Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Current gene therapy for stomach carcinoma

Gastric cancer is common in China [1-42],and its early diagnosis and treatment in advanced stage are difficult [31-50].In recent years ,gene study in cancer is a hotspot ,and great progress has been achieved [41-80] .Cancer gene therapy has shifted from the imagination into the laboratory and clinical trials.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

自身免疫性胃炎与胃肿瘤的研究进展

自身免疫性胃炎(AIG)是一种由自身免疫功能异常所致的胃炎,临床常表现为恶性贫血或神经系统症状,内镜下通常可见胃体黏膜萎缩,可伴有血清抗壁细胞抗体和(或)抗内因子抗体阳性。有研究表明,AIG是胃神经内分泌瘤和胃癌的危险因素,因此内镜下诊断并随访监测AIG至关重要。本文就AIG与胃肿瘤的研究进展作一综述。

舒适度负面影响因子溯源护理干预对晚期胃癌化疗患者效果

目的分析舒适度负面影响因子溯源护理干预对晚期胃癌化疗患者的效果。方法选取2022年1月-2023年12月我院治疗的晚期胃癌化疗患者88例,按随机数字表法分为对照组和观察组,各44例。对照组实施常规护理干预,观察组在对照组的基础上实施舒适度负面影响因子溯源护理干预。比较两组心理状态、舒适度、自我效能感、化疗毒副反应等。结果两组干预后心理弹性量表(CD-RISC)、Kolcaba舒适状况量表(GCQ)、自我效能量表(CDSES)评分均高于干预前,且观察组高于对照组,观察组化疗毒副反应发生率低于对照组(P<0.05)。结论舒适度负面影响因子溯源护理干预能有效调整晚期胃癌化疗患者心理状态,提高舒适度,增强自我效能感,减少化疗毒副反应,可应用于临床。

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

胃癌(GC)是极具异质性和侵袭性的消化系统恶性肿瘤之一,传统化疗药物及曲妥珠单抗等人表皮生长因子受体2(HER2)靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此,研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷,但在某些情况下无效或产生耐药,这与HER2在某些GC细胞中低表达有关,HER2低表达(HER2 IHC1+或IHC2+/ISH-)约占全部类型的40%~60%,但在临床实践中,这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物(ADC)的出现为HER2阳性GC提供了新的治疗选择,凭借其精准高效的抗肿瘤作用,有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性,相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述,并讨论HER2靶向ADC在应用和研发过程中面临的挑战。

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients

AIM To investigate the interference ofmethionine.free parenteral nutrition plus 5-Fu（-MetTPN+5-Fu）in gastric cancer cell kineticsand the side effects of the regimen.METHODS Fifteen patients with advancedgastric cancer were randomly divided into twogroups,7 patients were given preoperatively aseven-day course of standard parenteralnutrition in combination with a five-day courseof chemotherapy（sTPN+5-Fu）,while the other8 patients were given methionine-deprivedparenteral nutrition and 5-Fu（-MetTPN+5-Fu）.Cell cycles of gastric cancer and normal mucosawere studied by flow cytometry（FCM）.Bloodsamples were taken to measure the serumprotein,methionine（Met）and cysteine（Cys）levels,and liver and kidney functions.RESULTS As compared with the resultsobtained before the treatment,the percentage ofG0/G1 tumor cells increased and that of S phasedecreased in the-MetTPN+5-Fu group,while thecontrary was observed in the sTPN+5-Fu group.Except that the ALT,AST and AKP levels wereslightly increased in a few cases receiving-MetTPN+5-Fu,all the other biochemicalparameters were within normal limits.Serum Cys level decreased slightly after the treatmentin both groups.Serum Met level of patientsreceiving sTPN+5-Fu was somewhat higher aftertreatment than that before treatment;however,no significant change occurred in the -MetTPN+5-Fu group,nor operative complications in bothgroups.CONCLUSION -MetTPN+5-Fu exerted asuppressive effect on cancer cell proliferation,probably through a double mechanism ofcreating a state of'Met starvation'adverse tothe tumor cell cycle,and by allowing 5-Fu to killspecifically cells in S phase.Preoperative short-term administration of -MetTPN+5-Fu had littleundesirable effect on host metabolism.

