Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,respectively.However,the clinical importance of the special combined AB and PAS stain is unclear.AIM To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient prognosis.METHODS Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed quantitatively.Immuno-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed simultaneously.The cancer-specific survival(CSS)rate was estimated via Kaplan-Meier analysis.Cox proportional hazards models were used for univariate and multivariate survival analyses.RESULTS Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P<0.001).The 3-year CSS rate in the A/P≤0.5 group was significantly greater than that in the A/P>0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the PAS.Cox multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor prognosis.CONCLUSION A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric SRCC.PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma:A real-world retrospective cohort study

BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to pathological type.We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis(LNM).AIM To establish models to predict LNM in early GC(EGC),including early gastric SRCC.METHODS Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed.The patients were divided into three groups based on type:Pure SRCC,mixed SRCC,and non-signet ring cell carcinoma(NSRC).The risk factors were identified through statistical tests using SPSS 23.0,R,and EmpowerStats software.RESULTS A total of 1922 subjects with EGC were enrolled in this study,and included 249 SRCC patients and 1673 NSRC patients,while 278 of the patients(14.46%)presented with LNM.Multivariable analysis showed that gender,tumor size,depth of invasion,lymphovascular invasion,ulceration,and histological subtype were independent risk factors for LNM in EGC.Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy(98.0%vs 58.1%,P=0.034;88.4%vs 86.8%,P<0.001,respectively).Among the 249 SRCC patients,LNM was more common in mixed(35.06%)rather than in pure SRCC(8.42%,P<0.001).The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760(95%CI:0.682-0.843),while the area under the operating characteristic curve of the internal validation set was 0.734(95%CI:0.643-0.826).The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size>2 cm(OR=5.422,P=0.038).CONCLUSION A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC,which can aid in pre-surgical decision making of the best method of treatment for patients.

MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the MAPK pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis

BACKGROUND Gastric carcinoma(GC)is the third most frequent cause of cancer-related death,highlighting the pressing need for novel clinical treatment options.In this regard,microRNAs(miRNAs)have emerged as a promising therapeutic strategy.Studies have shown that miRNAs can regulate related signaling pathways,acting as tumor suppressors or tumor promoters.AIM To explore the effect of miR-204-3p on GC cells.METHODS We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction,followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC cells.CCK-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells,and the colony formation ability of GC cells was detected by the clonal formation assay.The effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow cytometry.The BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC cells.Furthermore,the study investigated the effects of miR-204-3p on various proteins related to the MAPK signaling pathway,necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot techniques.RESULTS Firstly,we found that the expression of miR-204-3p in GC was low.When treated with the lentivirus overexpression vector,miR-204-3p expression significantly increased,but the lentivirus knockout vector had no significant effect on miR-204-3p.In vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability,promoted cell apoptosis,blocked the cell cycle,and inhibited colony formation ability.In vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude mice.Simultaneously,our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the MAPK pathway,as well as inhibiting protein expression levels of p-RIP1 and p-MLK1 in the necroptosis pathway to promote the BCL-2/BAX/Caspase-3 apoptosis pathway.CONCLUSION MiR-204-3p overexpression inhibited GC cell proliferation by inhibiting the MAPK pathway and necroptosis pathway to promote apoptosis of GC cells.Thus,miR-204-3p may represent a new potential therapeutic target for GC.

Down-regulated expressions of PPAR_γ and its coactivator PGC-1 are related to gastric carcinogenesis and Lauren's classification in gastric carcinoma

