curve(AUC)values for the 1-,3-,and 5-year survival prediction in the training set were 0.843,0.850,and 0.821,respectively.The AUC values were 0.864,0.820,and 0.786 for the 1-,3-,and 5-year survival prediction in the validation set,respectively.The model exhibited strong discriminative ability,with both the time AUC and time C-index exceeding 0.75.Compared with TNM staging,the model demonstrated superior clinical utility.Ultimately,a nomogram was developed via a web-based interface.CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients,which demonstrated strong predictive ability.Based on these findings,this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.
文摘The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘We discuss the findings of Wu et al on the utility of neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,and systemic immune-inflammatory index as diagnostic markers for gastric carcinoma(GC).We commend the study's contributions to the field and suggest a prospective study to validate these markers'sensitivity and specificity for early GC detection.We also propose developing surveillance protocols that incorporate these markers with other diagnostic methods to enhance clinical decision-making.Furthermore,we highlight the need for a more diverse patient cohort to assess the generalizability of these markers across different ethnic groups and demographic factors.Our suggestions aim to refine the application of these markers in clinical practice and to understand their potential in diverse clinical scenarios.
基金This study was supported by the Key Clinical Project of the Chinese Ministry of Health (No. 20012130)
文摘Objective: To study the expression of cyclooxygenase-2 (COX-2) protein in different subtypes of intestinal metaplasia (IM) and gastric carcinoma, evaluate the possibility of COX-2 forecasting the risk of malignant potential of IM, and the relationship between COX-2 expression and gastric carcinogenesis. Methods: Forty cases of chronic atrophic gastritis (CAG) with IM, 40 cases of gastric carcinoma and corresponding paracancerous tissues were selected to construct a tissue microarray. High iron diamine/alcian blue (HID/AB) staining and Hematoxylin and Eosin (HE) staining was used to classify IM and gastric carcinoma, and the expression of COX-2 protein detected in different subtypes of IM and gastric cancer by using immunohistochemistry. Results: The positive expression rate of COX-2 was 45.65%, 59.38% and 77.27% in IM foci in CAG, IM foci in paracancerous tissues, and intestinal-type gastric carcinoma, respectively, significantly higher than in diffuse-type gastric cancer (16.67%)(P<0.05, 0.005 and 0.005, respectively), and the expression intensity of COX-2 protein showed a increased tendency gradually in the sequence of IM foci in CAG→IM foci in paracancerous tissues→intestinal-type gastric carcinoma (P<0.005). The positive expression rate of COX-2 protein in type Ⅲ IM was significantly higher than in type Ⅰ and type Ⅱ IM (P<0.005 and 0.05, respectively), and the expression intensity also showed a increased tendency gradually from type Ⅰ to type Ⅲ IM (P<0.005). Conclusion: The expression level of COX-2 was increased gradually along with the increase of the risk of malignancy of IM, and its expression level may be a useful index to forecast the risk of malignant potential of IM. COX-2 expression was associated with intestinal-type gastric carcinoma, but it might also have some role in the carcinogenesis of diffuse-type gastric carcinoma.
基金Supported by the National Key Research and Development Program of China,No.2023YFF1204702the National Natural Science Foundation of China,No.82173151+2 种基金Capital’s Funds for Health Improvement and Research,No.CFH 2022-4-1025Beijing Hospitals Authority Clinical Medicine Development of Special Funding,No.XMLX202119Science Foundation of Peking University Cancer Hospital,No.PY202329.
