Expression of E-selectin, integrinβ_1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance

AIM： To study the expression levels of E-selectin, integrin β1 and immunoglobulin supperfamily memberintercellular adhesion molecule-1 （ICAM-1） in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma. METHODS： The serum contents of E-selectin, integrin β1 and ICAM-1 were detected by enzyme-linked immunosorbent assay （ELISA）, in 47 healthy individuals （control group） and in 57 patients with gastric carcinoma （gastric carcinoma group） respectively prior to operation and 7 d after operation. RESULTS： The serum E-selectin, ECAM-1 and integrin β1 were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrin β1 were significantly higher in gastric carcinoma patients than in controls （P 〈 0.01）. A comparison of the E-selectin levels between the two groups showed statistically insignificant differnce （P = 0.64）. In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients. CONCLUSION： Serum E-selectin, ICAM-1 and integrin β1 expression levels are probably related to the metastasis and relapse of gastric cancer.

Low intensity ultrasound-induced apoptosis in human gastric carcinoma cells

AIM： To investigate the low intensity ultrasound （US）- induced apoptosis in human gastric carcinoma cells and its potential mechanism and to suggest a new therapeutic approach to gastric carcinoma. METHODS： Human SGC-7901 gastric carcinoma cells were cultured in vitro and irradiated by low intensity US for 10 min at different intensities with different incubation times after irradiation. Morphologic changes were examined under microscope with trypan blue staining and then the percentage of early apoptotic cells was detected by flow cytometry （FCM） with double staining of fiuorescein isothiocyanate （FITC）- Annexin V/propidium iodide （PI）. Two-dimensional electrophoresis （2DE） was used to get the protein profile and some proteins differently expressed after US irradiation were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. Functional analysis was performed to investigate the mechanism of US-induced cell apoptosis. RESULTS： The percentage of apoptotic cells increased about 10% after US irradiation （12.0 W/cm^2, 12 h culture）, The percentage of early apoptosis and secondary necrosis in the US-irradiated cells increased with the increased US intensity. Moreover, apoptotic cells increased with the increased culture time after US irradiation and reached its maximum at about 12 h.Several new proteins appeared after US irradiation and were up or down regulated more than 2 times. Some heat shock proteins （HSPs） were found to be associated with the signal process simulating the apoptosis of cells. CONCLUSION： Low intensity US could induce apoptosis in human gastric carcinoma cells. US-induced apoptosis is related to US intensity/culture time. US-induced apoptosis may be caspases-dependent and endoplasmic reticulum （ER） stress-triggered apoptosis may also contribute to it. Proteomic experimental system is useful in finding the protein alteration in carcinoma cells after US irradiation, helping to develop a new cancer therapy.

Inhibition of human gastric carcinoma cell growth by atofluding derivative N_3-o-toluyl-fluorouracil

AIM： To evaluate the growth inhibition efficacy of atofluding derivative N3-o-toluyl-fluorouracil （TFU） on human gastric carcinoma cell lines SGC-7901 and MKN-45. METHODS： Cell growth inhibition by TFU was measured by MTT and clonogenic assays without or with liver microsomal enzymes. Xenografts of cancer cells in nude mice were employed to study the anti-proliferative effects of TFU in vivo. RESULTS： TFU inhibited the growth of SGC-7901 and MKN-45 cells. However, the inhibitory effects of TFU on cell growth were not significant. The inhibition rates were enhanced in the presence of liver microsomal enzymes, ranging 4.73%-48.57% in SGC-7901 cells and 9.0%-62.02% in MKN-45 cells. In v/vo, TFU delayed the growth of SGC-7901 and MKN-45 cells in nude mice. The inhibition rates were 40.49%, 63.24%, and 75.98% in SGC-7901 cells and 40.76%, 61.41%, and 82.07% in MKN-45 cells when the oral doses were 25, 50, and 100 mg/kg, respectively. TFU treatment was generally well tolerated by mice with less than 20% reduction in body weight. CONCLUSION： TFU inhibits the growth of human gastric carcinoma cells. The inhibition rates are increased in the presence of liver microsomal enzymes. The efficacy of TFU may be associated with the sustaining release of 5-fluorouracil （5-FU） mediated by the enzymes.

