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 ...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.展开更多
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 investi...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.展开更多
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 p...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.展开更多
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 func...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.展开更多
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...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.展开更多
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 t...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.展开更多
1文献类型治疗2证据水平1b3文献来源De Gramont A, Figer A, Seymour M, et al.Leucovorin and fluorouacil with or without oxaliplatin as first-line treatment in advanced colorectal cancer [J]. J Clin Oncol, 2000,18(16)
AIM To investigate whether micro RNA(mi R)-34 a mediates oxaliplatin(OXA) resistance of colorectal cancer(CRC) cells by inhibiting macroautophagy via the transforming growth factor(TGF)-β/Smad4 pathway.METHODS miR-34...AIM To investigate whether micro RNA(mi R)-34 a mediates oxaliplatin(OXA) resistance of colorectal cancer(CRC) cells by inhibiting macroautophagy via the transforming growth factor(TGF)-β/Smad4 pathway.METHODS miR-34 a expression levels were detected in CRC tissues and CRC cell lines by quantitative real-time polymerase chain reaction. Computational search, functional luciferase assay and western blotting were used to demonstrate the downstream target of miR-34 a in CRC cells. Cell viability was measured with Cell Counting Kit-8. Apoptosis and macroautophagy of CRC cells were analyzed by flow cytometry and transmission electron microscopy, and expression of beclin I and LC3-II was detected by western blotting.RESULTS Expression of miR-34 a was significantly reduced while expression of TGF-β and Smad4 was increased in CRC patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased mi R-34 a levels and increased TGF-β and Smad4 levels in both parental cells and the OXA-resistant CRC cells. Activation of macroautophagy contributed to OXA resistance in CRC cells. Expression levels of Smad4 and miR-34 a in CRC patients had a significant inverse correlation and overexpressing mi R-34 a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34 a and increased drug resistance by activating macroautophagy in CRC cells.CONCLUSION miR-34 a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-β/Smad4 pathway.展开更多
This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin,with a partial response and normalization of α f...This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin,with a partial response and normalization of α fetoprotein,which allowed curative surgery.The potential synergy between these three drugs needs to be confirmed,and is currently being investigated in a randomized phase Ⅱ trial.展开更多
Background:Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer.This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1,oxaliplatin,and leucovori...Background:Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer.This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1,oxaliplatin,and leucovorin(SOL) in the treatment of Chinese patients with metastatic colorectal cancer(mCRC).Methods:Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin(85 mg/m2) on day 1,oral S-1 twice daily(80-120 mg per day) on day 1-7,and leucovorin twice daily(50 mg per day)simultaneously with S-1,every 2 weeks.Results and discussion:Forty patients were enrolled in our study.In total,296 cycles of SOL were administered.The overall response rate was 50.0%.At a median follow-up of 27 months,progression-free survival and overall surviva were 7.0 months(95%confidence interval[CI]6.0-10.6 months) and 22.2 months(95%CI 15.1-29.3 months),respectively.The most common grade 3/4 non-hematological adverse events were diarrhea(n = 8,20.0%),nausea(n = 3,7.5%),and vomiting(n = 3,7.5%).The most common grade 3/4 hematological toxicities were thrombocytopenia(n = 3,7.5%),neutropenia(n = 1,2.5%),and abnormal alanine transaminase/aspartate transaminase levels(n = 1,2.5%).There was one treatment-related death.Conclusions:The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC.Trial registration:Clinical trial展开更多
AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic ...AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.展开更多
