Dual primary gastric and colorectal cancer:The known hereditary causes and underlying mechanisms

In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1-extracellular signal-regulated kinase-1/2 axis

BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Familial gastric cancers with Li-Fraumeni Syndrome: A case repast

TO THE EDITORAlthough the incidence of gastric cancer has declined somewhat in recent years, it remains one of the most common cancers worldwide[1], and is the most common cancer in East Asian countries such as Korea and Japan[2].In terms of the genetics of gastric cancer, mutations in CDH1 (E-cadberin) have been associated with hereditary diffuse gastric cancer (HDGC). The first germline mutation in CDH1 was reported in a large Maori HDGC family[1],with subsequent corroborations in Western and Asian HDGC families[3-5], CDH1 mutations are believed to be associated with up to 50% of HDGC families[5], but have not been linked with sporadic or intestinal types of gastric cancer[5].

Family history of cancer in Chinese gastric cancer patients

Objective:The aim of the study was to investigate the influence of gastric cancer family history in the gastric cancer (GC) patients. Methods: Gastric cancer family histories within second degree relatives and clinicopathological features were obtained for 497 patients. Results:Of the 497 probands,235 probands were incorporated into familial gastric cancer (FGC) group (there were at least two GC members in the family); 262 probands were included in the non-FGC group (relatives only affected with non-GCs). Of 614 tumors in relatives,GC was the most frequent,followed by lung cancer,esophageal cancer,hepatocellular cancer,colorectal cancer,urogenital cancer,breast cancer,and pancreatic cancer. Most affected members aggregated within first-degree relatives. The ratio of males to females in affected first-degree relatives was usually higher in male probands. Paternal history of GC was a strong risk for GC in males,while risk of GC by maternal history of GCs was increased in females. Difference in tumor histological types between the two groups was derived from an excess of diffuse GC in non-FGC male probands. The lower site was the most frequent tumor location in all subgroups. Conclusion:Distribution of associated non-GCs in a family history of GC may vary with geographic areas. GC may have different genetic and/or environmental etiology in different families,and a certain subtype may be inherited in a male-influenced fashion.

Individual having a parent with early-onset gastric cancer may need screening at younger age

AIM: To evaluate whether individuals with gastric cancer(GC) are diagnosed earlier if they have firstdegree relatives with GC.METHODS: A total of 4282 patients diagnosed with GC at National Cancer Center Hospital from 2002 to 2012 were enrolled in this retrospective study. We classified the patients according to presence or absence of first-degree family history of GC and compared age at diagnosis and clinicopathologic characteristics. In addition, we further classified patients according to specific family member with GC(father, mother, sibling, or offspring) and compared age at GC diagnosis among these patient groups. Baseline characteristics were obtained from a prospectively collected database. Information about the family member's age at GC diagnosis was obtained by questionnaire.RESULTS: A total of 924 patients(21.6%) had a firstdegree family history of GC. The mean age at GC diagnosis in patients having paternal history of GC was 54.4 ± 10.4 years and was significantly younger than in those without a first-degree family history(58.1 ± 12.0 years, P < 0.001). However, this finding was not observed in patients who had an affected mother(57.2 ± 10.0 years) or sibling(62.2 ± 9.8 years). Among patients with family member having early-onset GC(< 50 years old), mean age at diagnosis was 47.7 ± 10.3 years for those with an affected father, 48.6 ± 10.4 years for those with an affected mother, and 57.4 ± 11.5 years for those with an affected sibling. Thus, patients with a parent diagnosed before 50 years of age developed GC 10.4 or 9.5 years earlier than individuals without a family history of GC(both P <0.001).CONCLUSION: Early-onset GC before age of 50 was associated with parental history of early-onset of GC. Individual having such family history need to start screening earlier.