Inhibitory effect of Fuzheng Yiliuyin in combination with chemotherapeutics on human gastric carcinoma cell strain

AIM： To study the inhibitory effects of Fuzheng Yiliuyin （Decoction for Suppressing Tumors by Strengthening the Body Resistance） in combination with chemotherapeutics on human gastric carcinoma cell strain. METHODS： Fuzheng Yiliuyin （ZY） combined with various kinds of chemotherapeutics was put into two kinds of cultivated human gastric carcinoma cell strains, then its inhibitory effects on human gastric carcinoma cell strains were determind by the MTT method. Flow cytorneter was used to assay the apoptosis rate, and the ultrastructure of gastric carcinoma cells was observed under transmission electron microscope. RESULTS： Obvious apoptosis was seen in gastric carcinoma cells after treatment with ZY for 72 h. ZY and chemical drugs had synergistic inhibition effects on the cultivated gastric carcinoma cells, but the effects were different on various cell strains. The inhibitory effects of ZY could be strengthened by cytotoxic action and apoptosis. ZY combined with tluorouracil, etoposide and cisplatin （EFP） chemotherapeutics had better inhibitory effects on SGC-7901, while ZY combined with EFP or with DDP chemotherapeutics had better inhibitory effects than other drugs on MGC-803. CONCLUSION： ZY induces apoptosis and inhibits the growth of gastric carcinoma cells. ZY has the synergistic function of chemotherapeutics.

INTERACTIONS BETWEEN THE HUMAN GASTRIC CARCINOMA CELL AND THE HUMAN VASCULAR ENDOTHELIAL CELL

Objective To definite the interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the establishment and maintenance of the tumor vascular system and the tumor hematogenous metastasis.Methods We prepared the conditioned mediums of each cell so as to study the effect of the conditioned medium on itself or others by MTT colorimetry. The comprehensive effect of interactions between two cells was determined by stratified transfilter co culture or direct contact co culture.Results The conditioned medium of human gastric carcinoma cell can stimulate the proliferation of the human vascular endothelial cell, but the CM of HVEC can inhibit the growth of HGCC. Both kinds of cells can inhibit the growth of itself. The ultimate comprehensive effect of the interactions between two kinds of cells was increase of total cell numbers.Conclusion There exist the complicated interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the tumor angiogenesis and the tumor hematogenous metastasis. The ultimate comprehensive effect of the interactions is increase of total cells numbers and tumor volume.

Growth-inhibiting and Apoptosis-inducing Effects of Tanshinone ⅡA on Human Gastric Carcinoma Cells

To explore the effects of Tanshinone Ⅱ A on the proliferation, apoptosis and gene expression of p53 and bcl-2 in human gastric carcinoma MKN-45 cells. Cell count and MTT assay were used to study the proliferation-inhibiting effect of Tanshinone Ⅱ A on MKN-45 cells. The effect of Tanshinone Ⅱ A on the cell cycle and apoptosis of MKN-45 cells were examined by propidium iodide （PI） staining and flow cytometry. Semi-quantitative RT-PCR was used to further verify the ex- pression of p53 and bcl-2 gene after exposure to Tanshinone Ⅱ A in MKN-45 cells. The results showed that Tanshinone Ⅱ A significantly inhibited the growth and proliferation of MKN-45 cells in a dose- and time-dependent manner （P〈0.05）. Tanshinone Ⅱ A arrested MKN-45 cells in G2/M phase which led to an obvious accumulation of G2/M phase cells while decreased number of Go/G1 phase cells. This resulted in apoptosis of MKN-45 cells and the apoptosis rate was as high as 43.91% after treatment with 2.0 lag/mL Tanshinone Ⅱ A for 96 h. It was also found that Tanshinone Ⅱ A up-regulated expression of p53 gene and down-regulated expression of bcl-2 gene. The cytostatic and antiproliferative effect of Tanshinone Ⅱ A makes it a promising anticancer agent for the treatment of gastric carcinoma.