Objective： To explore the relationship between peroxisome proliferator activated receptor-gamma （PPARγ） and peroxisome proliferator-activated receptor-gamma coactivator-1 （PGC-1） expression in gastric carcinoma （GC）, and analyze their correlations with clinicopathological features and clinical outcomes of patients. Methods：The two-step immunohistochemical method was used to detect the expression of PPARγ and PGC-1 in 179 cases of GC, and 108 cases of matched normal gastric mucosa. Besides, 16 cases of fresh GC specimens and corresponding normal gastric mucosa were detected for PGC-1 expression with Western blotting. Results： The positive rates of PPART and PGC-1 expression were significantly lower in GC （54.75%, 49.16%） than in normal gastric mucosa （70.37%, 71.30%）, respectively （P〈0.05）. The decreased expression of PGC-1 in GC was confirmed ha our Western blot analysis （P=0.004）. PPAR7 and PGC-1 expressions were related to Lauren＇s types ofGC （P〈0.05）. Positive correlation was found between PPART and PGC-1 expression in GC （rk=0.422, P〈0.001）. The survival time of PPART negative and positive patients was 36.6±3.0 vs. 38.5_＋2.7 months, and no statistical difference was found between the 5-year survival rates of two groups （34.4% vs. 44.1%, P=0.522, log-rank test）; the survival time of PGC-1 negative and positive patients was 36.2±2.8 vs. 39.9±2.9 months, while no statistical difference was found between the 5-year survival rates of the two groups （32.0% vs. 48.2%, P=0.462, log-rank test） Conclusions＇. Decreased expression of PPARγand PGC-1 in GC was related to the Lauren＇s classification. Their expressions in GC were positively correlated, indicating that their fimctions in gastric carcinogenesis may be closely related.

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.

Appraisal of gastric stump carcinoma and current state of affairs

Gastric stump carcinoma,also known as remnant gastric carcinoma,is a malignancy arising in the remnant stomach following gastrectomy for a benign or malignant condition.Enterogastric reflux and preexisting risk factors in a patient with gastric cancer are the major contributors to the development of gastric stump carcinoma.The occurrence of gastric stump carcinoma is time-dependent and seen earlier in patients operated on for malignant rather than benign diseases.The tumor location is predominantly at the anastomotic site towards the stomach.However,it can occur anywhere in the remnant stomach.The pattern of lymph node involvement and the type of surgery required is distinctly different compared to primary gastric cancer.Gastric stump carcinoma is traditionally considered a malignancy with a dismal outcome.However,recent advances in diagnostic and therapeutic strategies have improved outcomes.Recent advances in molecular profiling of gastric stump carcinoma have identified distinct molecular subtypes,thereby providing novel therapeutic targets.Also,reports of gastric stump carcinoma following pancreatoduodenectomy and bariatric surgery highlight the need for more research to standardize the diagnosis,staging,and treatment of these tumors.The present review aims to provide an overview of gastric stump carcinoma highlighting the differences in clinicopathological profile and management compared to primary gastric carcinoma.

Deltonin enhances gastric carcinoma cell apoptosis and chemosensitivity to cisplatin via inhibiting PI3K/AKT/mTOR and MAPK signaling

BACKGROUND As an active ingredient derived from Dioscorea zingiberensis C.H.Wright,deltonin has been reported to show anti-cancer effects in a variety of malignancies.AIM To investigate the role and mechanism of action of deltonin in promoting gastric carcinoma(GC)cell apoptosis and chemosensitivity to cisplatin.METHODS The GC cell lines AGS,HGC-27,and MKN-45 were treated with deltonin and then subjected to flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltet-razolium bromide assays for cell apoptosis and viability determination.Western blot analysis was conducted to examine alterations in the expression of apoptosis-related proteins(Bax,Bid,Bad,and Fas),DNA repair-associated proteins(Rad51 and MDM2),and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin(PI3K/AKT/mTOR)and p38-mitogen-activated protein kinase(MAPK)axis proteins.Additionally,the influence of deltonin on GC cell chemosensitivity to cisplatin was evaluated both in vitro and in vivo.RESULTS Deltonin treatment weakened viability,enhanced apoptosis,and dampened DNA repair in GC cell lines in a dose-dependent pattern.Furthermore,deltonin mitigated PI3K,AKT,mTOR,and p38-MAPK phosphorylation.HS-173,an inhibitor of PI3K,attenuated GC cell viability and abolished deltonin inhibition of GC cell viability and PI3K/AKT/mTOR and p38-MAPK pathway activation.Deltonin also promoted the chemosensitivity of GC cells to cisplatin via repressing GC cell proliferation and growth and accelerating apoptosis.CONCLUSION Deltonin can boost the chemosensitivity of GC cells to cisplatin via inactivating p38-MAPK and PI3K/AKT/mTOR signaling.

