Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase ...Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase A(LDHA)inhibitors can reduce the inflammation-induced effects,metastasis,and proliferation potential of cancer cells.Here,we adopt the water-in-oil attractive Pickering emulsion gel(APEG)to deliver OXA and LDHA inhibitor,GSK2837808A(GSK).OXA is dissolved in water and GSK is dissolved in iodized oil.This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly.OXA+GSK@gel has significant anti-tumor effect on HCC model,which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis.Meanwhile,flow analysis confirm that it could activate the tumor immune microenvironment in HCC.The infiltration of CD8^(+)T cells is increased,thereby providing better anti-tumor effect.The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.展开更多
BACKGROUND Drug-induced lung injury is a common adverse effect of chemotherapeutic agents.Diffuse alveolar hemorrhage(DAH)is a fatal complication associated with druginduced lung injury.Early diagnosis and treatment o...BACKGROUND Drug-induced lung injury is a common adverse effect of chemotherapeutic agents.Diffuse alveolar hemorrhage(DAH)is a fatal complication associated with druginduced lung injury.Early diagnosis and treatment of DAH is critical,as delayed management can lead to respiratory failure and poor outcomes.However,the diagnosis of DAH is difficult because of the nonspecific clinical manifestations;as such,bronchoscopy is necessary to establish a diagnosis.CASE SUMMARY The patient presented with fever and dry cough.He had been receiving fluoropyrimidine and oxaliplatin therapy for esophageal squamous cell carcinoma.Chest imaging revealed diffuse ground-glass opacities.Bronchoscopy with bronchoalveolar lavage was performed,which confirmed the diagnosis of DAH.Although the patient’s respiratory status rapidly worsened,high-dose corticosteroid therapy with respiratory support gradually improved the patient’s condition and he was successfully extubated.CONCLUSION Prompt DAH diagnosis and bronchoscopy in patients receiving oxaliplatincontaining chemotherapy presenting with acute respiratory failure are critical for improving outcomes.展开更多
BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological proce...BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological processes and various diseases,its role in gastric cancer(GC),particularly its expression and prognostic significance,remains poorly understood.In this study,we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC.Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.AIM To explore the expression of KRT80 in GC and its impact on the prognosis of patients.METHODS KRT80 expression in GC tissues was analyzed using Western blotting,quantitative reverse transcription PCR,multiple immunofluorescence staining,and immunohistochemistry.Survival analysis was conducted using the Kaplan-Meier method with the log-rank test.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1(EEF1A1)as a binding protein of KRT80.RESULTS Integrating our experimental findings with multiple published studies,we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin.Moreover,we have preliminarily verified the interaction between KRT80 and EEF1A1.Therefore,this study provides a novel perspective on overcoming oxaliplatin resistance in GC.CONCLUSION Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC,suggesting its potential as a novel prognostic biomarker.展开更多
Chiral anticancer drugs are the subject of ongoing research due to their optical characterization and pharmacological effects.Achieving a single enantiomer of a chiral anticancer drug is arduous,but it can significant...Chiral anticancer drugs are the subject of ongoing research due to their optical characterization and pharmacological effects.Achieving a single enantiomer of a chiral anticancer drug is arduous,but it can significantly improve its pharmacokinetics for tumor therapy.Here,the chiral nanocatchers,known as Dbiotin-P5■MCC NCs,were designed and prepared based on host-vip self-assembly between D-biotin anchored pillar[5]arene(D-biotin-P5)and myristoyl chloride choline(MCC).D-Biotin-P5■MCC NCs featuring the chiral separation and enzyme-induced disassemble were evaluated for their ability to selectively capture and subsequently target the release of(R,R)-OXA enantiomers into tumor cells.Furthermore,the use of D-biotin-P5■MCC NCs has demonstrated a significant enhancement in the intracellular uptake of OXA,with the drug being efficiently released to MCF-7 breast cancer cells.This has led to a superior inhibitory effect on MCF-7 cells when compared to free OXA,while also reducing the cytotoxicity of the drug in HEK 293 human embryonic kidney cells.This research not only paves a promising way for the fabrication of chiral supramolecular nanocarriers but also holds the potential to improve the processes of chiral drug separation and targeted therapy.展开更多
BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To stu...BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To study the effectiveness of in vitro chemosensitivity tests adenosine tripho-sphate-based tumour chemotherapy sensitivity test(ATP-TCA)for tailoring po-stoperative chemotherapy regimens for patients with CRC.METHODS Between January 2015 to December 2021,a total of 1549 CRC patients underwent surgery and in vitro chemosensitivity testing using ATP-TCA.A subset of 405 patients who met the survival assessment criteria were followed to collect data on overall survival(OS)and disease-free survival(DFS).Cox regression analysis revealed independent prognostic factors that affect OS and DFS for those re-ceiving oxaliplatin(L-OPH)and fluoropyrimidine-based regimens,aiding in the development of clinical predictive models.The relationships between the ATP-TCA results and clinical outcomes were analysed using the Kaplan-Meier method.RESULTS Tumour heterogeneity and resistance to multiple drugs were observed in 1549 patients.The sensitivity to 5-fluorouracil(5-FU)combined with L-OPH was tested among 1474 of these patients,yielding a