Effects of Cyclin D1 Antisense Oligodeoxyneucleotides on the Growth and Expression of G_1 Phase Regulators in Gastric Carcinoma Cells

To investigate the effects of Cyclin D1 antisense oligodeoxyneucleotides (ASODN) on the growth, cell cycle progression and expression of G 1 phase regulators in human gastric carcinoma cell lines SGC7901 and HS746T, phosphorothioate modified Cyclin D1 ASODN were encapsulated by LipofectAMINE2000 and transfected into gastric carcinoma cells. Dose dependent inhibitory effects were induced by Cyclin D1 ASODN in two gastric carcinoma cell lines. Treatment of gastric carcinoma cells with 0.2 μmol/L Cyclin D1 ASODN for 24 h could significantly inhibit their growth in vitro and in vivo , reduce expression of Cyclin D1mRNA to 26.3 % (SGC7901) and 17.3 % (HS746T) respectively. The percentage of cells in G 0/G 1 phase was increased as revealed by flow cytometry. Immunohistochemical staining showed that the expression of p21 was increased and the expression of Cyclin D1 and pRb was decreased in the two cell lines; the expression of p27 was increased in HS746T, but unchanged in SGC7901. Cyclin D1 ASODN could inhibit the growth and the expression of Cyclin D1 mRNA in gastric carcinoma cells, influence the cell cycle and expression of its regulators.

c-Ha-ras and c-myc antisense oligodeoxynucleotides inhibit the proliferation and DNA synthesis in human gastric carcinoma cell lines

The effects of two antisense oligodeoxynucleotides on the expression of c-Ha-ras proto-oncogene and the growth of human gastric carcinoma cell lines were observed. Synthetic 15-mer directed at the region of the translational initiation site of c-Ha-ras proto-oncogene (ASO-r) greatly inhibited the proliferation (55. 61%,P<0. 05) and DNA synthesis (76. 79%,P<0. 05) of MGc-803 cell line. It also inhibited the proliferation (62. 02%,P<0. 05) and DNA synthesis (76. 78%, P<0. 05) of SGc-7901 cell line. A reduction in intracellular P21 ras protein levels in MGc-803 cell line was observed 6 h after the treatment with ASO-r and maintained over 12 h. Another synthetic 15-mer targeted against the initiation codon and downstream 4 codons of c-myc proto-oncogene (ASOm) inhibited only DNA synthesis of MGc-803 cell line (71. 37%, P<0. 05). The control 15-mer did not inhibit the expression of P21 protein and proliferation of these cell lines. These experiments seemed to provide evidence that ASO-r could be effective in inhibiting the expression of c-Ha-ras proto-oncogene and controlling the growth of human gastric carcinoma cells,and that the over-expression of c-Ha-ras proto-oncogene might mainly be associated with the malignant proliferation of human gastric carcinoma cells.

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Gastric signet-ring cell carcinoma(GSRCC)is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis.Studies have shown that early GSRCC has a good prognosis,while advanced GSRCC is insensitive to radiotherapy,chemotherapy or immune checkpoint blockade therapy.With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry,more detailed atlas of tumor microenvironment(TME)in GSRCC and its association with prognosis could be investigated extensively.Recently,two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME,manifested as highly immunosuppressive,leading to high immune escape.The TME of advanced GSRCC was enriched for immunosuppressive factors,including the loss of CXCL13+-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells.In addition,GSRCC was mainly infiltrated by follicular B cells.The increased proportion of SRCC was accompanied by a decrease in mucosaassociated lymphoid tissue-derived B cells and a significant increase in follicular B cells,which may be one of the reasons for the poor prognosis of GSRCC.By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism,more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review

Gastric signet-ring cell gastric carcinoma(GSRC)is an unfavorable subtype of gastric cancer(GC)that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC.However,GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC.Therefore,the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients.In recent years,technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients.Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection(ESD),indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation.This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

