Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Prostaglandin F_(2α)synthase promotes oxaliplatin resistance in colorectal cancer through prostaglandin F_(2α)-dependent and F_(2α)-independent mechanism

BACKGROUND Oxaliplatin(Oxa)is the first-line chemotherapy drug for colorectal cancer(CRC),and Oxa resistance is crucial for treatment failure.Prostaglandin F_(2α)synthase(PGF 2α)(PGFS),an enzyme that catalyzes the production of PGF_(2α),is involved in the proliferation and growth of a variety of tumors.However,the role of PGFS in Oxa resistance in CRC remains unclear.AIM To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC.METHODS The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels.Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance(HCT116-OxR and HCT8-OxR)and their parental cell lines(HCT116 and HCT8)to assess its influence on cell proliferation,chemoresistance,apoptosis,and DNA damage.For determination of the underlying mechanisms,CRC cells were examined for platinum-DNA adducts and reactive oxygen species(ROS)levels in the presence of a PGFS inhibitor or its products.RESULTS Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues.Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dosedependent manner.Furthermore,overexpression of PGFS in parental CRC cells significantly attenuated Oxainduced proliferative suppression,apoptosis,and DNA damage.In contrast,knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells(HCT116-OxR and HCT8-OxR)accentuated the effect of Oxa treatment in vitro and in vivo.The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa.Treatment with the PGFS-catalyzed product PGF_(2α)reversed the effect of PGFS knockdown on Oxa sensitivity.Interestingly,PGFS inhibited the formation of platinum-DNA adducts in a PGF_(2α)-independent manner.PGF_(2α)exerts its protective effect against DNA damage by reducing ROS levels.CONCLUSION PGFS promotes resistance to Oxa in CRC via both PGF_(2α)-dependent and PGF_(2α)-independent mechanisms.

SLFN11基因表达对SW480细胞L-OHP敏感度的影响

目的探讨SLFN11基因表达对奥沙利铂抑制结直肠癌细胞株SW480生长的影响。方法通过SLFN11基因沉默(siRNA)降低SLFN11基因表达水平,并通过RT-qPCR和Western blot法方法鉴定SLFN11基因mRNA和蛋白表达水平;利用MTT实验验证奥沙利铂对SW480细胞株生长增殖的影响;通过流式细胞仪检测SW480细胞周期及细胞凋亡情况。结果siRNA干扰可特异性地显著降低SW480细胞株SLFN11基因的表达和蛋白表达水平,MTT实验发现SLFN11基因沉默组较基因未干扰组,奥沙利铂对SW480细胞株的生长抑制明显减低(P<0.05),而且减弱奥沙利铂对SW480细胞株的细胞凋亡的诱导(P<0.01),减少G 2/M期细胞周期阻滞(P<0.01)。结论SLFN11基因低表达可以降低SW480细胞对奥沙利铂的敏感度,可能预测奥沙利铂治疗结直肠癌细胞的疗效。

HOXB8 contributed to oxaliplatin chemo-resistance in colon cancercells by activating STAT3

Background:Homeobox B8(HOXB8),a member of HOX family,plays a key role in the development of colorectal cancer(CRC).However,the function of HOXB8 in oxaliplatin(OXA)resistance in CRC is still unclear.This study investigated the role and precise molecular mechanism of HOXB8 in OXA-resistant CRC cells.Methods:The cell viability was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay,and the colony forming ability was determined by colony formation assay.The silencing RNA(siRNA)approach was used to knockdown HOXB8 in CRC cells while the lentiviral transfection system was used to establish stable HOXB8 overexpressing CRC cells.The protein and mRNA levels were evaluated by western blot and real-time reverse transcription-polymerase chain reaction.Results:HOXB8 expression was upregulated in OXA-resistant HCT116 cells(HCT116/OXA)compared to its level in the parent HCT116 cells.Knockdown of HOXB8 significantly inhibited CRC cell growth by suppressing the signal transducer and activator of transcription 3(STAT3)pathway.HOXB8 knockdown also potentiated cytotoxicity of OXA in CRC cells.Inversely,HOXB8 overexpression attenuated OXAinduced growth inhibition of HCT116 cells and RKO cells by activating STAT3 signaling.HOXB8 knockdown effectively inhibited HCT116/OXA cell viability regardless of OXA treatment by suppressing STAT3 signaling.Conclusions:These results shed light on the important functions of HOXB8 in OXA-resistant CRC and suggested that targeting HOXB8 might be an effective therapeutic strategy for select OXA-resistant CRC patients.