sensitivity rate of 11.9%.ATP-TCA results were identified as an independent prognostic factor for DFS[P=0.002,hazard ratio(95%confidence interval):4.98(1.81-13.72)]in patients with resectable CRC.Compared with drug-resistant patients,sensitive CRC patients treated with 5-FU and L-OPH had significantly prolonged DFS(P=0.027).Further Kaplan-Meier analysis indicated that ATP-TCA sensitivity was significantly associated with improved OS(P=0.048)and DFS(P=0.003)in patients with stage III CRC.CONCLUSION The response of CRC patients to the combination regimen of 5-FU and L-OPH is heterogeneous.This study confirmed that the ATP-TCA is a valuable tool for predicting clinical outcomes,such as DFS,in patients with resectable CRC receiving chemotherapy.Although further validation with multicentre data is still necessary,these findings support that the ATP-TCA may function as a guiding tool for personalized chemotherapy administration,thereby optimizing treatment opportunities for patients.展开更多
BACKGROUND Gastric signet ring cell carcinoma(GSRC)is a distinctive type of gastric cancer.It is a mucus-secreting adenocarcinoma that may progress to distant metastasis at an early stage.Because of poor differentiati...BACKGROUND Gastric signet ring cell carcinoma(GSRC)is a distinctive type of gastric cancer.It is a mucus-secreting adenocarcinoma that may progress to distant metastasis at an early stage.Because of poor differentiation,aggressive invasion,rapid progre-ssion,and other high-risk characteristics,early surgical intervention should be prioritized.AIM To explore the clinical efficacy of fluorouracil(5-FU)combined with paclitaxel and oxaliplatin for the treatment of advanced GSRC.METHODS A total of 85 patients with advanced GSRC were selected between January 2020 and June 2021 and randomly divided into a control group(n=42,receiving standard chemotherapy)and a treatment group(n=43,receiving monotherapy with oxaliplatin,5-FU,and paclitaxel).Patients in the treatment group received a 135 mg/m2 infusion of paclitaxel for 3 hours,a 400 mg/m2 infusion of calcium folate(or 200 mg/m2 of levocalcium folate)for 2 hours,and an 85 mg/m2 infusion of oxaliplatin for 2 hours.This was followed by a continuous intravenous infusion of 2200-2400 mg/m25-FU for 46 hours using a portable pump.RESULTS The treatment group showed a median survival time of 11.7 months and an objective response rate(ORR)of 32.5%,significantly higher than the control group(P<0.05).Serum carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),and albumin levels were correlated with treatment effectiveness in advanced GSRC(P<0.01),but total serum protein was not correlated(P>0.05).Safety and survival were assessed in all patients.Short-term efficacy was evaluated in 66 patients,with a disease control rate of 89.4%and an ORR of 48.5%.Median progression-free survival was 7.0 months(95%confidence interval[CI]:6.85-7.15),and median overall survival was 10.6 months(95%CI:9.86-11.3).Primary grade III/IV adverse events included neutropenia(22.1%)and peripheral neurotoxicity(10.3%).CONCLUSION This treatment regimen is more effective for patients with advanced GSRC.Serum levels of CEA,CA19-9,and albumin predicted chemotherapy efficacy,while total protein concentration correlated minimally and insigni-ficantly.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)
Nuclear factor erythroid 2-related factor 2 （Nrf2） controls the expression of a wide array of antioxidant response element （ARE）-driven genes, which are involved in stress response and metabolism regulation. The r...Nuclear factor erythroid 2-related factor 2 （Nrf2） controls the expression of a wide array of antioxidant response element （ARE）-driven genes, which are involved in stress response and metabolism regulation. The role of Nrf2/ARE signaling in resistances of cancer cells to radiotherapy and chemotherapy has been widely accepted. However, much less is known about the relevance of Nrf2 to chemotherapy-associated toxicities, such as hepatotoxicity. In the present study, nine chemotherapeutic agents were firstly tested in embryonic fibroblasts （MEFs） and hepatocytes isolated from Nrf2 deficient or wild-type mice. The results indicate that the cytotoxicity of oxaliplatin in hepatocytes was significantly higher than that in MEFs and enhanced by Nrf2 deficiency. Furthermore, oxaliplatin treatment caused more pronounced steatosis and severer liver injury in Nrf2-/- mice compared with wild-type counterparts, as evidenced by dramatically elevated serum transaminase and bilirubin, increased accumulation of fat, inflammatory infiltration and blood congestion. The increased hepatotoxicity in Nrf2 deficient mice was possibly caused by decreased expression of antioxidant genes and glutathione depletion. Our results demonstrated that oxaliplatin-induced hepatotoxicity was significantly impacted by Nrf2 status, therefore Nrf2 could potentially serve as a biomarker to predict or a target to prevent hepatotoxicity of oxaliplatin.展开更多
To investigate whether microRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colorectal cancer (CRC) cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway.METHODSmiR-34a ex...To investigate whether microRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colorectal cancer (CRC) cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway.METHODSmiR-34a 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-34a 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.RESULTSExpression of miR-34a 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 miR-34a 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-34a in CRC patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in CRC cells.CONCLUSIONmiR-34a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-β/Smad4 pathway.展开更多
AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to...AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-fi ve patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m2) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m2) on day 1, and 2-3 h infusion of huachansu (20 mL/m2) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the fi rst, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response couldbe evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Non-hematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.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