Paris Saponin Ⅰ Induces G_2/M Cell Cycle Arrest and Apoptosis in Human Gastric Carcinoma SGC7901 Cells

The aim of this study was to investigate the effect of Paris saponin I （PSI ） on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms. The proliferation of SGC7901 cells was monitored by the MTT cell viability assay, while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining. Flow cytometry was performed to analyze the cell cycle progression of propidium iodide （PI）-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained ceils. Western blotting was used to examine the expression of several cell cycle proteins, including cyclin 131 and Cdkl, and the apoptosis-regulated proteins Bcl-2, Bax, cytochrome c, procaspase-9, and procaspase-3. The MTT assay demonstrated that PSI could induce significant dose- and time-dependent inhibition of SGC7901 cell proliferation. Marked morphological changes, including condensation of chromatin, nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining. PS I treatment also resulted in the disruption of the cell cycle at Gz/M and the induction of apoptosis. Following PSI treatment, the cell cycle-related proteins cyclin B 1 and Cdkl were down- regulated. Expression of the pro-apoptotic protein Bax was increased, while anti-apoptotic protein Bcl-2 decreased. PSI treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3. These data indicate that PS I acts as an inhibitor of proliferation in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis. PSI is a potential therapeutic agent against human gastric carcinoma.

Poorly cohesive cells gastric carcinoma including signet-ring cell cancer:Updated review of definition,classification and therapeutic management

While the incidence of gastric cancer(GC)in general has decreased worldwide in recent decades,the incidence of diffuse cancer historically comprising poorly cohesive cells-GC(PCC-GC)and including signet ring cell cancer is rising.Literature concerning PCC-GC is scarce and unclear,mostly due to a large variety of historically used definitions and classifications.Compared to other histological subtypes of GC,PCC-GC is nevertheless characterized by a distinct set of epidemiological,histological and clinical features which require a specific diagnostic and therapeutic approach.The aim of this review was to provide an update on the definition,classification and therapeutic strategies of PCC-GC.We focus on the updated histological definition of PCC-GC,along with its implications on future treatment strategies and study design.Also,specific considerations in the diagnostic management are discussed.Finally,the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens(5-Fluorouracil,leucovorin,oxaliplatin and docetaxel),the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

Clinicopathological characteristics and prognosis of gastric signet ring cell carcinoma

BACKGROUND The clinicopathological features and prognosis of gastric signet ring cell carcinoma(GSRC)remain controversial,particularly with regard to sensitivity to postoperative adjuvant therapy.AIM To compare the pathological features of GSRC with those of gastric adenocarcinoma of different degrees of differentiation and the differences in survival prognosis between the different disease processes.METHODS By screening gastric cancer patients from 2010 to 2015 in the database of Surveillance,Epidemiology and End Results,and collecting the clinicopathological and prognostic data of gastric cancer patients who underwent surgery from January 2014 to December 2016 in the Second Affiliated Hospital of Nanchang University,we analyzed the general pathological characteristics of GSRC by the chi-square test.Univariate and multivariate analyses were conducted to compare the factors affecting the survival and prognosis of early and advanced gastric adenocarcinoma.The Kaplan-Meier curves were plotted to reveal the survival difference between early and advanced GSRC and different differentiated types of gastric adenocarcinoma.The prognosis model of advanced GSRC was established with R software,and the area under curve(AUC)and C-index were used to assess the accuracy of the model.RESULTS Analysis of pathological features revealed that signet ring-cell carcinoma(SRC)was more frequently seen in younger(<60 years),female,and White patients compared to non-SRC patients.SRC was less commonly associated with early gastric cancer(EGC)(23.60%vs 39.10%),lower N0(38.61%vs 61.03%),and larger tumour sizes>5 cm(31.15%vs 27.10%)compared to the differentiated type,while the opposite was true compared to the undifferentiated type.Survival prognostic analysis found no significant difference in the prognosis of SRC patients among EGC patients.In contrast,among advanced gastric cancer(AGC)patients,the prognosis of SRC patients was correlated with age,race,tumour size,AJCC stage,T-stage,and postoperative adjuvant therapy.The predictive model showed that the 3-year AUC was 0.787,5-year AUC was 0.806,and C-index was 0.766.Compared to non-SRC patients,patients with SRC had a better prognosis in EGC[hazard ratio(HR):0.626,95%confidence interval(CI):0.427-0.919,P<0.05]and a worse prognosis in AGC(HR:1.139,95%CI:1.030-1.258,P<0.05).When non-SRC was divided into differentiated and undifferentiated types for comparison,it was found that in EGC,SRC had a better prognosis than differentiated and undifferentiated types,while there was no significant difference between differentiated and undifferentiated types.In AGC,there was no significant difference in prognosis between SRC and undifferentiated types,both of which were worse than differentiated types.A prognostic analysis of postoperative adjuvant therapy for SRC in patients with AGC revealed that adjuvant postoperative radiotherapy or chemotherapy significantly improved patient survival(34.6%and 36.2%vs 18.6%,P<0.05).CONCLUSION The prognosis of SRC is better than that of undifferentiated type,especially in EGC,and its prognosis is even better than that of differentiated type.SRC patients can benefit from early detection,surgical resection,and aggressive adjuvant therapy.