AIM To investigate the safety and efficacy of S-1 plus oxaliplatin(SOX) as an adjuvant chemotherapy regimen in gastric cancer(GC) after D2 dissection.METHODS GC Patients who underwent D2 gastrectomy from September 200...AIM To investigate the safety and efficacy of S-1 plus oxaliplatin(SOX) as an adjuvant chemotherapy regimen in gastric cancer(GC) after D2 dissection.METHODS GC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage ⅠB-ⅢC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin(XELOX) regimen. Disease-free survival(DFS) and overall survival(OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed.Of 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that(44.6%) in the surgery alone group(P = 0.001); and the estimated five-year OS was 68.3% which was higher than that(45.8%) of surgery alone group(P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups(P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS(P = 0.340) and OS(P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia(22.6%), leukopenia(8.9%) and thrombocytopenia(5.6%).CONCLUSION Compared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage ⅠB-ⅢC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.展开更多
AIM To determine the efficacy and safety of transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed in hepatocellular carcinoma(HCC) with major portal...AIM To determine the efficacy and safety of transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed in hepatocellular carcinoma(HCC) with major portal vein tumor thrombus(MPVTT).METHODS eighty-six patients with MPVTT accepted routine embolization. The catheter was kept in the hepatic artery and oxaliplatin(50 mg in 250 m L of glucose) was infused by pump for 4 h,followed by raltitrexed(2 mg in 100 m L of 0.9% saline) infusion by pump for the next 1 h. The efficacy and safety were evaluated afterthe transarterial chemoembolization(TACe).RESULTS Full or partial embolization was achieved in 86 cases,where all the cases received low dose continuous hepatic arterial infusion chemotherapy. Complete responses(CRs),partial responses(PRs),stable disease(SD),and disease progression(PD) for intrahepatic disease were observed in 0,45,20,and 21 patients,respectively. The 1-,2-and 3-year overall survival rates of the 86 patients were 40.7%,22.1%,and 8.1% respectively,and the median survival time was 8.7 mo. Complication was limited. CONCLUSION TACE with low dose continuous hepatic arterial infusion of oxaliplatin and raltitrexed could be an option in MPVTT patient; it was shown to be effective in patients with advanced HCC with MPVTT with less toxicity.展开更多
AIM:To investigate whether silencing Fas-associated phosphatase 1(FAP-1)expression enhances the efficiency of chemotherapy for colon carcinoma with oxaliplatin.METHODS:Expression of FAP-1 in mRNA and protein was detec...AIM:To investigate whether silencing Fas-associated phosphatase 1(FAP-1)expression enhances the efficiency of chemotherapy for colon carcinoma with oxaliplatin.METHODS:Expression of FAP-1 in mRNA and protein was detected by reverse transcription polymerase chain reaction(RT-PCR)and flow cytometry.Small interfering RNA(siRNA)was designed according to the FAP-1 mRNA sequence.Cell proliferation was evaluated by methyl thiazolyl tetrazolium(MTT)assay.Anenxin V-and propidine iodine(PI)were assayed by flow cytometry for the detection of apoptosis. RESULTS:The expression of FAP-1 was increased in SW480 cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480 cells silenced the expression of FAP-1 and consequently abolished the inhibitory function of Fas/FasL-mediated apoptosis pathway,thus increasing the efficacy of chemotherapy for colon carcinoma with oxaliplatin. CONCLUSION:RNA interference combined with conventional chemotherapy is more effective against colon cancer.展开更多
Oxaliplatin,an anticancer drug commonly used to treat colorectal cancer and other tumors,has a number of serious side effects,most notably neuropathy and ototoxicity.To gain insights into its ototoxic profile,oxalipla...Oxaliplatin,an anticancer drug commonly used to treat colorectal cancer and other tumors,has a number of serious side effects,most notably neuropathy and ototoxicity.To gain insights into its ototoxic profile,oxaliplatin was applied to rat cochlear organ cultures.Consistent with it neurotoxic propensity,oxaliplatin selectively damaged nerve fibers at a very low dose 1μM.In contrast,the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher(50μM).Oxailiplatin-induced cochlear lesions initially increased with dose,but unexpectedly decreased at very high doses.This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms.Previous studies have demonstrated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide(NAD+).To determine if NAD+would protect spiral ganglion axons and the hair cells from oxaliplatin damage,cochlear cultures were treated with oxaliplatin alone at doses of 10μM or 50μM respectively as controls or combined with 20 mM NAD+.Treatment with 10μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers,but spared cochlear hair cells.However,when cochlear cultures were treated with 10μM oxaliplatin plus 20 mM NAD+,most auditory nerve fibers were intact.50μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apoptotic characteristics of cell fragmentations.However,50μM oxaliplatin plus 20 mM NAD+treatment greatly reduced neuronal degenerations and hair cell missing.The results suggested that NAD+provides significant protection against oxaliplatin-induced neurotoxicity and ototoxicity,which may be due to its actions of antioxidant,antiapoptosis,and energy supply.展开更多
Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates.To improve long-term outcomes,perioperative chemotherapies are combined with surgery.Human epidermal growth factor rece...Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates.To improve long-term outcomes,perioperative chemotherapies are combined with surgery.Human epidermal growth factor receptor 2(HER2)overexpression had been noted in gastric cancer;therefore,trastuzumab has been used occasionally in this setting.A 63-year-old male Chinese patient,who was diagnosed with adenocarcinoma in the gastric antrum,as well as lymph node metastases along the left gastric and hepatic artery,and left adrenal area,was admitted to our hospital.HER2 expression was positive,and cluster amplification was detected in a fluorescence in situ hybridization assay.The patient received three cycles of a neoadjuvant trastuzumab/oxaliplatin/capecitabine regimen.He subsequently underwent distal gastrectomy,D2+lymphadenectomy,left adrenalectomy,cholecystectomy and BillrothⅡanastomosis.Treatment was continued with another five postoperative cycles of the same medication and trastuzumab application for 1 year.No recurrence has been observed 18 mo after the operation.Trastuzumab as perioperative and adjuvant medication,in combination with oxaliplatin and capecitabine for a HER2-overexpressing advanced gastric adenocarcinoma,led to recurrence-free survival of at least 18 mo after surgery.展开更多
Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug concentrations.Here we report the case of a 61-year-old man who presente...Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug concentrations.Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy.The patient was treated with a combination of gemcitabine and oxaliplatin using HAI.The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI.The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper.HAI of gemcitabine-oxaliplatin should be evaluated in further clinical trials.展开更多
AIM:To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). METHODS: Seventy patients with ad...AIM:To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). METHODS: Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m2 po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m2 iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeat-ed for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed. RESULTS: The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ2 = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ2 = 0.032 and P = 0.857). Effi cacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ2 = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05). CONCLUSION: The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.展开更多
Objective:To investigate the safety,efficacy,and prognostic factors of hepatic arterial infusion chemotherapy(HAIC)with raltitrexed and oxaliplatin post-transarterial chemoembolization(TACE)for unresectable hepatocell...Objective:To investigate the safety,efficacy,and prognostic factors of hepatic arterial infusion chemotherapy(HAIC)with raltitrexed and oxaliplatin post-transarterial chemoembolization(TACE)for unresectable hepatocellular carcinoma(uHCC).Methods:Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited.The primary endpoint was overall survival(OS),and secondary endpoint was progression-free survival(PFS).The overall response rate(ORR)was evaluated using the modified Response Evaluation Criteria in Solid Tumors.Toxicity was assessed according to the Common Terminology Criteria for Adverse Events(v4.0).The OS and prognostic factors were analyzed using the Kaplan-Meier method,log-rank test,and Cox regression models.Results:Three(8.1%)patients achieved complete response,17(46.0%)patients achieved partial response,and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months,respectively.The common toxicities included grade 3-4 increased aspartate aminotransferase levels(8/37,21.6%),grade 1-2 hyperbilirubinemia(75.7%,28/37),nonspecific abdominal pain and fever,and grade 2-3 thrombocytopenia(18.9%,7/37);no patients developed grade 3-4 neutropenia.Univariate analysis showed that the tumor diameter(≤50 mm,p=0.028),Barcelona Clinic Liver Cancer(BCLC)stage(p=0.012),hepatitis B virus DNA level(p=0.033),and derived neutrophil-to-lymphocyte ratio(dNLR;derived neutrophils/leukocytes minus neutrophils)(p=0.003)were predictive factors for prognosis.Multivariate analysis showed that patients with BCLC stage B disease(p=0.029)and dNLR<2 before therapy(p=0.004)had better prognosis.Conclusions:HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC;in particular,those with BCLC stage B and dNLR<2 have better prognosis.展开更多
Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a re...Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.展开更多
基金The Natural Science Foundation of Shandong Province,No.ZR2020MH238.