What is the quantitative risk of gastric cancer in the first-degree relatives of patients? A meta-analysis

AIMTo quantify the risk of gastric cancer in first-degree relatives of patients with the cancer.METHODSA comprehensive literature search was performed. Case-control trials comparing the frequency of a positive family history of gastric cancer in patients with gastric cancer, vs non-gastric cancer controls were retrieved. Studies with missed or non-extractable data, studies in children, abstracts, and duplicate publications were excluded. A meta-analysis of pooled odd ratios was performed using Review Manager 5.0.25. We performed subgroup analysis on Asian studies and a sensitivity analysis based on the quality of the studies, type of the outcome, sample size, and whether studies considered only first-degree relatives.RESULTSThirty-two relevant studies out of 612 potential abstracts (n = 80690 individuals) were included. 19.0% of the patients and 10.9% of the controls had at least one relative with gastric cancer (P < 0.00001). The pooled relative risk for the development of gastric cancer in association with a positive family history was 2.35 (95%CI: 1.96-2.81). The Cochran Q test for heterogeneity was positive (P < 0.00001, I² = 92%). After excluding the three outlier studies with the highest relative risks, heterogeneity remained significant (P < 0.00001, I² = 90%). The result was not different among Asian studies as compared to others and remained robust in several sensitivity analyses. In the 26 studies which exclusively analysed the history of gastric cancer in first-degree relatives, the relative risk was 2.71 (95%CI: 2.08-3.53; P < 0.00001).CONCLUSIONIndividuals with a first-degree relative affected with gastric cancer have a risk of about 2.5-fold for the development of gastric cancer. This could be due to genetic or environmental factors. Screening and preventive strategies should be developed for this high-risk population.

Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene

AIM:To evaluate the biological and clinical characteristics of miR-622 in gastric cancer. METHODS:We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time polymerase chain reaction. Functional analysis of miR-622 expression was assessed in vitro in gastric cancer cell lines with miR-622 precursor and inhibitor. The roles of miR-622 in tumorigenesis and tumor metastasis were analyzed using a stable miR-622 expression plasmid in nude mice. A luciferase reporter assay was used to assess the effect of miR-622 on inhibitor of growth family,member 1 (ING1) expression. RESULTS:Expression of miR-622 was down-regulated in gastric cancer. MiR-622 was found involved in differentia-tion and lymphatic metastasis in human gastric cancer. Ectopic expression of miR-622 promoted invasion,tumorigenesis and metastasis of gastric cancer cells both in vitro and in vivo. ING1 is a direct target of miR-622. CONCLUSION:These findings help clarify the molecular mechanisms involved in gastric cancer metastasis and indicate that miR-622 modulation may be a bona fide treatment of gastric cancer.

Stomach cancer screening and preventive behaviors in relatives of gastric cancer patients

AIM:To investigate gastric cancer screening and preventive behaviors among the relatives of patients with gastric cancer[i.e.,gastric cancer relatives(GCRs)].METHODS:We examined the Korean National Health and Nutrition Examination Survey 2005(KNHANESⅢ) database and compared the gastric cancer screening and preventive behaviors of GCRs(n=261)with those of non-GCRs(n=454)and controls without a family history of cancer(n=2842).RESULTS:The GCRs were more likely to undergo gastric cancer screening compared with the control group(39.2%vs 32.3%,adjusted odds ratio:1.43,CI:1.05-1.95),although the absolute screening rate was low.Dietary patterns and smoking rates did not differ significantly between the groups,and a high proportion of GCRs reported inappropriate dietary habits(i.e.,approximately 95%consumed excessive sodium,30% were deficient in vitamin C,and 85%were deficient in dietary fiber).CONCLUSION:The gastric cancer screening and preventive behaviors of GCRs have yet to be improved.To increase awareness among GCRs,systematic family education programs should be implemented.

Vestigial like family member 3 is a novel prognostic biomarker for gastric cancer

BACKGROUND Vestigial like family member 3(VGLL3)is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma,but its role in gastric cancer(GC)is unclear.AIM To explore the expression pattern and clinical significance of VGLL3 in GC.METHODS Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE,GEPIA,and ONCOLNC databases.The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot,respectively.In addition,the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry(IHC),and the patients were accordingly classified into the high and low expression groups.The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses.RESULTS Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues(P=0.003),and associated with the tumor TNM stage(P=0.0163).The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group,as per both GEPIA(P=0.0057)and ONCOLNC(P=0.01).The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues(P<0.001)in a cohort of 30 GC patients.Furthermore,high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation(P<0.05)in a cohort of 172 patients.Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group(P=0.019).Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis.In addition,the prognostic risk model nomogram showed that VGLL3 was the most important indicator,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.613 for 3-year survival and 0.706 for 5-year survival.Finally,the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway.CONCLUSION VGLL3 is overexpressed in GC tissues and associated with a poor prognosis,indicating its potential as a novel prognosis biomarker and therapeutic target for GC.