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Objective： To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma （MGC） and signet-ring cell carcinoma （SRCC）. Methods： Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using Z2 test. Survival was analyzed using the Kaplan- Meier method and multivariate analysis of Cox proportional hazards regression model （backward, stepwise）. Results： A total of 181 patients with gastric cancer （74 MGC, 107 SRCC） were included. MGC, when compared with SRCC, was featured by senile patients, stage III and I~, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion （P〈0.05）. The overall 5-year survival rate showed no difference between the two groups （48.8% vs. 44.8%, P〉0.05）. However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age 〈60 years, negative distant metastasis, and tumor localized at upper third stomach （P〈0.05）. Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions： While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.

The Relationship between Apoptosis and the Expression of Proliferating Cell Nuclear Antigen and the Clinical Stages in Gastric Carcinoma

The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase mediated nick end labelling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5±3.7) % and (49.8±15.9) % respectively, and the rate of AI/PI was 0.13±0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer ( P <0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage Ⅱ to Ⅳ ( P <0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.

Surgically resected gastric metastasis of pulmonary squamous cell carcinoma

Gastric metastasis of pulmonary carcinoma has been reported to range from 0.19%-5.1%.An autopsy review of cancer disclosed 1.7%-29.6%of gastric metastases,primarily from breast cancer,lung cancer and melanoma.A 71-year-old man was referred to our department because of persistent cough,sputum and sweating for 20 d.Chest posteroanterior view and chest computed tomography scan demonstrated an irregular tumor mass measuring 5.8 cm with central necrosis at the right lower lung.Bronchoscopic biopsy revealed pulmonary squamous carcinoma.Esophagogastroduodenoscopy revealed a huge bleeding ulcer at the body of the stomach and a biopsy diagnosed a metastatic lesion.We performed a palliative total gastrectomy,splenectomy and distal pancreatectomy.The patient did not receive any adjuvant chemotherapy due to his refusal.He was controlled conservatively and survived for 11 mo after surgery.Surgical resection may provide an option for safe palliative treatment.Although gastric metastasis from lung cancer is associated with dismal outcomes,a longer survival or more favorable outcome has been demonstrated in patients undergoing palliative surgical resection of the metastatic site.Considerable improvements in the understanding of metastatic diseases and therapeutic strategies are needed to improve the clinical outcome.