文摘BACKGROUND Gastric mixed-adenoneuroendocrine carcinoma(G-MANEC)is a subtype of gastric cancer.Building upon prior research findings,we propose that tumours containing both neuroendocrine carcinoma(NEC)and adenocarcinoma(AC)components,with each component ranging from 1%to 99%of the tumour,be classified as a distinct entity.We hereby term this adenoneuroendocrine mixed gastric cancer(G-ANEC).Research on lymph node(LN)involvement in GMANEC has focused mainly on metastasis status,with limited studies on metastatic composition.AIM To investigate the LN metastasis patterns of G-ANEC,the clinicopathological features associated with these metastasis patterns,and to explore adjuvant chemotherapy regimens for G-ANEC.METHODS We analyzed 68 G-ANEC cases treated with radical surgery and confirmed LN metastasis at Peking University Cancer Hospital between August 2012 and June 2022.Utilizingχ2 tests in IBM statistical product and service solutions statistics and R software.RESULTS We identified three distinct LN metastasis patterns in G-ANEC that were significantly associated with the NEC proportion,tumour invasion depth,Lauren classification,and tumour location(P values:0.008,0.015,0.01,and 0.004,respectively).When the SOX/XELOX regimen was applied for adjuvant chemotherapy,patients with LN metastasis comprising only AC exhibited better overall survival(OS)(94.25±11.07 months vs 54.36±11.36 months)than did those with NEC.When LN metastasis components contained NEC,there was a trend towards improved OS(64±10.77 months vs 54.35±11.36 months)and disease-free survival(71.28±9.92 months vs 66.28±11.93 months)in patients treated with the etoposide and cisplatin compared to those receiving the SOX/XELOX regimen.CONCLUSION We found a significant correlation between the NEC percentage,tumour invasion depth,Lauren classification,and tumour location and LN metastasis patterns in G-ANEC.For G-ANEC,a lower proportion of NEC or AC in the primary lesion does not preclude the possibility of these components metastasizing to the LNs.Different adjuvant chemotherapy regimens should be administered on the basis of the varying components of LN metastasis in patients with G-ANEC.
文摘Objective: To study the expression of vascular endothelial growth factor C (VEGF-C) in gastric carcinoma and its relationship with lymph node metastasis. Methods: The expression of VEGF-C mRNA in 5 gastric carcinoma cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR). Simultaneously, the expression of VEGF-C protein in gastric carcinoma tissues, which were obtained from 63 patients who underwent radical gastrectomy, was detected by immunohistochemistry. Results: Three of the 5 gastric carcinoma cell lines, MKN-45, SGC-7901 and AGS, expressed VEGF-C mRNA. VEGF-C protein was expressed in 52.4% (33/63) of patients. VEGF-C protein expression was more frequently found in tumors with lymph node metastasis than in those without (P<0.01). VEGF-C protein expression was also closely related to lymphatic invasion (P<0.01) and TNM stage (P<0.01). However, there was no significant correlation between VEGF-C expression and the age, gender, tumor size, tumor location, Lauren classification, depth of invasion, and vascular invasion. Conclusion: The expression of VEGF-C is closely related to lymph node metastasis of gastric carcinoma, and lymphangiogenesis might be a new target for treatment of gastric carcinoma.
文摘Objective: To study the relationship between the expression of p27Kip1 and p53, and the infiltration, metastasis and prognosis in gastric carcinoma. Methods: The expression of p27Kip1 and p53 at protein level was determined by immunohistochemical assay (two-step method) in 100 cases of gastric carcinoma. Results: Of the 100 cases, the positive rate of p27Kip1 and p53 expressions were 44% and 49%, respectively. In the group of gastric carcinomas with deep infiltration (infiltration group), lymph nodes metastasis group (metastasis group) and death-within-5-years group (death group), the expression of p27Kip1 was statistically lower (_P<0.05). In the metastasis group and death group, the expression of p53 was significantly higher (P<0.05). The results of the monovariate analysis revealed that the 5-year survival rate of the high p27Kip1 expression group was 70.59%, which is higher than those of the low p27Kip1 expression group (54.55%) and the negative experession group (26%). The 5-year survival rate of the high p53 expression group was 19.23%, which was lower than those of the p53 low expression group (43.75%) and the negative group (53.19%). Cox multivariate analysis showed that p27Kip1, like p53, was an independent prognostic index. But p27Klpl protein expression was a stronger independent survival predictor (RR=3.06) than p53 expression (RR=2.33). Conclusion: The low expression of p27Kip1 and the high expression of p53 reflected the more frequent invasion and metastasis, which resulted in the reduced survival of patients. As an independent markers of the gastric carcinoma, the expression of p27Kip1 is more useful than that of p53 in the prognosis prediction of gastric carcinoma.