Treatment outcome analysis of bevacizumab combined with cyclophosphamide and oxaliplatin in advanced pseudomyxoma peritonei

BACKGROUND Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome.Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment.However,there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP.Regimens for colorectal cancer are often used clinically,but there is no uniform standard for late-stage treatment.AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin(Bev+CTX+OXA)is effective for treatment of advanced PMP.The primary study endpoint was progression-free survival(PFS).METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen(bevacizumab 7.5 mg/kg ivgtt d1,oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1,q3w)in our center from December 2015 to December 2020.Objective response rate(ORR),disease control rate(DCR)and incidence of adverse events were evaluated.PFS was followed up.Kaplan-Meier method was used to draw survival curve,and log-rank test was used for comparison between groups.Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.RESULTS A total of 32 patients were enrolled.After 2 cycles,the ORR and DCR were 3.1%and 93.7%,respectively.The median follow-up time was 7.5 mo.During the follow-up period,14 patients(43.8%)had disease progression,and the median PFS was 8.9 mo.Stratified analysis showed that the PFS of patients with a preoperative increase in CA125(8.9 vs 2.1,P=0.022)and a completeness of cytoreduction score of 2-3(8.9 vs 5.0,P=0.043)was significantly longer than that of the control group.Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS(HR=0.245,95%CI:0.066-0.904,P=0.035).CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second-or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated.A preoperative increase in CA125 is an independent prognostic factor of PFS.

Cerium Oxide Nanoparticles Protect against Oxaliplatin Induced Testicular Damage: Biochemical, Histological, Immunohistochemical, and Genotoxic Study

Oxaliplatin is a chemotherapeutic drug used for colorectal cancer treatment. The testicular toxic effect is one of its recorded toxicities which resulted in a few studies. Oxidative stress could be a direct cause of this testicular toxicity. Cerium oxide nanoparticles (CONPs) are optimistic antioxidants for applications in medicine. The aim of the work is to study the protective effect of CONPs on testicular toxicity induced by oxaliplatin in rats. Forty adult male albino rats were divided into 4 groups: Control group, CONPs group (60 mg/kg, 5 times/week), Oxaliplatin group (4 mg/kg, twice/week), and Oxaliplatin & CONPs group, for 4 weeks. Seventy-two hours after the last administration, blood samples were taken for hormonal levels and testes were used for both histopathology and immunohistochemical microscopic examination. Sperm smears were also performed and their results were statistically analyzed to detect any sperm abnormalities. Oxaliplatin increased MDA levels. SOD and GPx activity was decreased. GSH levels were decreased. Also, it decreased the sperm cell count and serum testosterone, and anti-Müllerian hormon. In the testicular sections, significant histopathology changes were seen and immunohistochemical examination confirmed these results. Upon supplementation of CONPs with oxaliplatin decreased MDA levels. SOD and GPx activity was increased, and GSH did not change. In testicular sections, normal morphology was seen. Also, there was an increase in the sperm cell count and serum testosterone anti-Müllerian with significant improvement of testicular architecture, and immunohistochemical examination confirmed these results. The utilization of CONPs produced significant protection against all of the above-mentioned changes.

Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin

BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.