Comparison of patients by family history with gastric and non-gastric cancer

AIM:To compare the gastric cancer(GC) patients by their family history with gastric and non-GC.METHODS:Positive family histories within seconddegree relatives and clinicopathological features were obtained for 256 patients.RESULTS:Of the 256 probands,112(76 male,36 female) were incorporated into familial GC(FGC) group:at least two GC members;144(98 male,46 female) were included in the non-FGC group(relatives only affected with non-GCs).Of 399 tumors in relatives(181 from FGC against 212 from non-FGC),GC was the most frequent,followed by esophageal,hepatocellular,and colorectal cancer.Nasopharyngeal cancer was next to lung cancer but prior to breast and urogenital cancers.Most affected members aggregated within first-degree relatives(FGC:66 siblings,48 fathers,31 mothers,four offspring;non-FGC:56 fathers,55 siblings,43 mothers,and 15 offspring).The ratio of males to females in affected first-degree relatives was usually higher in male probands.Paternal history of GC was a slight risk for GC in males(OR = 1.19,95% CI:0.53-2.69),while risk of GC by maternal history of non-GCs was increased in females(OR = 0.46,95% CI:0.22-0.97).Diffuse-GC was the major histological type in all subgroups.Difference in tumor sites between thetwo groups was derived from an excess of upper sites in non-FGC female probands.CONCLUSION:Distribution of associated non-GCs in a family history of GC may vary with geographic areas.GC may have different genetic and/or environmental etiology in different families,and a certain subtype may be inherited in a female-influenced fashion.

Prognostic significance of KIF23 expression in gastric cancer

BACKGROUND Kinesin super family 23(KIF23)is a member of the KIF family,and it plays an important role in mitosis and cytokinesis.Loss of expression can cause mitotic arrest.The Oncomine database is one of the largest oncogene chip databases in the world,and is an integrated data mining platform for cancer gene information.By querying the database,differences in expression between tumor tissue and normal tissue can be determined.AIM To study the expression and prognostic significance of KIF23 in gastric cancer(GC).METHODS We used immunohistochemistry to compare the expression of KIF23 in GC and normal gastric tissues.We mined the data on the expression and prognosis of KIF23 in GC using Oncomine and Kaplan-Meier plotter database.RESULTS Compared with normal gastric tissues,KIF23 expression was increased in GC tissues,and correlated with T,N,and tumor-node-metastasis stages.Survival analysis showed that patients with high expression of KIF23 had a poor overall survival.There were five studies in the Oncomine database in which expression of KIF23 was significantly higher in GC tissues than in normal gastric tissues(P<0.05).Kaplan-Meier plotter database analysis showed that recurrence-free survival,overall survival,distant metastasis free survival,and post progression survival of patients with high expression of KIF23 were lower than those of patients with low expression.Further stratified analysis found that prognostic survival indicators worsened in patients with T2 and T3 poorly differentiated adenocarcinoma with high expression of KIF23.CONCLUSION KIF23 is highly expressed in GC and is associated with a poor prognosis of patients.It may be of great significance in the diagnosis,treatment,and prognostic evaluation of GC.

Global whole family based-Helicobacter pylori eradication strategy to prevent its related diseases and gastric cancer

Helicobacter pylori (H.pylori) infects approximately 50% of the world population.The multiple gastrointestinal and extra-gastrointestinal diseases caused by H.pylori infection pose a major healthcare threat to families and societies;it is also a heavy economic and healthcare burden for countries that having high infection rates.Eradication of H.pylori is recommended for all infected individuals.Traditionally,"test and treat"and"screen and treat"strategies are available for various infected populations.However,clinical practice has noticed that these strategies have some shortfalls and may need refinement,mostly due to the fact that they are not easily manageable,and are affected by patient compliance,selection of treatment population and cost-benefit estimations.Furthermore,it is difficult to control infections from the source,therefore,development of additional,compensative strategies are encouraged to solve the above problems and facilitate bacteria eradication.H.pylori infection is a family-based disease,but few studies have been performed in a whole family-based approach to curb its intra-familial transmission and the development of related diseases.In this work,a third,novel whole family-based H.pylori eradication strategy is introduced.This approach screens,identifies,treats and follows up on all H.pylori-infected individuals in entire families to control H.pylori infection among family members,and reduce its long-term complications.This strategy is high-risk population-oriented,and able to reduce H.pylori spread among family members.It also has good patient-family compliance and,importantly,is practical for both high and low H.pylori-infected communities.Future efforts in these areas will be critical to initiate and establish healthcare policies and management strategies to reduce H.pylori-induced disease burden for society.