Primary gastric signet ring cell carcinoma presenting as cardiac tamponade

Primary gastric signet ring cell carcinoma presenting as cardiac tamponade is difficult to diagnosis early. Patients are generally asymptomatic until the disease is advanced. General practitioners usually focus on the initial symptoms related to pericarditis and pericardial effusion. We report a case of signet-ring cell carcinoma of the stomach presenting as cardiac tamponade with pericarditis and pericardial effusion but without any gastrointestinal symptoms. A 49-year old woman was admitted because of progressive dyspnea and cough. Chest X-ray revealed an increased cardiothoracic ratio and a small amount of bilateral pleural effusion. Two dimensional ultrasonographic echocardiography pericardial effusions with atrial and right ventricular early diastolic collapse were found, establishing the diagnosis of cardiac tamponade. Pericardiocentesis was performed and 420 mL of bloody ?uid was taken. The patient died of respiratory failure and cardiac arrest on October 28, 2009. Post-mortem examination revealed diffuse gastric mucosa erosion and edema with stomach mucosa incrassation in the greater curvature. The primary lesion was histopathologically diagnosed as signet-ring cell carcinoma of the stomach.

STUDY ON PROLIFERATIVE ACTIVITY OF ENDOCRINE CELLS IN GASTRIC CARCINOMA

Endocrine cell(EC) in 11 cases picked up from 56 cases of gastric carcinoma were observed by double immunohistochemical method using chromogramnin A(CgA) and proliferating cell nuclear antigen(PCNA).The endocrine cells were recognized by a antibody to CgA and the proliferative activity by a monoclonal antibody to PCNA.11 cases CgA positive GC cells with PCNA incorporation was in 51/4069(0-3%) with an average 1.25%.By contrast PCNA reaction was positive in 31.9±14.7% of CgA negative GC cells.It suggests that there were a few cell in S and G1 phase and most of them in G0 phase.

INDUCTION OF APOPTOSIS IN HUMAN GASTRIC CARCINOMA CELL LINE MGC-803 BY MONOCLONAL ANTIBODY PD4

Objective: To study the effect of McAb PD4 on the cell cycle and on cell injury in the gastric carcinoma cell line, MGC 803. Methods: The effects of McAb PD4 on cell proliferation cycle and cell injury of MGC 803 cells were examined by flow cytometry analysis, DNA electrophoresis and terminal deoxynucle otidyl trans ferase assay. Fas antigen was investigated by ELISA. Results: McAb PD4 inhibited tumor growth of MGC 803 cells in nude mice by inducing apoptosis. Conclusion: P40 is a tumor associated antigen distinct from the Fas antigen. Molecular cloning of P40 will define the pathway and mechanism of apoptosis induced by McAb PD4. Induction of apoptosis by McAb PD4 may be a useful therapeutic approach in treating cancer.

Identification of key genes and pathways in gastric signet ring cell carcinoma based on transcriptome analysis

BACKGROUND Gastric signet ring cell carcinoma(GSRCC)is one of the most malignant tumors.It has the features of high invasiveness,rapid progression,and resistance to chemotherapy.However,systematic analyses of mRNAs have not yet been performed for GSRCC.AIM To identify key mRNAs and signaling pathways in GSRCC.METHODS A transcriptome analysis of two GSRCC and two non-GSRCC samples was performed in this study.Differentially expressed mRNAs and pathways were identified based on the KEGG and PANTHER pathway annotations.The interactive relationships among the differential genes were mapped with the STRING database.Quantitative real-time polymerase chain reaction was used to validate the key gene expression in GSRCC.RESULTS About 1162 differential genes(using a 2-fold cutoff,P<0.05)were identified in GSRCC compared with non-GSRCC.The enriched KEGG and PANTHER pathways for the differential genes included immune response pathways,metabolic pathways,and metastasis-associated pathways.Ten genes(MAGEA2,MAGEA2B,MAGEA3,MAGEA4,MAGEA6,MUC13,GUCA2A,FFAR4,REG1A,and REG1B)were identified as hub genes in the protein-protein interaction network.The expression levels of five genes(MAGEA2,MAGEA3,MAGEA4,MAGEA6,and REG1B)showed potential clinical value.CONCLUSION We have identified the potential key genes and pathways in GSRCC,and these hub genes and pathways could be diagnostic markers and therapeutic targets for GSRCC.