Gastric adenosquamous carcinoma with an elevated serum level of alpha-fetoprotein:A case report

BACKGROUND Gastric adenosquamous carcinoma(ASC)is rare and characterized by coexisting of adenocarcinoma andsquamous carcinoma within the same tumor.We present a female patient with gastric ASC who had an elevated serum level of alpha-fetopro-tein(AFP),which decreased to normal levels after a laparoscopic distant radical gastrectomy in a short period.The clinicopathological features in AFP-producing gastric cancer(GC)are discussed,as well as potentially available prognostic predi-ctors.CASE SUMMARY A 50-year-old woman presented to our department with a chief complain of a 6-mo history of bloating.She had no basic diseases including heart diseases and respiratory diseases,and she also denied any prior history of dysphagia,hematemesis,melena,rectal bleeding,hematochezia,or unintentional weight loss.Based on her symptoms,an esophagogastroduodenoscopy was performed,showing an annular cavity lesion 3 cm from the pylorus with a diameter of 6 cm.A biopsy of the lesion showed gastric ASC,whereas the pylorus biopsy showed normal mucosa.The patient further received an enhanced computed tomography scan which demonstrated an invasive lesion close to the pylorus with a still clear margin of the tumor to peripheral organs such as the pancreas and liver.Scattered lymph nodes were visible around,whereas no sign of liver metastasis was discovered.Serum tumor markers including carcinoembryonic antigen(CEA),cancer antigen 199(CA199),CA724,CA125,and CA242 were all normal,while the level of serum AFP increased to 172 ng/mL.A laparoscopic distant radical gastrectomy was performed after exclusion of surgical contraindications.Postoperative pathology results showed that the tumor displayed an ulcerated ASC phenotype(90%of medium to highly-differentiated squamous cell carcinoma,10%of poorly differentiated adenocarcinoma.Surprisingly,the serum level of AFP decreased to normal level on post operation day 5.The tumor cells were positive for CK5/6,p63,and CEA,and negative for AFP and Epstein-Barr encoding region.CONCLUSION We presented a rare case of gastric ASC with elevated serum AFP level,which may be new subtype of AFP-producing GC.Follow-up detection of serum AFP might be a useful tool to predict patient prognosis.

Quantitative parameters in novel spectral computed tomography:Assessment of Ki-67 expression in patients with gastric adenocarcinoma

BACKGROUND The level of Ki-67 expression has served as a prognostic factor in gastric cancer.The quantitative parameters based on the novel dual-layer spectral detector computed tomography(DLSDCT)in discriminating the Ki-67 expression status are unclear.AIM To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma(GC).METHODS Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma.Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt(kev),the slope of the spectral curve(λ_(HU)),iodine concentration(IC),normalized IC(nIC),effective atomic number(Z^(eff))and normalized Z^(eff)(nZ^(eff))in the arterial phase(AP)and venous phase(VP)were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma.Spearman’s correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status.Receiver operating characteristic(ROC)curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups.RESULTS Thirty-seven and 71 patients were classified as having low and high Ki-67 expression,respectively.CT_(40 kev-VP),CT_(70 kev-VP),CT_(100 kev-VP),and Z^(eff)-related parameters were significantly higher,but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status,and other analyzed parameters showed no statistical difference between the two groups.Spearman’s correlation analysis showed that CT_(40 kev-VP),CT_(70 kev-VP),CT_(100 kev-VP),Z^(eff),and n Z^(eff) exhibited a negative correlation with Ki-67 status,whereas IC and nIC had positive correlation with Ki-67 status.The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status[area under the curve(AUC)=0.967;sensitivity 95.77%;specificity 91.89%)].Nevertheless,the differentiating capabilities of singlevariable model were moderate(AUC value 0.630-0.835).In addition,the nZ_(VP)^(eff) and nIC_(VP)(AUC 0.835 and 0.805)showed better performance than CT_(40 kev-VP),CT_(70 kev-VP) and CT_(100 kev-VP)(AUC 0.630,0.631 and 0.662)in discriminating the Ki-67 status.CONCLUSION Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma.Z^(eff) and IC may be useful parameters for evaluating the Ki-67 expression.