Unusual immunohistochemical“null”pattern of four mismatch repair proteins in gastric cancer:A case report

BACKGROUND Immunohistochemical(IHC)staining for mismatch repair(MMR)proteins is useful for gastric cancer treatment and prognosis.Different IHC staining patterns reflect the complex biological phenomena underlying MMR deficiency.We herein report a rare IHC staining pattern of four MMR-related proteins in gastric cancer.CASE SUMMARY A“null”IHC staining pattern of four MMR-related proteins,including MLH1,PMS2,MSH2,and MSH6,in a 67-year-old male patient with gastric cancer pT3N3aM0 revealed promoter hypermethylation of MLH1.Next-generation sequencing showed that these four genes exhibited changes.One of these was the somatic mutation of the missing copy number in exon 14 of MSH2.Mutation analysis using peripheral blood showed no germline mutations in these four genes.The patient had no history of personal or family tumor history.We classified this case as sporadic.The patient returned to normal after operation,and there were no signs of tumor metastasis and recurrence.After six cycles of adjuvant chemotherapy,the patient was discharged in a stable condition.The patient had a mild reaction to chemotherapy and a good prognosis.At present,16 mo after the operation,the patient's condition is stable.CONCLUSION Abnormal MMR protein expression,helpful for individualized follow-up care,helped identify a sporadic case lacking familial clinical management implications.

基于蛋白激酶NEK9/MTA2信号通路泛素化修饰探讨胃癌的转移机制

目的:基于永离有丝分裂基因A相关激酶9(NEK9)/转移相关肿瘤基因家族2(MTA2)信号通路泛素化修饰探讨胃癌(GC)的转移机制。方法:使用癌症基因组图谱(TCGA)和Kaplan-Meier Plotter数据库分析NEK9表达与GC分期、预后之间的关联。体外实验中,将GC细胞分为:对照组、shNC组、shNEK9组、shNC+NC-OE组、shNEK9+NC-OE组和shNEK9+MTA2-OE组。分别采用MTT和Transwell法测定细胞的增殖、迁移和侵袭,并通过Western blot检测NEK9、MTA2、上皮间充质转化(EMT)标记和PI3K/AKT信号通路蛋白表达。结果:TCGA数据库分析显示,NEK9 mRNA在肿瘤组织中的表达明显上调,并且与TNM分期较晚和NEK9高表达者的预后较差密切相关。此外,NEK9在7个GC细胞系中的表达明显高于正常胃上皮GES-1细胞(P<0.05)。与对照组相比,shNEK9组细胞活力、相对集落形成、EdU阳性细胞数、侵袭和迁移细胞数均显著降低(P<0.05)。此外,在shNEK9组细胞中,E-钙粘蛋白水平上调(P<0.05),波形蛋白水平下调(P<0.05)。通过免疫共沉淀试验证明NEK9与MTA2有相互作用。NEK9敲低加速了HGC-27细胞中MTA2的降解,并且MTA2泛素化在NEK9沉默的细胞中增加。与shNEK9+NC-OE组组相比,shNEK9+MTA2-OE组相对集落形成、EdU阳性细胞数和迁移和侵袭数均显著增加(P<0.05)。结论:NEK9在GC中明显上调,其敲低在体外抑制GC细胞的生长和转移。NEK9可能通过去泛素化途径稳定MTA2进而激活PI3K-AKT信号通路来对GC细胞产生促癌影响。