Neoadjuvant chemotherapy vs upfront surgery for gastric signet ring cell carcinoma:A retrospective,propensity score-matched study

BACKGROUND The benefit of neoadjuvant chemotherapy for patients with signet-ring cell carcinoma of the stomach is controversial.AIM To evaluate the perioperative and long-term outcomes of neoadjuvant chemotherapy for locally advanced gastric signet-ring cell carcinoma.METHODS This retrospective study identified patients with locally advanced signet-ring cell carcinomas of the stomach(cT3/4 and cN any)diagnosed from January 2012 to December 2017 by using the clinical Tumor-Node-Metastasis(cTNM)staging system.We performed 1:1 propensity score matching(PSM)to reduce bias in patient selection.The histologic and prognostic effects of neoadjuvant chemotherapy were assessed.The overall survival rates were used as the outcome measure to compare the efficacy of neoadjuvant chemotherapy vs surgery-first treatment in the selected patients.RESULTS Of the 144 patients eligible for this study,36 received neoadjuvant chemotherapy,and 108 received initial surgery after diagnosis.After adjustment by PSM,36 pairs of patients were generated,and baseline characteristics,including age,sex,American Society of Anesthesiologists score,tumor location,and cTNM stage,were similar between the two groups.The R0 resection rates were 88.9%and 86.1%in the surgery-first and neoadjuvant chemotherapy groups after PSM,respectively(P=1.000).The median follow-up period was 46.4 mo.The 5-year overall survival rates of the neoadjuvant chemotherapy group and surgery-first group were 50.0%and 65.0%(P=0.235),respectively,before PSM and 50%and 64.7%(P=0.192),respectively,after PSM.Multivariate analyses conducted before and after PSM showed that NAC was not a prognostic factor.CONCLUSION Neoadjuvant chemotherapy provides no survival benefit in patients with locally advanced gastric signet-ring cell carcinoma.For resectable gastric signet-ring cell carcinoma,upfront surgery should be the primary therapy.

Auricular-Plaster Therapy Plus Acupuncture at Zusanli for Postoperative Recovery of Intestinal Function

In order to relieve the abdominal distension and other discomforts due to gastrointestinal dysfunction after abdominal operations, the patients were treated by auricular-plaster therapy plus acupuncture at Zusanli (ST 36). 12 (92.4%) of the 13 cases in the treatment group showed recovery of normal peristalsis within 72 hours after operations, while that in 13 cases of the control group was 46.1%, indicating that auricular-plaster therapy plus acupuncture at Zusanli (ST 36) may promote postoperative recovery of the intestinal function.

Pathological response measured using virtual microscopic slides for gastric cancer patients who underwent neoadjuvant chemotherapy

BACKGROUND Although pathological response is a common endpoint used to assess the efficacy of neoadjuvant chemotherapy (NAC) for gastric cancer, the problem of a low rate of concordance from evaluations among pathologists remains unresolved. Moreover, there is no globally accepted consensus regarding the optimal evaluation. A previous study based on a clinical trial suggested that pathological response measured using digitally captured virtual microscopic slides predicted patients’ survival well. However, the pathological concordance rate of this approach and its usefulness in clinical practice were unknown. AIM To investigate the prognostic utility of pathological response measured using digital microscopic slides in clinical practice. METHODS We retrospectively evaluated pathological specimens of gastric cancer patients who underwent NAC followed by surgery and achieved R0 resection between March 2009 and May 2015. Residual tumor area and primary tumor beds were measured in one captured image slide, which contained the largest diameter of the resected specimens. We classified patients with < 10% residual tumor relative to the primary tumorous area as responders, and the rest as non-responders;we then compared overall survival (OS) and relapse-free survival (RFS) between these two groups. Next, we compared the prognostic utility of this method using conventional Japanese criteria. RESULTS Fifty-four patients were evaluated. The concordance rate between two evaluators was 96.2%. Median RFS of 25 responders and 29 non-responders was not reached (NR) vs 18.2 mo [hazard ratio (HR)= 0.35, P = 0.023], and median OS was NR vs 40.7 mo (HR = 0.3, P = 0.016), respectively. This prognostic value was statistically significant even after adjustment for age, eastern cooperative oncology group performance status, macroscopic type, reason for NAC, and T- and Nclassification (HR = 0.23, P = 0.018). This result was also observed even in subgroup analyses for different macroscopic types (Borrmann type 4/non-type 4) and histological types (differentiated/undifferentiated). Moreover, the adjusted HR for OS between responders and non-responders was lower in this method than that in the conventional histological evaluation of Japanese Classification of Gastric Carcinoma criteria (0.23 vs 0.39, respectively). CONCLUSION The measurement of pathological response using digitally captured virtual microscopic slides may be useful in clinical practice.