不同营养状态对结直肠癌患者奥沙利铂化疗致周围神经毒性(OIPN)的影响

目的 探讨营养状态对结直肠癌患者发生奥沙利铂致周围神经毒性(OIPN)的影响。方法 选取2022年7月至2023年5月无锡市江南大学附属医院收治的219例结直肠癌患者,收集患者资料,运用SPSS 26.0对影响因素进行统计分析。结果 219例结直肠癌患者中有144例发生了OIPN,作为OIPN组;75例没有发生OIPN,作为非OIPN组。Spearman分析显示两组患者并发症、营养风险筛查2002(NRS2002)评分、白蛋白、血红蛋白等指标差异有统计学意义(P <0.05);Logistic回归分析显示白蛋白与并发症是OIPN发生的独立危险因素,在此基础上构建Nomogram预测模型,为临床评估和预测OIPN发生提供新的方法和思路。结论 白蛋白水平低下与发生并发症是OIPN的独立危险因素,其中白蛋白水平与患者的营养状况密切相关,该预测模型对预测结直肠癌患者OIPN发生具有较好的临床应用价值。

CaMKK2调控肝细胞癌化疗耐药性的作用和机制

目的 探讨钙/钙调蛋白依赖性蛋白激酶激酶2(calcium/calmodulin-dependent protein kinase kinase 2,CaMKK2)调控肝细胞癌(hepatocellular carcinoma, HCC)化疗耐药性的作用及其机制。方法 (1)为了检测CaMKK2在HCC耐药细胞株中的表达变化,将实验分为亲本组和耐药组。采用浓度梯度递增法建立奥沙利铂(oxaliplatin, OXA)耐药细胞株MHCC97H/OXA和Hep3B/OXA。采用Western blot检测CaMKK2的磷酸化和总蛋白表达水平。(2)为了检测CaMKK2对肝细胞癌化疗药性的调控作用,将实验分为对照组和CaMKK2敲除组。采用CRISPR/Cas9技术敲除MHCC97H/OXA和Hep3B/OXA细胞株中的CaMKK2基因表达,采用Western blot验证CaMKK2敲除效率。采用细胞计数试剂盒-8(cell counting kit-8,CCK-8)实验检测CaMKK2敲除对MHCC97H/OXA和Hep3B/OXA细胞株细胞存活率的影响。采用流式细胞术检测CaMKK2敲除对MHCC97H/OXA和Hep3B/OXA细胞株凋亡的影响。采用Western blot检测CaMKK2敲除对微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3,LC3)、p62、腺苷酸活化蛋白激酶(adenosine 5′-monophosphate-activated protein kinase, AMPK)和UNC-51样激酶1(UNC51-like kinase 1,ULK1)蛋白表达水平的影响。(3)为了验证CaMKK2对肝细胞癌化疗药性的调控作用,将实验分为CaMKK2敲除+空载体组和CaMKK2敲除+CaMKK2载体组。采用Western blot检测CaMKK2的蛋白表达水平。采用CCK-8实验检测重新表达CaMKK2对CaMKK2敲除的细胞耐药性的影响。采用Western blot检测重新表达CaMKK2对CaMKK2敲除的细胞中AMPK、ULK1和LC3蛋白表达水平的影响。结果 (1)与亲本组相比,耐药组HCC细胞株中CaMKK2的总蛋白表达水平无显著变化(P>0.05),而CaMKK2的磷酸化水平显著升高(P<0.01)。(2)与对照组比较,CaMKK2敲除组细胞中CaMKK2表达水平显著减少(P<0.01)。与对照组比较,CaMKK2敲除组HCC耐药细胞对OXA的敏感性显著提高(P<0.05),OXA细胞凋亡率显著升高(P<0.01)。与对照组比较,CaMKK2敲除组LC3Ⅱ/LC3Ⅰ显著降低,p62蛋白水平显著升高,p-AMPK/AMPK以及p-ULK1/ULK1显著降低(均P<0.01)。(3)与CaMKK2敲除+空载体组比较,CaMKK2敲除+CaMKK2载体组HCC耐药细胞对OXA的敏感性显著降低(P<0.01),LC3Ⅱ/LC3Ⅰ、p-AMPK/AMPK和p-ULK1/ULK1显著升高(P<0.01)。结论 基因敲除CaMKK2有效逆转HCC化疗耐药性,其作用机制与调控AMPK/ULK1介导的自噬通路相关。