文摘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.
基金supported by the Natural Science Foundation of Zhejiang Province(LZ22H160006)Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(LHDMY22H160002)Wenzhou Municipal Science and Technology Bureau(Y20180085).
文摘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.
基金the S and T Program of Hebei,No.22377704DMedical Science Research Project of Hebei Province,No.20190510Postgraduate’s Innovation Fund Project of Hebei Province,No.CXZZBS2021077.
文摘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.
基金Supported by This work was supported by the Natural Science Foundation of Gansu Province,China,No.17JR5RA272 and No.22JR5RA923the Research Fund Project of The First Hospital of Lanzhou University,No.ldyyyn2021-120,No.ldyyyn2020-98 and No.ldyyyn2021-30.
文摘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.
基金Supported by Beijing Municipal Administration of Hospitals’Ascent Plan,No.DFL20180701and Beijing Municipal Grant for Medical Talents Group on Peritoneal Surface Oncology,No.2017400003235J007。
文摘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.
文摘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.
文摘1文献类型治疗2证据水平1b3文献来源De Gramont A, Figer A, Seymour M, et al.Leucovorin and fluorouacil with or without oxaliplatin as first-line treatment in advanced colorectal cancer [J]. J Clin Oncol, 2000,18(16)
基金Supported by Science Foundation of Education Department of Heilongjiang Province,China,no.12541430
文摘AIM To investigate whether micro RNA(mi R)-34 a mediates oxaliplatin(OXA) resistance of colorectal cancer(CRC) cells by inhibiting macroautophagy via the transforming growth factor(TGF)-β/Smad4 pathway.METHODS miR-34 a expression levels were detected in CRC tissues and CRC cell lines by quantitative real-time polymerase chain reaction. Computational search, functional luciferase assay and western blotting were used to demonstrate the downstream target of miR-34 a in CRC cells. Cell viability was measured with Cell Counting Kit-8. Apoptosis and macroautophagy of CRC cells were analyzed by flow cytometry and transmission electron microscopy, and expression of beclin I and LC3-II was detected by western blotting.RESULTS Expression of miR-34 a was significantly reduced while expression of TGF-β and Smad4 was increased in CRC patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased mi R-34 a levels and increased TGF-β and Smad4 levels in both parental cells and the OXA-resistant CRC cells. Activation of macroautophagy contributed to OXA resistance in CRC cells. Expression levels of Smad4 and miR-34 a in CRC patients had a significant inverse correlation and overexpressing mi R-34 a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34 a and increased drug resistance by activating macroautophagy in CRC cells.CONCLUSION miR-34 a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-β/Smad4 pathway.
文摘This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin,with a partial response and normalization of α fetoprotein,which allowed curative surgery.The potential synergy between these three drugs needs to be confirmed,and is currently being investigated in a randomized phase Ⅱ trial.