文摘Gastric carcinoma (GC) is the 4<sup>th</sup> most prevalent cancer and has the 2<sup>nd</sup> highest cancer-related mortality rate worldwide. Despite the incidence of GC has decreased over the past few decades, it is still a serious health problem. Chronic inflammatory status of the stomach, caused by the infection of Helicobacter pylori (H. pylori) and through the production of inflammatory mediators within the parenchyma is suspected to play an important role in the initiation and progression of GC. In this review, the correlation between chronic inflammation and H. pylori infection as an important factor for the development of GC will be discussed. Major components, including tumor-associated macrophages, lymphocytes, cancer-associated fibroblasts, angiogenic factors, cytokines, and chemokines of GC microenvironment and their mechanism of action on signaling pathways will also be discussed. Increasing our understanding of how the components of the tumor microenviroment interact with GC cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.
文摘AIM: To investigate the inhibitory effect of a specific small survivin interfering RNA (siRNA) on cell proliferation and the expression of survivin in human gastric carcinoma cell line SGC-7901. METHODS: To knockdown survivin expression, a small interfering RNA targeting against survivin was synthesized and transfected into SGC-7901 cells with lipofectamineTM2000. The downregulation of survivin expression at both mRNA and protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell proliferation inhibition rates were determined by methyl thiazolyl tetrazolium (MTT) assay. The effect of survivin siRNA on cell cycle distribution and cell apoptosis was determined by flow cytometry (FCM). RESULTS: RNA interference could efficiently suppress the survivin expression in SGC-7901 cells. At 48 h after transfection, the expression inhibition rate was 44.52% at mRNA level detected by RT-PCR and 40.17% at protein level by Western blot analysis. Downregulation of survivin resulted in significant inhibition of tumor cell growth in vitro. The cell proliferation inhibition rates at 24, 48 and 72 h after survivin siRNA and non-siliencing siRNA transfection, were 34.06%, 47.61% and 40.36%, respectively. The apoptosis rate was 3.56% and the number of cells was increased in G0/G1 phase from 38.2% to 88.6%, and decreased in S and G2/M phase at 48 h after transfection. CONCLUSION: Downregulation of survivin results in significant inhibition of tumor growth in vitro. The inhibition of survivin expression can induce apoptosis of SGC-7901 cells. The use of survivin siRNA deserves further investigation as a novel approach to cancer therapy.
基金supported by Zhejiang Provincial Natural Science Foundation (No. Y206750)Zhejiang Foundation for Development of Science and Technology, China (No. 2008C33066)Wenzhou Foundation for Development of Science and Technology,China (No. H20060026)
文摘Objective: To investigate the expressions of caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous gastric and chronic non-atrophic gastritis tissues, and evaluate the correlation of these expressions with the development of gastric cancer. Methods: The expressions of caveolin-1, E-cadherin and β-catenin were detected by biotin-streptavidinperoxidase (SP) immunohistochemistry on 58 gastric cancer tissues, 40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues. The correlation between the expressions of caveolin-1, E-cadherin and β-catenin, and the clinicopathologic parameters of gastric cancer was analyzed retrospectively. Results: The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues (P〈0.01). An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues (P〈0.01). Moreover, low expressions of caveolin-1, E-cadherin and β-catenin correlated with tumor size, depth of invasion, lymph node metastasis and TNM stage (P〈0.05). The positive rates of caveolin-1 and E-cadherin expressions decreased (P〈0.01), while an abnormal rate of β-catenin expression increased inversely, with the degree of atypical hyperplasia (P〈0.01). Caveolin-1 expression correlated positively with E-cadherin (r=0.41, P〈0.05). Caveolin-1 (r=-0.36, P〈0.05) and E-cadherin (r=-0.45, P〈0.05) expressions negatively correlated with abnormal β-catenin expression. Conclusion: These results suggested that dysregulated expressions of caveolin-1, E-cadherin and β-catenin correlated with the development of gastric cancer and its biological behavior.