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.

In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells

AIM: To investigate the effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 in vitro and the possible mechanisms involved.METHODS: Chitosan nanoparticles were characterized by particle size, zeta potential, and morphology. After treatment with various concentrations of chitosan nanoparticles (25, 50, 75, 100 μg/mL) at various time intervals, cell proliferation, ultrastructural changes, DNA fragmentation, mitochondrial membrane potential (MMP),cell cycle phase distribution and apoptotic peaks of MGC803 cells were analyzed by MTT assay, electron microscopy,DNA agarose gel electrophoresis, and flow cytometry.RESULTS: Chitosan nanoparticles exhibited a small particle size as 65 nm and a high surface charge as 52 mV.Chitosan nanoparticles markedly inhibited cell proliferation of MGC803 cells with an IC50 value of 5.3 μg/mL 48 h after treatment. After treatment with chitosan nanoparticles,the typical necrotic cell morphology was observed by electron microscopy, a typical DNA degradation associated with necrosis was determined by DNA agarose electrophoresis.Flow cytometry showed the loss of MMP and occurrence of apoptosis in chitosan nanoparticles-treated cells.CONCLUSION: Chitosan nanoparticles effectively inhibit the proliferation of human gastric carcinoma cell line MGC803 in vitro through multiple mechanisms, and may be a beneficial agent against human carcinoma.

Massive bleeding from a gastric artery pseudoaneurysm in hepatocellular carcinoma treated with atezolizumab plus bevacizumab: A case report

BACKGROUND The combination of atezolizumab(ATZ)and bevacizumab(BVZ)was approved as first-line systemic therapy for advanced hepatocellular carcinoma(HCC)owing to its superior rates of response and patient survival.However,ATZ+BVZ is associated with increased risk of upper gastrointestinal(GI)bleeding,including arterial bleeding,which is rare and potentially fatal.We present a case of massive upper GI bleeding from a gastric pseudoaneurysm in a patient with advanced HCC who had been treated with ATZ+BVZ.CASE SUMMARY A 67-year-old man presented with severe upper GI bleeding after atezolizumab(ATZ)+bevacizumab(BVZ)therapy for HCC.Endoscopy failed to detect the bleeding site.Digital subtraction angiography revealed a gastric artery pseudoaneurysm and contrast extravasation from the inferior splenic artery and a branch of the left gastric artery.Successful hemostasis was achieved with embolization.CONCLUSION HCC patients who have been treated with ATZ+BVZ should be followed for 3 to 6 mo to monitor for development of massive GI bleeding.Diagnosis may require angiography.Embolization is an effective treatment.

Inhibitory effects of apigenin on the growth of gastric carcinoma SGC-7901 cells

AIM: To explore the growth inhibition and apoptosisinducing effect of apigenin on human gastric carcinoma SGC-7901 cells.METHODS: The effects of apigenin on the growth, clone formation and proliferation of human gastric carcinoma SGC-7901 cells were observed by MTT, clone-forming assay,and morphological observation. Fluorescent staining and flow cytometry analysis were used to detect apoptosis of cells.RESULTS: Apigenin obviously inhibited the growth, clone formation and proliferation of SGC-7901 cells in a dosedependent manner. Inhibition of growth was observed on d 1 at the concentration of 80 μmol/L, while after 4 d,the inhibition rate (IR) was 90%. The growth IRs at the concentration of 20, 40, and 80 μmol/L were 38%, 71%,and 99% respectively on the 7th d. After the cells were treated with apigenin for 48 h, the number of clone-forming in control,20, 40, and 80 μmol/L groups was 217±16.9, 170±11.1(P＜0.05), 98±11.1 (P＜0.05), and 25±3.5 (P＜0.05)respectively. Typical morphological changes of apoptosis was found by fluorescent staining. The cell nuclei had lost its smooth boundaries, chromatin was condensed, and cell nuclei were broken. Flow cytometry detected typical apoptosis peak. After the cells were treated with apigenin for 48 h, the apoptosis rates were 5.76%, 19.17%, and 29.30% respectively in 20, 40, and 80 μmol/L groups.CONCLUSION: Apigenin shows obvious inhibition on the growth and clone formation of SGC-7901 cells by inducing apoptosis.

Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human gastric carcinoma cell line BGC-823

AIM: To investigate the co-expression and significance of heat shock protein 70 (HSP70) and glucose-regulatedprotein 94 (grp94) in human gastric carcinoma cell line BGC-823.METHODS: The expression and localization of HSP70 and grp94 in human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry and indirect immunofiuorescence cytochemical staining. Flow cytometry was used to analyze the correlation between expression of HSP70, grpg4 and cell cycle in BGC-823 cell line.RESULTS: Gastric cancer cell line BGC-823 expressed high level of HSP70 and grp94. The positive rate of HSP70 and grp94 was 84.9±4.94% and 79.6±5.16%, respectively. Bothof them were stained in cell plasma. There was a significant difference compared with control group (1.9±0.94%,P＜0.01). During the cell cycle, HSP70 and grp94 were continuously expressed in BGC-823.CONCLUSION: HSP70 and grp94 are highly expressed in human gastric carcinoma BGC-823 cells through the whole cell cycle. There is no relationship between expression of HSP70, grp94 and cell cycle.

Genomic characterization of peritoneal lavage cytology-positive gastric cancer

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review

BACKGROUND Upper gastrointestinal(GI)signet ring cell carcinomas(SRCC)confer a poor prognosis.The benefit of operative intervention for this patient group is contro-versial in terms of overall survival.AIM To investigate factors relating to survival in patients with upper GI SRCC.METHODS A retrospective,tertiary,single-centre review of patients who were diagnosed with oesophageal,gastroesophageal junction and gastric SRCC was performed.The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management.Secon-dary outcomes included assessing the relationship between demographic and histopathological factors,and survival.RESULTS One hundred and thirty-one patients were included.The one-year survival for the operative group was 81%and for the nonoperative group was 19.1%.The five-year survival in the operative group was 28.6%vs 1.5%in the nonoperative group.The difference in overall survival between groups was statistically significant(HR 0.19,95%CI(0.13-0.30),P<0.001).There was no difference in survival when ad-justing for age,smoking status or gender.On multivariate analysis,patients who underwent surgical management,those with a lower stage of disease,and those with a lower Charlson Comorbidity Index(CCI)had significantly improved sur-vival.CONCLUSION Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery.Offering surgery to a carefully selected patient group may improve the outcome for this disease.

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.

Combined therapeutic effects of cytotoxic agent and differentiation-inducer on human gastric carcinoma cell line SGC-7901

Objective:To study the combined therapeutic effects of cytotoxic agent and differentiation-inducer on human gas tric carcinoma celll line SGC-7901 in vitro. Methods: The combined therapeutic effects of all-trans retinoic acid (ATRA), interferon a (IFNa)and fluorouracil (5-Fu) on gastric carcinoma cell line ax 7901 were observed when one of the 3, the combination of any 2 of the 3 and combination of all the 3 were administered respectively. The morphological and functional changes of gastric carcinoma cells were studied with MTT assay, flow cytometry, image analysis and determination of CEA content in the culture medium of the cells. Results: The cytostatic rate was increased as shown by the decrease of the rate of colony formation of the cells on culture disc when one agent, the combination of 2 agents and the combination of the 3 were administered progressively. The cells were relatively accumulated in the phase of G0/G1 and synthesis of DNA in he cells was inhibited.The malignant phenotype of the cells disappeared gradually while the characteristics of matUre cells were in creased. Meanwhile, CEA Level in the culture medium was decreased progressively. Apoptosis of the cells was oborved and a large amount of apoptotic apoptotic were found. Conclusion: The administration of the 3 agents in combination result in signif icant inhibition on proliferation, inducing of differention and promotion of apoptosis of gastric caxcinoma cells. The combina tion of cytotoxic agent and differention-inducer exerts significant inhibition on gastric carcinoma cells in vitro.