文摘Background:Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer.This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1,oxaliplatin,and leucovorin(SOL) in the treatment of Chinese patients with metastatic colorectal cancer(mCRC).Methods:Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin(85 mg/m2) on day 1,oral S-1 twice daily(80-120 mg per day) on day 1-7,and leucovorin twice daily(50 mg per day)simultaneously with S-1,every 2 weeks.Results and discussion:Forty patients were enrolled in our study.In total,296 cycles of SOL were administered.The overall response rate was 50.0%.At a median follow-up of 27 months,progression-free survival and overall surviva were 7.0 months(95%confidence interval[CI]6.0-10.6 months) and 22.2 months(95%CI 15.1-29.3 months),respectively.The most common grade 3/4 non-hematological adverse events were diarrhea(n = 8,20.0%),nausea(n = 3,7.5%),and vomiting(n = 3,7.5%).The most common grade 3/4 hematological toxicities were thrombocytopenia(n = 3,7.5%),neutropenia(n = 1,2.5%),and abnormal alanine transaminase/aspartate transaminase levels(n = 1,2.5%).There was one treatment-related death.Conclusions:The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC.Trial registration:Clinical trial
基金Supported by Shanghai Municipal Health Bureau Outstanding Young Clinical Personal Training Project, No. ZYSNXD-YLYSZK025
文摘AIM: To investigate the efficacy and safety of capecitabine and oxaliplatin (CapeOx) for extrahepatic metastasis after local treatment of hepatocellular carcinoma (HCC). METHODS: Thirty-two patients with extrahepatic metastasis of HCC after local treatment were prospectively enrolled. The CapeOx regimen consisted of capecitabine 1000 mg/m 2 taken orally twice daily on days 1-14, and oxaliplatin was administered at a total dose of 100 mg/m 2 on day 1. The treatment was repeated every 3 wk until disease progression or unaccetablle toxicity. Efficacy and safety were assessable for all enrolled patients. The primary objective of this study was to assess the overall response rate. The secondary objectives were to evaluate the overall survival (OS), the time to tumor progression (TTP) and the toxicity profile of the combined strategy. TTP and OS were assessed by the Kaplan-Meier method and differences between the curves were analyzed using the log-rank test. The statistical software SPSS version 15.0 for Windows (SPSS Inc., Chicago, IL, United States) was used for statistical analysis. All P values were 2-tailed, with statistical significance defined byP ≤ 0.05. RESULTS: Thirty-two patients were assessable for efficacy and toxicity. The median follow-up duration was 15 mo (range, 12-20 mo). At the cut-off date of March 31, 2012, 27 patients died due to tumor progression and one patient died of myocardial infarction. Four patients were still alive (three patients with disease progression). OR was 21.9% (n = 7), the stabilization rate was 40.6% (n = 13), and the disease control rate was 62.5%. The responses lasted from 4 to 19 mo (median, 6 mo). Median TTP was 4.2 mo (95%CI: 2.5-7.4), and the median OS time was 9.2 mo (95%CI: 6.5-17.8). The 1-year survival rate was 43.6% (95%CI: 29.0-66.0). In a multivariate analysis, OS was significantly longer in patients with a Child-Pugh class A compared with class B patients (P = 0.014), with a median OS of 10.1 mo vs 5.4 mo, and there were trends towards longer OS (P = 0.065) in patients without portal vein tumor thrombosis. There were no significant effects of age, gender, performance status, cirrhosis, metastatic sites, and level of alpha fetoprotein (AFP) or hepatitis B virus-DNA on OS. Among the 22 patients with elevated AFP levels at baseline (≥ 400 ng/mL), the level fell by more than 50% during treatment in 6 patients (27.3%). The most frequent treatment-related grade 3 to 4 toxicities included leucopenia/neutropenia, transient elevation of aminotransferases, handfoot syndrome and fatigue. CONCLUSION: CapeOx showed modest anti-tumor activity in metastatic HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further study for these patients.
基金Supported by the Thousand Talents of Program of High-end Innovation of Qinghai Province in China(For Jiuda Zhao)the Clinical Oncology Medical Center of Qinghai Province in China,No.2018-SF-113
文摘AIM To investigate the safety and efficacy of S-1 plus oxaliplatin(SOX) as an adjuvant chemotherapy regimen in gastric cancer(GC) after D2 dissection.METHODS GC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage ⅠB-ⅢC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin(XELOX) regimen. Disease-free survival(DFS) and overall survival(OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed.Of 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that(44.6%) in the surgery alone group(P = 0.001); and the estimated five-year OS was 68.3% which was higher than that(45.8%) of surgery alone group(P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups(P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS(P = 0.340) and OS(P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia(22.6%), leukopenia(8.9%) and thrombocytopenia(5.6%).CONCLUSION Compared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage ⅠB-ⅢC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.