文摘AIM: To establish an accurate and rapid stem-loop reverse transcriptional real-time PCR (RT-PCR) method to quantify human let-7a miRNA in gastric cancer. METHODS: According to the sequence of let-7a miRNA,the stem-loop reverse transcriptional primer,the primers and quantitative MGB probes of real-time PCR were designed and synthesized. The dynamic range and the sensitivity of quantitative reverse transcriptional real-time PCR were determined. The levels of let-7a miRNA were examined in 32 gastric carcinoma samples by stem-loop RT-PCR method. RESULTS: The dynamic range and sensitivity of the let-7a miRNA quantification scheme were evaluated,the result showed the assay could precisely detect 10 copies of mature let-7a miRNA in as few as 0.05 ng of total RNA of gastric mucosa. The results of specificity analysis showed no fluorescence signal occurred even though 50 ng of human genomic DNA was added to the reverse transcription (RT) reaction. The expression level of let-7a miRNA in gastric tumor tissues was significantly lower compared to normal tissues in 14 samples from 32 patients. CONCLUSION: The stem-loop RT-PCR is a reliable method to detect let-7a miRNA which may play an important role in the development of gastric carcinoma.
文摘AIM:To examine the clinicopathologic features of elderly patients with gastric carcinoma and to investigate the relationship between prognosis and age.METHODS: We reviewed the hospital records of 2 014patients with gastric carcinoma retrospectively to compare the clinicopathologic findings in elderly (age >70 years) and young (age <36 years) patients during the period from 1986 to 2000 in a tertiary referral center in Gwangju, Korea. Overall survival was the main outcome measure.RESULTS: Of the 2 014 patients, 194 (9.6%) were in the elderly group and 137 (6.8%) were in the young group.The elderly and young patients had similar distributions with respect to depth of invasion, nodal involvement, hepatic metastasis, peritoneal dissemination, tumor stage at the initial diagnosis, and type of surgery. Synchronous multiple carcinomas were found in 14/194 (7.2%) of the elderly group and 4/137 (2.9%) of the young group (P<0.05). Using the Borrmann classification, type Ⅳ was more frequent in the young patients than in the elderly patients (P<0.05).Significantly more elderly patients had a well or moderately differentiated histology, and more young patients had a poorly differentiated histology and signet ring cell carcinoma (P<0.001). The 5-year survival rates of elderly and young patients did not differ statistically (52.8% vs 46.5%,P = 0.5290). Multivariate analysis showed that the histologic type, nodal involvement and operative curability were significant prognostic factors, and age itself was not an independent prognostic factor of survival for elderly gastric carcinoma patients.CONCLUSION: Elderly patients with gastric carcinoma do not have a worse prognosis than young patients. The important prognostic factor is whether the patients undergo a curative resection.
基金Supported by the National Nature Science Foundation of China, No. 30271276
文摘AIM: To examine matrix metalloproteinase-2 (MMP-2) expression in gastric cancer tissues and to evaluate its relationship with lymph node micrometastasis. MATERIALS: The authors studied 850 lymph nodes resected from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenetomy using reverse transcription polymerase chain reaction (RT-PCR) assay in addition to H-E staining. MMP-2 expression of the tumor tissues was detected by immunohistochemical technique (EliVision^TM plus). RESULTS: MMP-2 expression was positive in 21 (70%) cases and negative in g (30%) cases. No significant correlations were found between MMP-2 expression and other variables such as age, gender, tumor location, tumor diameter, Lauren classification and lymphatic invasion. In contrast, MMP-2 expression correlated significantly with depth of tumor infiltration (P = 0.022), lymph node metastasis (P = 0.030) and tumor differentiation (P = 0.043). Lymph node micrometastases were detected in 77 (12.5%) lymph nodes of 14 (46.7%) gastric carcinoma patients. MMP-2 expression was positive in 12 (85.7%) of the 14 patients with lymph node micrometastasis, and in g (56.3%) of the 16 patients without lymph node micrometastasis (P = 0.118). CONCLUSIONS: Our results demonstrate that MMP-2 expression has significant correlation with tumor invasion, tumor differentiation and lymph node metastases. MMP-2 expression may be an important biological characteristics and significant prognostic parameter of gastric carcinoma. We also conclude that MMP-2 may participate in the development of lymph node micrometastasis of gastric carcinoma. Further investigations are needed to draw a conclusion.