以替吉奥为基础联合阿帕替尼三药方案对进展期胃癌患者的影响

目的研究以替吉奥为基础联合阿帕替尼对进展期胃癌患者免疫功能及血清细胞因子水平的影响。方法选取本院89例进展期胃癌患者,采用随机数字表法分组,对常规组44例采用奥沙利铂、替吉奥治疗,对研究组45例增加阿帕替尼,对比两组患者血清肿瘤标志物水平、血清细胞因子水平、免疫功能和不良反应。结果研究组治疗后癌胚抗原(CEA)、糖类抗原125(CA125)水平低于常规组(P<0.05);研究组治疗后血清γ-干扰素(IFN-γ)、正常上皮细胞特异性-1基因(NES1)、白介素-10(IL-10)和肿瘤坏死因子-α(TNF-α)水平高于常规组(P<0.05);研究组治疗后T淋巴细胞(CD8+)水平低于常规组,CD3+、CD4+水平高于常规组(P<0.05)。结论以替吉奥为基础联合阿帕替尼三药方案对进展期胃癌患者效果确切,能够有效提高患者的免疫功能,改善血清细胞因子水平,降低血清肿瘤标志物水平,安全性高。

含奥沙利铂化疗方案联合艾迪注射液对晚期结直肠癌患者免疫功能及生活质量的影响

目的探讨含奥沙利铂化疗方案联合艾迪注射液对晚期结直肠癌(CRC)患者免疫功能及生活质量的影响。方法选取2021年3月至2023年3月江西中医药大学附属医院收治的93例CRC患者,按照随机数字表法分为对照组(47例)与试验组(46例)。对照组给予含奥沙利铂化疗方案治疗,在其基础上,试验组给予艾迪注射液治疗,比较两组临床疗效、免疫功能、肿瘤标志物水平与生活质量。结果试验组总有效率、CD4^(+)与CD3^(+)、生活质量总改善率均高于对照组,CD8^(+)、糖类抗原125(CA125)、癌胚抗原(CEA)与糖类抗原19-9(CA19-9)均低于对照组,差异有统计学意义(P<0.05)。结论含奥沙利铂化疗方案、艾迪注射液联合治疗晚期CRC疗效确切,可降低肿瘤标志物水平,增强免疫功能,提高生活质量。

多西他赛腹腔灌注联合SOX方案化疗与DOS方案化疗对晚期胃癌伴癌性腹水患者生活质量的影响比较

目的比较多西他赛腹腔灌注联合SOX方案化疗与DOS方案化疗对晚期胃癌伴癌性腹水患者生活质量的影响。方法选取2016年1月—2018年1月广西医科大学第一附属医院收治的晚期胃癌伴癌性腹水的患者78例,按1∶1的比例随机分为D-SOX组(双通路模式)和DOS组(传统模式),每组39例。D-SOX组腹腔灌注多西他赛联合SOX方案化疗,DOS组采取多西他赛、奥沙利铂、替吉奥传统模式方案化疗。2组均以21 d为1个周期,每2个周期评估疗效,化疗2~8周期。通过EORTC生活质量测定量表QLQ-C30与QLQ-STO22对2组最佳生活质量改善、改善程度的差异及恶化风险等进行评估。结果D-SOX组中功能量表包括躯体功能、社会功能以及症状量表中与腹水导致相关的症状均有明确改善。特别是在呼吸困难、吞咽困难领域、进食受限领域、口干及疼痛方面,D-SOX组在延缓恶化时间方面较DOS组有明显优势(HR:0.48~0.54)。结论多西他赛腹腔灌注联合SOX方案化疗较DOS方案化疗有更好的生活质量改善优势,对患者体力改善、症状缓解及延缓恶化均有积极作用。