基金the National Key R and D Program of China,No.2016YFC0106604the National Natural Science Foundation of China,No.81502591
文摘AIM To determine the efficacy and safety of transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed in hepatocellular carcinoma(HCC) with major portal vein tumor thrombus(MPVTT).METHODS eighty-six patients with MPVTT accepted routine embolization. The catheter was kept in the hepatic artery and oxaliplatin(50 mg in 250 m L of glucose) was infused by pump for 4 h,followed by raltitrexed(2 mg in 100 m L of 0.9% saline) infusion by pump for the next 1 h. The efficacy and safety were evaluated afterthe transarterial chemoembolization(TACe).RESULTS Full or partial embolization was achieved in 86 cases,where all the cases received low dose continuous hepatic arterial infusion chemotherapy. Complete responses(CRs),partial responses(PRs),stable disease(SD),and disease progression(PD) for intrahepatic disease were observed in 0,45,20,and 21 patients,respectively. The 1-,2-and 3-year overall survival rates of the 86 patients were 40.7%,22.1%,and 8.1% respectively,and the median survival time was 8.7 mo. Complication was limited. CONCLUSION TACE with low dose continuous hepatic arterial infusion of oxaliplatin and raltitrexed could be an option in MPVTT patient; it was shown to be effective in patients with advanced HCC with MPVTT with less toxicity.
基金Supported by Research grants from the Science and Technology Foundation of Guangdong Province,No.2006B36002010,2008B030301092,2009B030801005the Foundation of Health Department of Guangdong Province,No.A2005226+2 种基金the foundation of Guangzhou Science and Technology Bureau,No. 2009Y-C011-1the Natural Science Foundation of Guangdong Province,No.7001592the National Natural Science Foundation of China,No.30973505
文摘AIM:To investigate whether silencing Fas-associated phosphatase 1(FAP-1)expression enhances the efficiency of chemotherapy for colon carcinoma with oxaliplatin.METHODS:Expression of FAP-1 in mRNA and protein was detected by reverse transcription polymerase chain reaction(RT-PCR)and flow cytometry.Small interfering RNA(siRNA)was designed according to the FAP-1 mRNA sequence.Cell proliferation was evaluated by methyl thiazolyl tetrazolium(MTT)assay.Anenxin V-and propidine iodine(PI)were assayed by flow cytometry for the detection of apoptosis. RESULTS:The expression of FAP-1 was increased in SW480 cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480 cells silenced the expression of FAP-1 and consequently abolished the inhibitory function of Fas/FasL-mediated apoptosis pathway,thus increasing the efficacy of chemotherapy for colon carcinoma with oxaliplatin. CONCLUSION:RNA interference combined with conventional chemotherapy is more effective against colon cancer.
文摘Oxaliplatin,an anticancer drug commonly used to treat colorectal cancer and other tumors,has a number of serious side effects,most notably neuropathy and ototoxicity.To gain insights into its ototoxic profile,oxaliplatin was applied to rat cochlear organ cultures.Consistent with it neurotoxic propensity,oxaliplatin selectively damaged nerve fibers at a very low dose 1μM.In contrast,the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher(50μM).Oxailiplatin-induced cochlear lesions initially increased with dose,but unexpectedly decreased at very high doses.This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms.Previous studies have demonstrated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide(NAD+).To determine if NAD+would protect spiral ganglion axons and the hair cells from oxaliplatin damage,cochlear cultures were treated with oxaliplatin alone at doses of 10μM or 50μM respectively as controls or combined with 20 mM NAD+.Treatment with 10μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers,but spared cochlear hair cells.However,when cochlear cultures were treated with 10μM oxaliplatin plus 20 mM NAD+,most auditory nerve fibers were intact.50μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apoptotic characteristics of cell fragmentations.However,50μM oxaliplatin plus 20 mM NAD+treatment greatly reduced neuronal degenerations and hair cell missing.The results suggested that NAD+provides significant protection against oxaliplatin-induced neurotoxicity and ototoxicity,which may be due to its actions of antioxidant,antiapoptosis,and energy supply.