Effect of antisense human telomerase RNA on malignant behaviors of gastric carcinoma cell line SGC-7901

Objective:To studytheeffectsof antisensehumantelomeraseRNA(ahTR)transfectionon themalignantbeha-viorsof gastriccarcinomacelllineSGC-7901anditspotentialroleingenetherapyfortumor.Methods:AnantisensehTR eukaryoticexpressionvectorcontainingthesequenceof templateregionof telomererepeatswas transfectedintogastric carcinomacelllineSGC-7901withliposomeDOTAP.Theexpressionsof hTRRNAandantisensehTRRNAwereob-servedwithRT-PCR,telomeraseactivitywithPCR-ELISA.Telomerelengthwas measuredwithSouthernblot.Cellmor-phologyandcellularproliferationcapacitywerestudiedwithMTTassay.Cellcycledistributionandapoptoticstatewere observedwithflowcytometry.Efficiencyof cloneformationin softagarandtumorigencityin nudemicewereexamined andevaluatedinahTR-transfected7901cells,andplasmidpCL-neotransfected7901cellsandparental7901cellsserved as control.Results:AnantisensehTReukaryoticexpressionvectorwastransfectedinto7901cellssuccessfully.Thetelom-eraseactivityin ahTR-transfected7901cellswas decreasedfrom100%to about25%,andtelomerelengthin thecells shortenedfrom4.08kb to3.35kb at60populationdoublings(PDs).Comparedwithparental7901andpCL-neotransfect-ed7901cells,ahTR-transfected7901cellsdisplayedsomemorphologicalchanges,includingdecreasedcellatypiaandnu-cleus/cytoplasmratiounderlightmicroscope.Furthermore,ahTR-transfected7901cellsdisplayedgrowthinhibition,de-creasedinvasivecapacityin Borden’schamberinvasivemodel,increasedG 0 /G 1 phaserateandapoptoticrate,andrestored contactinhibitionanddensityinhibition.Surprisingly,ahTR-transfected7901cellslosttheircapacityof cloneformationin softagarandcarcinogensisinnudemice.Conclusion:AntisensehTRtransfectioncaninduce7901celldifferentiationand reverseitsmalignantphenotype.Thisstudyprovidesan excitingapproachfor cancertherapythroughtheinhibitionof telomeraseactivitywithantisensegeneandothertelomeraseinhibitors.

贝伐珠单抗与GC化疗方案联合治疗晚期非小细胞肺癌的效果及药物经济学评价

目的 探究贝伐珠单抗联合GC化疗方案(顺铂+吉西他滨)治疗晚期非小细胞肺癌(NSCLC)的效果及药物经济学价值。方法 选取2020年7月—2022年7月收治的86例晚期NSCLC,依据治疗方案分为对照组和观察组,每组43例。对照组给予GC化疗方案,观察组给予贝伐珠单抗联合GC化疗方案。对比2组疗效、毒副反应发生情况以及治疗前后血生化指标,并进行成本-效果分析。结果 观察组客观缓解率58.14%(25/43)、疾病控制率93.02%(40/43)均高于对照组的32.56%(14/43)、72.09%(31/43)(P<0.05)。治疗2、4个疗程,观察组血清癌胚抗原、糖类抗原125、神经元特异性烯醇化酶、血管内皮生长因子、碱性成纤维细胞生长因子均低于对照组(P<0.05)。2组各项毒副反应总发生率比较无显著差异(P>0.05)。观察组总成本高于对照组(P<0.05)。观察组成本-效果比为790.67低于对照组的901.31,且敏感性分析显示,成本-效果分析稳定可靠。结论 贝伐珠单抗联合GC化疗方案治疗晚期NSCLC患者,可下调肿瘤标志物及血管内皮因子水平,提升疗效,且成本-效果优势明显。