肝窦阻塞综合征的研究进展

肝窦阻塞综合征(HSOS)也被称为肝小静脉闭塞病,是一类由各种原因导致的肝血窦阻塞和肝小静脉闭塞纤维化的肝脏血管性疾病。本文系统阐述了HSOS的认识过程和命名演变、病因和发病机制、临床表现、诊断与鉴别诊断、预防和治疗等方面的研究进展。HSOS可发生于接受骨髓造血干细胞移植清髓处理、放射/化学治疗和摄入含吡咯生物碱药物的人群,常见临床表现为腹胀、肝区胀痛、腹水、黄疸、肝大等。针对不同病因,HSOS的诊断标准也不相同,需要与其他药物性肝病、肝静脉流出道梗阻等疾病相鉴别。去纤苷和低分子肝素分别对造血干细胞和吡咯生物碱相关的HSOS具有治疗作用,奥沙利铂化疗导致的HSOS目前尚无有效治疗药物。

阿帕替尼联合mFOLFOX6化疗对ⅢB期、Ⅳ期胃癌患者疗效及血清肿瘤标志物水平的影响

目的:探讨阿帕替尼联合mFOLFOX6化疗(亚叶酸钙、氟尿嘧啶联合奥沙利铂)对ⅢB期、Ⅳ期胃癌患者疗效及血清肿瘤标志物水平的影响。方法:选取2017年12月—2019年10月靖江市人民医院收治的102例ⅢB期、Ⅳ期胃癌患者作为研究对象,采用随机数表法将患者分为联合组(阿帕替尼联合mFOLFOX6化疗)与参照组(mFOLFOX6化疗治疗),各51例。比较两组治疗效果、血管内皮生长因子(VEGF)、胰岛样素生长因子1(IGF-1)、生存时间、不良反应。结果:联合组总有效率高于参照组,差异有统计学意义(P<0.05);治疗后,两组血清IGF-1、VEGF水平较治疗前降低,且联合组低于参照组,差异有统计学意义(P<0.05);联合组总平均生存时间长于参照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:阿帕替尼联合mFOLFOX6化疗对ⅢB期、Ⅳ期胃癌患者疗效显著,可明显降低血清IGF-1、VEGF水平,延长总平均生存时间,且安全可靠。

替吉奥联合奥沙利铂对老年胃癌患者胃动力相关激素及基质金属蛋白酶-2、基质金属蛋白酶-9的影响

目的探讨替吉奥联合奥沙利铂对老年胃癌患者胃动力相关激素及基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的影响。方法选取128例老年胃癌患者为研究对象,随机分成对照组(n=64)与观察组(n=64)。对照组给予替吉奥治疗,观察组给予替吉奥联合奥沙利铂治疗。观察2组的胃动力相关激素[胃动素(MTL)、血管活性肠肽(VIP)]、MMP-2与MMP-9、肿瘤标志物[癌胚抗原(CEA)、糖类抗原125(CA125)、糖类抗原19-9(CA19-9)]、临床疗效以及不良反应发生情况。分析胃动力相关激素与MMP-2、MMP-9及肿瘤标记物水平的相关性。结果治疗后,2组MTL低于治疗前,VIP高于治疗前,且观察组MTL低于对照组,VIP高于对照组,差异有统计学意义(P<0.05)。治疗后,2组MMP-2、MMP-9及CEA、CA125、CA19-9低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。观察组总有效率为70.31%,高于对照组的53.13%,差异有统计学意义(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。MTL与MMP-2、MMP-9、CEA、CA125、CA19-9呈负相关(P<0.05);VIP与MMP-2、MMP-9、CEA、CA125、CA19-9呈正相关(P<0.05)。结论替吉奥联合奥沙利铂治疗老年胃癌患者的效果较好,且安全性较高。MTL、VIP与MMP-2、MMP-9及CEA、CA125、CA19-9在老年胃癌患者的疾病发展中起相互关联作用。