POTENTIATION OF DOCETAXEL ANTITUMOR ACTIVITY BY BATIMASTAT AGAINST MOUSE FORESTOMACH CARCINOMA

Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB 94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. Methods and results. In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB 94 on MFC cell showed that docetaxel but not BB 94 had a significant cytotoxicity, and the effect of docetaxel wasn’t enhanced by BB 94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20mg/kg; doxorubicin: 6mg/kg) every 4 days for 3 injections (q4d×3), even that of BB 94 (30mg/kg i.p. qd×20) was observed. Tumor growth inhibition was greater for docetaxel batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB 94 (33.0%), and the effect of docetaxel could be potentiated by BB 94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log10 tumor cell kill. Conclusion. Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB 94 enchances the antitumor activity of docetaxel.

Retrovirus-mediated antisense RNA to bcl-2 alter the biological behavior of stomach carcinoma MGC-803 cell lines

AIM To demonstrate whether bcl 2 gene can affect or alter biological behavior of a stomach carcinoma cell line MGC 803. METHODS To transduct a retrovirus containing bcl 2 antisense RNA to MGC 803 cells and then to analyse the Bcl 2 protein expression in the cells by Western blotting. To observe the morphology alteration, detect the G1 phase arrest by FCM, inhibition of proliferation by MTT method and tumorigenicity in nude mice. RESULTS The MGC anti bcl 2 cells shows contact inhibition, morphological alteration, from round or near round to shuttle like, decelerated growth rate, G1 phase arrest and weakened tumorigenicity in nude mice unlike the control (MGC neo cells). CONCLUSION Antisense RNA to bcl 2, not only can induce apoptosis, but also reverse the biological behavior of MGC 803 cells. This would be a potential application to the gene therapy for stomach cancers.

肠内营养对晚期胃癌化疗患者营养指标的影响

目的 研究肠内营养对晚期胃癌化疗患者营养指标的影响。方法 选取2020年1月至2022年1月40例晚期胃癌化疗患者作为研究对象,采用随机数字表法分为对照组(20例)与研究组(20例)。给予对照组患者常规化疗方案治疗,研究组患者在对照组的基础上联合肠内营养治疗,2组患者均连续治疗42 d。比较2组患者治疗前后身体测量指标、生活质量及营养指标情况。结果 与治疗前相比,治疗后研究组患者右上臂周围、左上臂周围、体重指数(BMI)、血红蛋白(Hb)、白蛋白(ALB)、转铁蛋白(TF)、前清蛋白(PA)水平升高,对照组患者右上臂周围、左上臂周围、BMI、血Hb、ALB、TF、PA水平降低,研究组高于对照组;与治疗前相比,治疗后2组患者躯体功能、角色功能、情绪功能、认知功能和社会功能评分降低,其中研究组高于对照组(P值均<0.05)。结论 肠内营养可有效缓解晚期胃癌化疗患者可有效缓解营养不良症状,改善生活质量,优化营养状态指标和提高预后。