胃癌中COL6基因家族的生物信息学分析

目的通过生物信息学方法系统性地分析COL6基因家族各成员在胃癌中的作用。方法利用TIMER2.0和GEPIA2数据库分析COL6家族基因在胃癌组织中的表达与不同病理分期的关系。通过Kaplan-Meier Plotter数据库分析COL6基因家族各成员表达水平与胃癌患者总生存期(OS)和无复发生存期(RFS)之间的关系。通过cBioPortal数据库分析胃癌患者中COL6基因的遗传变异、共表达与邻近基因网络情况。通过STRING数据库和仙桃学术绘制COL6家族蛋白互作网络图,并进行功能富集分析,分析其作用机制。结果在胃腺癌中,COL6基因家族(COL6A1、COL1A2、COL6A3、COL6A4P1、COL6A4P2、COL6A5和COL6A6)的表达相对于邻近的正常组织上调,且COL6A1(P=0.000367)、COL6A2(P=0.00017)、COL6A3(P<0.001)、COL6A4P1(P=0.864)、COL6A4P2(P=0.355)、COL6A5(P=0.187)和COL6A6(P=0.302)的表达与胃癌患者的病理分期相关。高表达的COL6A1(P=0.047)、COL6A2(P=0.017)、COL6A3(P=0.02)、COL6A5(P=0.028)和COL6A6(P=0.025)胃癌患者生存率均较低,而COL6A4P1(P=0.006)、COL6A4P2(P=0.0091)和COL6A6(P=0.002)与患者的转移或复发相关。KEGG功能富集分析显示差异表达的COL6A1、COL6A2、COL6A3、COL6A4P1、COL6A4P2、COL6A5、COL6A6的细胞功能与病灶黏附、细胞外基质受体相互作用信号通路有关。结论COL6家族是胃癌预后的潜在生物标志物,且与胃癌的免疫浸润相关。

幽门螺杆菌定植和铁死亡基因表达与胃癌临床病理及预后的关系

目的探讨幽门螺杆菌定植与铁死亡基因表达与胃癌临床病理及预后的关系。方法选取159例于2018年1月至2019年9月在空军军医大学第一附属医院肿瘤防治中心接受D2胃癌根治术的胃癌患者。收集患者年龄、性别、术前常规实验室测量、术后肿瘤特征和生存期等资料。采用免疫组织化学分析癌旁正常组织和胃癌组织中溶质载体家族1成员5(SLC1A5)表达,采用酶联免疫吸附试验评估术前血清幽门螺杆菌免疫球蛋白G(IgG)抗体水平。结果有无幽门螺杆菌感染患者在T分期、淋巴结转移数量≥3和SLC1A5表达水平方面差异有统计学意义(P<0.05)。与癌旁正常组织相比,胃癌组织中SLC1A5免疫组织化学评分显著增加(6.35±3.40 vs 3.08±1.75,t=10.75,P<0.001)。SLC1A5低表达和高表达患者在肿瘤等级、神经侵犯、T分期、幽门螺杆菌感染方面差异有统计学意义(P<0.05)。Cox分析显示,幽门螺杆菌感染(HR=3.786、95%CI=2.284~6.274)、肿瘤等级(HR=1.877、95%CI=1.254~2.810)、SLC1A5表达(HR=1.112、95%CI=1.035~1.193)是胃癌患者预后不良的独立影响因素(P<0.05)。将幽门螺杆菌感染、肿瘤等级、SLC1A5表达三者组合,构建HSG评分,HSG 0分、HSG 1分、HSG 2分、HSG 3分死亡事件的发生率依次为6.25%(1/16)、34.29%(12/35)、64.91%(37/57)、88.23%(45/51),不同评分之间的总体生存概率比较差异有统计学意义(Log-rank=31.06,P<0.001)。结论幽门螺杆菌感染、肿瘤等级、SLC1A5表达是胃癌患者不良预后的独立影响因素,基于三者组合构建的HSG评分能有效地对胃癌根治性切除后患者的结局进行分层,并有助于改善临床决策和确定适当的治疗。

阿帕替尼联合替吉奥治疗晚期胃癌患者的效果及对IL-6家族因子的影响

目的:探究阿帕替尼联合替吉奥治疗晚期胃癌患者的效果及对白介素-6(IL-6)家族因子的影响。方法:将2020年4月—2022年11月辽阳市中心医院的90例晚期胃癌患者依据随机数字表法分为对照组45例和观察组45例。对照组采用替吉奥进行治疗,观察组则采用阿帕替尼联合替吉奥进行治疗。比较两组的总有效率、各类不良反应发生率、治疗前后的生存质量[癌症患者生命质量评定30问卷(QLQ-C30)评分]及IL-6家族因子[IL-6、白介素-27(IL-27)及白介素-31(IL-31)]。结果:观察组的总有效率显著高于对照组,差异有统计学意义(P<0.05)。两组的各类不良反应发生率比较,差异均无统计学意义(P>0.05)。治疗前两组的QLQ-C30各维度评分及IL-6家族因子比较,差异均无统计学意义(P>0.05),治疗2个周期及4个周期后观察组的QLQ-C30各维度评分均显著高于对照组,IL-6家族因子均显著低于对照组,差异均有统计学意义(P<0.05)。结论:阿帕替尼联合替吉奥在晚期胃癌患者中的应用效果较好,安全性值得肯定,且可显著改善患者的生存质量及IL-6家族因子的表达,因此在晚期胃癌患者中的应用价值较高。