文摘Late-stage gastric adenocarcinoma patients have a poor prognosis because of high recurrence rates.To improve long-term outcomes,perioperative chemotherapies are combined with surgery.Human epidermal growth factor receptor 2(HER2)overexpression had been noted in gastric cancer;therefore,trastuzumab has been used occasionally in this setting.A 63-year-old male Chinese patient,who was diagnosed with adenocarcinoma in the gastric antrum,as well as lymph node metastases along the left gastric and hepatic artery,and left adrenal area,was admitted to our hospital.HER2 expression was positive,and cluster amplification was detected in a fluorescence in situ hybridization assay.The patient received three cycles of a neoadjuvant trastuzumab/oxaliplatin/capecitabine regimen.He subsequently underwent distal gastrectomy,D2+lymphadenectomy,left adrenalectomy,cholecystectomy and BillrothⅡanastomosis.Treatment was continued with another five postoperative cycles of the same medication and trastuzumab application for 1 year.No recurrence has been observed 18 mo after the operation.Trastuzumab as perioperative and adjuvant medication,in combination with oxaliplatin and capecitabine for a HER2-overexpressing advanced gastric adenocarcinoma,led to recurrence-free survival of at least 18 mo after surgery.
文摘Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug concentrations.Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy.The patient was treated with a combination of gemcitabine and oxaliplatin using HAI.The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI.The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper.HAI of gemcitabine-oxaliplatin should be evaluated in further clinical trials.
基金Supported by The National Outstanding Young Scientist Award of China, No. 30025016State Key Project for Basic Research, No. 30670956the Natural Science Foundation of Henan Province, China, No. 0511043200
文摘AIM:To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). METHODS: Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m2 po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m2 iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeat-ed for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed. RESULTS: The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ2 = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ2 = 0.032 and P = 0.857). Effi cacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ2 = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05). CONCLUSION: The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.
基金supported by the National Natural Science Foundation of China(81571781).
文摘Objective:To investigate the safety,efficacy,and prognostic factors of hepatic arterial infusion chemotherapy(HAIC)with raltitrexed and oxaliplatin post-transarterial chemoembolization(TACE)for unresectable hepatocellular carcinoma(uHCC).Methods:Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited.The primary endpoint was overall survival(OS),and secondary endpoint was progression-free survival(PFS).The overall response rate(ORR)was evaluated using the modified Response Evaluation Criteria in Solid Tumors.Toxicity was assessed according to the Common Terminology Criteria for Adverse Events(v4.0).The OS and prognostic factors were analyzed using the Kaplan-Meier method,log-rank test,and Cox regression models.Results:Three(8.1%)patients achieved complete response,17(46.0%)patients achieved partial response,and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months,respectively.The common toxicities included grade 3-4 increased aspartate aminotransferase levels(8/37,21.6%),grade 1-2 hyperbilirubinemia(75.7%,28/37),nonspecific abdominal pain and fever,and grade 2-3 thrombocytopenia(18.9%,7/37);no patients developed grade 3-4 neutropenia.Univariate analysis showed that the tumor diameter(≤50 mm,p=0.028),Barcelona Clinic Liver Cancer(BCLC)stage(p=0.012),hepatitis B virus DNA level(p=0.033),and derived neutrophil-to-lymphocyte ratio(dNLR;derived neutrophils/leukocytes minus neutrophils)(p=0.003)were predictive factors for prognosis.Multivariate analysis showed that patients with BCLC stage B disease(p=0.029)and dNLR<2 before therapy(p=0.004)had better prognosis.Conclusions:HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC;in particular,those with BCLC stage B and dNLR<2 have better prognosis.
基金supported by National Key R&D Program of China(2017YFA0505803)National Natural Science Foundation of China(No.81625017,No.81572385)National Science and Technology Major Project of China(2018ZX10302205).
文摘Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.