基金Supported by National Natural Science Foundation of China, No.81071888
文摘AIM:To study the HER-2/neu protein expression and gene amplification in gastric carcinoma and their relation.METHODS:One hundred and forty-five formalin-fixed and paraffin-embedded tumor tissue samples from Chinese gastric carcinoma patients were studied with immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH)methods.Clinicopathologic data about all patients were collected.RESULTS:The levels of HER-2 3+,HER-2 2+and HER21+were measurable in 6.9%,8.3%and 17.2%of the samples,respectively.No HER-2 was stained in 67.6% of the samples.FISH showed that HER-2 gene was amplified in 18 samples,10 HER-2 3+samples,5 HER-2 2+samples,and 3 HER-2 1+samples with IHC staining.HER-2 status was not correlated with the sex and age of patients,and tumor size,location or differentiation,but with the depth of invasion,TNM stage,lymph node and distant metastasis as well as histopathological classification of gastric cancer(P<0.05).CONCLUSION:All samples with IHC as HER-2 expression should be analyzed with FISH.Detection of HER-2 gene amplification can assess the malignant biological behaviors and prognosis of gastric cancer.
文摘AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved. METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique. RT-PCR, Western blotting, EMSA, gelatin zymography assay, and in vitro invasion and migration assays were performed. Nude mice metastasis models were established by the abdominal cavity transfer method. RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained. Compared with MKN28 and pcDNA3-MKN28 cells, adherence, migration and invasion ability of TwistS -MKN28 cells were clearly raised. The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells. Overexpression of Twist in MKN28 cells increased Tcf-4/ Lef DNA binding activity, and promoted expression of Tcf-4’s downstream target genes cyclin D1 and MMP-2. However, suppression of Twist (TwistAS-MKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced. The activity of MMP-2 was also decreased. CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/ Tcf-4 signaling.
基金Supported by the Zhejiang Province Science and Technology Fund for excellent returnee 2001-275
文摘AIM: To investigate the effect of arsenic trioxide on human gastric cancer cell line MKN45 with respect to both cytotoxicity and induction of apoptosis in vitro. METHODS: MKN45 cells were treated with arsenic trioxide (As2O3) at the concentration of 1, 5, and 10 μmol/L, respectively, for three successive days. Cell growth and proliferation were observed by cell counting and trypan blue exclusion. Cytotoxicity of As2O3 was determined by MTT assay. Morphologic changes were studied with light microscopy. Flow cytometry was used to assay cell DNA distribution and apoptotic cells were confirmed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and DNA electrophoresis. RESULTS: The growth of MKN45 cells was significantly inhibited by As2O3 which was confirmed by colony-forming assay. After 7 d of culture with various concentrations of As2O3, colony-forming capacity of MKN45 cells decreased with As2O3 increment in comparison with that of control group. The inhibitory rate of colony-formation was 38.5%, 99.1%, and 99.5% when the concentration of As2O3 was 1, 5, and 10 μmol/L in culture medium, respectively. The cell number of a single colony in drug treatment groups was less than that of control group. The cell-killing rate of As2O3 to MKN45 cells was both dose- and time-dependent with an IC50 of (11.05±0.25) μmol/L After incubation in 10 μmol/L As2O3 for 24 h, the cell-killing rate was 27.1%, and it was close to 50% after 48 h. The results showed that As2O3 induced time- and dose-dependent apoptosis in MKN45 cells, blocked at G2/M phase. The apoptotic peak (sub-G1 phase) appeared and cell apoptotic rate in MKN45 cells was 18.3-32.5% after treatment by 10 umol/L As2O3 for 48 h. The percentage of G2/M cell of the experimental groups was 2.0-5.0 times than that of the control group. Gel electrophoresis of DNA from cells treated with each concentration of As2O3 for 48 h revealed a 'ladder' pattern, indicating preferential DNA degradation at the internucleosomal, linker DNA sections. TUNEL also demonstrated strand breaks in DNA of MKN45 cells treated with As2O3, while control cells showed negative labeling. CONCLUSION: As2O3 can induce apoptosis of human gastric carcinoma cells MKN45, which is the basis of its effectiveness. It shows great potential in the treatment of gastric carcinoma.