穴位注射新斯的明用于胃癌腹腔镜根治术后快速康复管理中的价值

【目的】探讨穴位注射用于胃癌腹腔镜根治术后快速康复管理中的价值。【方法】将80例行胃癌腹腔镜根治术患者随机分为两组,每组40例,观察组在围术期行快速康复外科(FTS)管理的基础上加用足三里穴位注射新斯的明,对照组仅围术期实施FTS管理。比较两组手术相关指标,不同时点血清C反应蛋白(CRP)、白蛋白(ALB)水平及T淋巴细胞水平,比较两组不良反应发生情况和12个月生存情况。【结果】观察组下床活动时间、肛门排气时间、首次经口流质饮食时间、住院时间均显著少于对照组(P<0.05)。两组术后1 d、3 d的血清CRP水平显著高于术前,血清ALB水平显著低于术前(P<0.05);两组术后3 d血清CRP水平显著低于术后1 d,ALB水平显著高于术后1 d(P<0.05);观察组术后不同时点血清CRP水平显著低于对照组,血清ALB水平显著高于对照组(P<0.05)。两组术后3 d的CD3^(+)、CD4^(+)、CD8^(+)均显著低于本组术前(P<0.05);两组术后3 d的CD4^(+)/CD8^(+)与本组术前比较,差异均无统计学意义(P>0.05);观察组术后3 d的CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)均显著高于对照组(P<0.05)。观察组不良反应总发生率显著低于对照组(P<0.05)。两组患者术后12个月生存率比较,差异无统计学意义(P>0.05)。【结论】在采用FTS管理的基础上加用足三里穴位注射新斯的明有助于腹腔镜胃癌根治术后患者更快康复,减轻机体对刺激的应激反应,改善患者的营养状态,调控机体免疫功能,降低不良反应发生率。

改良RECIST评估方法对局部进展期胃癌新辅助化疗后疗效评估的探索

目的探索临床上简便实用的局部进展期胃癌新辅助化疗后疗效评估方法。方法分析2016年1月至2020年12月期间福建省肿瘤医院收治的最大淋巴结短径≥1.5 cm并行新辅助化疗及手术治疗的局部进展期胃癌病例的临床资料,应用高分辨率CT测量最大淋巴结短径和胃部病灶最大厚度,分别以最大淋巴结短径和两者之和为评估值,建立两种影像学评估方法,mRECIST①和mRECIST②,分析两种改良影像学评估方法与RECIST1.1无瘤生存率(DFS)的相关性。结果79例患者纳入研究,共筛选出短径≥1.5 cm的转移性淋巴结103枚,淋巴结短径为2.0(1.5~4.6)cm。术前CT评估肿瘤最大厚度为1.3(0.5~3.5)cm,淋巴结短径为1.2(0.4~3.5)cm。依据RECIST1.1标准进行疗效评价,PR 52例(65.8%)、SD 25例(31.6%)、PD 2例(2.5%)。反应组(CR和PR组)和未反应组(SD和PD组)的3年DFS差异有统计学意义(53.4 vs.21.6%,P=0.001),反应组与未反应组的死亡风险比,差异有统计学意义(HR=0.386;95%CI:0.211~0.706,P=0.002)。依据mRECIST①标准进行疗效评价,PR 53例(67.1%)、SD 24例(30.4%)、PD 2例(2.5%);反应组和未反应组的3年无瘤生存率差异有统计学意义(52.3%vs.22.4%,P=0.003),反应组对未反应组的死亡风险比,差异有统计学意义(HR=0.413;95%CI:0.226~0.756,P=0.004)。依据mRECIST②标准进行疗效评价,PR 48例(60.8%)、SD 29例(36.7%)、PD 2例(2.5%);反应组和未反应组的3年DFS差异有统计学意义(59.0%vs.18.4%,P=0.001),反应组对未反应组的死亡风险比,差异有统计学意义(HR=0.376;95%CI:0.204~0.691,P=0.002)。结论采用最大淋巴结短径与胃部病灶最大厚度之和对局部进展期胃癌新辅助化疗后进行疗效评价优于只用最大淋巴结短径或淋巴结短径之和进行疗效评价,是一种可选用的简便有效的疗效评估方法。