胃癌根治术后奥沙利铂联合卡培他滨辅助化疗患者预后的影响因素分析及列线图模型构建

目的分析胃癌根治术后奥沙利铂联合卡培他滨辅助化疗患者预后的影响因素,并构建预后列线图模型。方法232例胃癌患者均行胃癌根治切除术及D2淋巴结清扫术,术后采用奥沙利铂联合卡培他滨化疗。对所有患者随访3年,根据随访期间的生存情况,将患者分为生存组和死亡组,比较两组患者的临床特征。采用Cox风险比例回归模型分析胃癌患者预后的影响因素并构建列线图预测模型,采用校正曲线、决策曲线验证列线图模型的预测效能及可靠性。结果死亡组(n=85)肿瘤大小≥5 cm、胃切除方式为全胃切除术、TNM分期为Ⅲ期、中性粒细胞与淋巴细胞比值(NLR)≥4、癌胚抗原(CEA)≥6 ng/ml、预后营养指数(PNI)﹤45患者比例均明显高于生存组(n=147),差异均有统计学意义(P﹤0.01)。Cox回归分析结果显示,肿瘤大小≥5 cm、胃切除方式为全胃切除术、TNM分期为Ⅲ期、NLR≥4、CEA≥6 ng/ml、PNI﹤45均是胃癌患者预后不良的危险因素(P﹤0.05)。该列线图模型预测胃癌患者预后的C指数为0.933(95%CI:0.901~0.964),该列线图模型的校准曲线在对患者预后风险的观测值和预测值之间表现出高度一致性。该列线图模型的阈值﹥0.04,其临床净收益显著高于肿瘤大小、胃切除方式、TNM分期、NLR、CEA、PNI单一预测因子。结论肿瘤大小≥5 cm、胃切除方式为全胃切除术、TNM分期为Ⅲ期、NLR≥4、CEA≥6 ng/ml、PNI﹤45均是胃癌根治术后奥沙利铂联合卡培他滨辅助化疗患者预后不良的危险因素,基于此构建的列线图预测模型预测价值较高,可为临床改善患者预后提供依据。

表柔比星联合奥沙利铂经导管动脉栓塞化疗治疗中晚期原发性肝癌患者的临床疗效

目的目的探讨表柔比星联合奥沙利铂经导管动脉栓塞化疗(TACE)治疗中晚期原发性肝癌患者的临床疗效。方法方法根据治疗方法的不同将96例中晚期原发性肝癌患者分为对照组(n=43)和观察组(n=53),对照组患者采取奥沙利铂TACE治疗,观察组患者采取表柔比星联合奥沙利铂TACE治疗。比较两组患者的临床疗效、肿瘤标志物[血管内皮生长因子(VEGF)、甲胎蛋白(AFP)]水平、肝功能指标[丙氨酸转氨酶(ALT)、白蛋白(ALB)、总胆红素(TBIL)]及不良反应发生情况。结果结果观察组患者的总有效率高于对照组,差异有统计学意义(P﹤0.05)。治疗后,两组患者VEGF、AFP水平均低于本组治疗前,观察组患者VEGF、AFP水平均低于对照组,差异均有统计学意义(P﹤0.05)。治疗后,两组患者ALT、TBIL水平均低于本组治疗前,ALB水平均高于本组治疗前,观察组患者ALT、TBIL水平均低于对照组,ALB水平高于对照组,差异均有统计学意义(P﹤0.05)。两组患者的不良反应总发生率比较,差异无统计学意义(P﹥0.05)。结论结论表柔比星联合奥沙利铂TACE治疗中晚期原发性肝癌患者,可提高临床疗效,降低肿瘤标志物水平,改善肝功能,且不会增加不良反应。