X射线对胃癌细胞和人脐静脉内皮细胞LOX家族成员的不同影响

目的比较不同剂量X射线对人低分化粘液样胃腺癌细胞MGC-803和人脐静脉内皮细胞(HUVEC)赖氨酰氧化酶(LOX)家族成员的影响,为了解X射线辐射后不同细胞中基因和蛋白的改变提供依据。方法0、2、4、6、8和10 Gy剂量X射线辐射MGC-803和HUVEC细胞,用细胞增殖实验检测细胞致死率并计算细胞半数致死量(LD 50),确定后序测试剂量组;Realtime PCR、Western blot、ELISA及Amplex Red过氧化氢法分别检测辐射后细胞LOX家族成员mRNA丰度、蛋白相对量、分泌量及LOX酶活性变化;Western blot方法分析X射线辐射对细胞p-p38MAPK和p-Erk1/2MAPK影响。结果X射线辐射后的LD 50胃癌MGC-803为8.2 Gy,HUVEC为6 Gy,后序试验选用0、2、4和6 Gy剂量组。MGC-803细胞经各剂量X射线辐射后LOXL1、LOXL2和LOXL4的mRNA均下调,而LOX的mRNA上调(P<0.05);2 Gy组LOX和LOXL4的蛋白和酶分泌水平低于0 Gy组(P<0.05);4 Gy组LOX、LOXL1、LOXL2和LOXL4的蛋白和分泌低于0 Gy组(P<0.05);6 Gy组LOXL1的蛋白和分泌低于0 Gy组(P<0.05);但LOXL3的mRNA、蛋白和分泌在2 Gy组均高于0 Gy组(P<0.05)。HUVEC中,2 Gy组LOXL1和LOXL3的mRNA、蛋白和酶分泌水平均显著高于0 Gy组(P<0.05);4 Gy组LOX、LOXL1、LOXL3和LOXL4的mRNA、蛋白和酶分泌水平均较0 Gy组升高(P<0.05);6 Gy组LOXL2和LOXL4的mRNA、蛋白和酶分泌水平均较0 Gy组升高(P<0.05)。2 Gy和6 Gy组HUVEC的LOX酶活性增强(P<0.05)。MGC-803细胞的2 Gy和6 Gy组p-p38、p-p42、p-p44较0 Gy组上调(P<0.05);HUVEC经各剂量辐射p-p38、p-p42和p-p44均上调(P<0.05)。结论X射线辐射对两种细胞作用不同,一定剂量X射线辐射上调HUVEC的LOX及其家族成员的产生、分泌和酶活性,下调胃癌细胞MGC-803的除LOXL3外其他成员的产生和分泌。

Despite shared susceptibility loci, esophageal squamous cell carcinoma embraces more familial cancer than gastric cardia adenocarcinoma in the Taihang Mountains high-risk region of northern central China

Background In China, esophageal squamous cell carcinoma （ESCC） and gastric cardia adenocarcinoma （GCA） share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal. Methods The percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University. Results A positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males （P 〈0.000） and 25.0%, 22.3%, 23.9%, and 9.8% in females （P 〈0.0001）. Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females （ both P 〈0.0001） for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2：1 for upper, middle, lower third ESCC and GCA （P〈0.0001）. For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age 〉50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist. Conclusions The proportion of familial cancer in upper gastrointestinal carcinomas decreases by the priamry site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis

Fundic gland polyps are now commonly recognized during endoscopy. These polyps are benign, often multiple and usually detected in the gastric body and fundus. In the past, these polyps were sometimes associated with familial adenomatous polyposis. In recent years, it has become evident that increasing numbers of these polyps are being detected during endoscopic studies, particularly in patients treated with proton pump inhibitors for prolonged periods. In some, dysplastic changes in these polyps have also been reported. Recent studies have suggested that there may be no increase in risk of colon cancer with long-term proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance, particularly in those genetically predisposed to colon cancer, is still warranted.