胃Castleman病1例并文献复习

Castleman病(Castleman disease)又称“巨大淋巴结病”或“血管滤泡性淋巴结增生症”[1]。该病于1956年首次由Castleman等[2]描述为局部纵隔淋巴结肿大,其特征为淋巴滤泡数量增多,生发中心退化,毛细血管显著增生,包括滤泡和滤泡间内皮增生,故命名为Castleman病。胃Castleman病十分罕见,目前国内外仅有个别病例报道。因其病因和发病机制尚未完全阐明,临床上极易发生漏诊和误诊。本文报告苏州大学附属第一医院1例确诊胃Castleman病病例的诊治经过并进行相关文献复习,以期进一步加强对该病的认识。

胃癌靶点Claudin 18.2的研究进展

我国胃癌的早期诊断率低,大多数病人就诊时已为晚期,失去了根治性手术的机会。晚期胃癌目前以化疗药物治疗为主,但化疗药物具有选择性低、毒副作用大等缺点。随着分子生物学的进展,靶向药物对胃癌的治疗展现出了良好的前景,成为晚期胃癌治疗新的选择。目前,对胃癌有成效的靶向治疗以抗人表皮生长因子受体-2(HER-2)药物为主,抗血管内皮生长因子药物及免疫检查点抑制剂对胃癌的治疗也取得了一定的成效。近年来,Claudin18.2靶点成为最具前景的胃癌治疗性靶点。该研究针对Claudin18.2的研究进展展开综述。

腹腔镜联合胃镜在36例胃间质瘤手术中的应用

目的总结腹腔镜联合胃镜术中定位治疗胃间质瘤（GSTs）的经验。方法 36例诊断为GSTs（直径小于或等于5cm）的患者应用腹腔镜联合胃镜术中定位技术,分别行胃腔外锲形切除术、经胃腔肿瘤外翻切除术、胃部分切除术等。结果 36例均在双镜联合下顺利找到肿瘤并成功行局部切除,术后胃动力障碍1例,下肢深静脉血栓2例。手术时间50~140 min,术中岀血20~220 mL,术后4~5 d进流质饮食,平均住院时间8.3 d。结论应用腹腔镜联合胃镜定位治疗GSTs具有定位准确、手术时间短、创伤小、恢复快等优点,具有较好的临床实用价值。

氧化砷抑制胃癌SGC-7901细胞增殖和诱导凋亡作用

目的研究氧化砷对胃癌细胞的增殖抑制和诱导凋亡作用．方法应用细胞集落形成实验、ＭＴＴ，ＴＵＮＥＬ染色、流式细胞仪技术，研究氧化砷对胃癌细胞ＳＧＣ７９０１的增殖抑制、细胞毒和诱导凋亡的作用．结果氧化砷能显著抑制胃癌细胞ＳＧＣ７９０１的生长，５μｍｏｌ／Ｌ氧化砷抑制程度明显强于１μｍｏｌ／Ｌ（Ｐ＜００５），５μｍｏｌ／Ｌ和１μｍｏｌ／Ｌ的氧化砷作用后的细胞集落形成率分别为１２４％±３３％和６８％±２６％，明显低于对照组的２０６％±５７％（Ｐ＜００１）．氧化砷对胃癌细胞具有较强的细胞毒作用，１０μｍｏｌ／Ｌ氧化砷作用２４ｈ细胞杀伤率为２４６％，４８ｈ接近５０％．氧化砷作用于细胞后，可看到较为典型的细胞凋亡的形态学变化：细胞核固缩，染色质凝集，呈新月型紧贴于核膜周边，核碎裂，染色质片断化，凋亡小体形成等．流式细胞仪ＤＮＡ直方图上出现典型的亚二倍体“凋亡峰”．ＴＤＴ染色法显示，细胞凋亡指数为７３％～１５１％．氧化砷的细胞毒作用呈时间和剂量依赖性，且表现为细胞周期特异性，作用４８ｈ后，ＳＧＣ７９０１细胞的细胞周期变化明显，Ｇ０／Ｇ１期细胞从５４２％下降到１７７％，而Ｇ２／Ｍ期细胞则从２０?