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
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 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, oxa...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 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initial-ly 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 demon-strated 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 10 μM or 50 μM respectively as controls or combined with 20 mM NAD+. Treatment with 10 μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20 mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apop-totic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20 mM NAD+treatment great-ly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+provides signifi-cant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.展开更多
AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability w...AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay.Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Western blotting and immuno-precipitation were used to examine protein expression and recruitment,respectively.Nuclear factorκB(NFκB) binding activities were investigated using electrophoretic mobility shift assay.Nude mice were used to investigate tumor growth. RESULTS:Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibi-tion and cell apoptosis in vitro,and increased tumor growth inhibition and cell death in the tumor mass in vivo.In MKN45 and AGS cells,oxaliplatin treatment promoted both protein kinase B(Akt) and NFκB activation,while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NFκB binding.LY294002 promoted oxaliplatin-induced Fas ligand(FasL) expression,Fas-associated death domain protein recruitment,caspase-8,Bid,and caspase-3 activation,and the short form of cellular caspase-8/FLICEinhibitory protein(c-FLIPS) inhibition.In vivo,LY294002 inhibited oxaliplatin-induced activation of Akt and NFκB,and increased oxaliplatin-induced expression of FasL,inhibition of c-FLIPS,and activation of caspase-8,Bid,and caspase-3. CONCLUSION:Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer treatment.The enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway.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 r...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 Billroth II anastomosis. 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
基金supported by Natural Science Foundation of Zhejiang Province(Nos.LY20H160033,LY22H160019)National Key Research and Development Program of China(No.YS2021YFC3000089)+1 种基金Zhejiang Province Science and Technology Plan Project(No.2024C03175)National Natural Science Foundation of China(Nos.82074208,22278352,82473004).
文摘Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase A(LDHA)inhibitors can reduce the inflammation-induced effects,metastasis,and proliferation potential of cancer cells.Here,we adopt the water-in-oil attractive Pickering emulsion gel(APEG)to deliver OXA and LDHA inhibitor,GSK2837808A(GSK).OXA is dissolved in water and GSK is dissolved in iodized oil.This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly.OXA+GSK@gel has significant anti-tumor effect on HCC model,which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis.Meanwhile,flow analysis confirm that it could activate the tumor immune microenvironment in HCC.The infiltration of CD8^(+)T cells is increased,thereby providing better anti-tumor effect.The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.
文摘BACKGROUND Drug-induced lung injury is a common adverse effect of chemotherapeutic agents.Diffuse alveolar hemorrhage(DAH)is a fatal complication associated with druginduced lung injury.Early diagnosis and treatment of DAH is critical,as delayed management can lead to respiratory failure and poor outcomes.However,the diagnosis of DAH is difficult because of the nonspecific clinical manifestations;as such,bronchoscopy is necessary to establish a diagnosis.CASE SUMMARY The patient presented with fever and dry cough.He had been receiving fluoropyrimidine and oxaliplatin therapy for esophageal squamous cell carcinoma.Chest imaging revealed diffuse ground-glass opacities.Bronchoscopy with bronchoalveolar lavage was performed,which confirmed the diagnosis of DAH.Although the patient’s respiratory status rapidly worsened,high-dose corticosteroid therapy with respiratory support gradually improved the patient’s condition and he was successfully extubated.CONCLUSION Prompt DAH diagnosis and bronchoscopy in patients receiving oxaliplatincontaining chemotherapy presenting with acute respiratory failure are critical for improving outcomes.
基金Supported by National Natural Science Foundation of China,No.874063.
文摘BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological processes and various diseases,its role in gastric cancer(GC),particularly its expression and prognostic significance,remains poorly understood.In this study,we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC.Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.AIM To explore the expression of KRT80 in GC and its impact on the prognosis of patients.METHODS KRT80 expression in GC tissues was analyzed using Western blotting,quantitative reverse transcription PCR,multiple immunofluorescence staining,and immunohistochemistry.Survival analysis was conducted using the Kaplan-Meier method with the log-rank test.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1(EEF1A1)as a binding protein of KRT80.RESULTS Integrating our experimental findings with multiple published studies,we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin.Moreover,we have preliminarily verified the interaction between KRT80 and EEF1A1.Therefore,this study provides a novel perspective on overcoming oxaliplatin resistance in GC.CONCLUSION Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC,suggesting its potential as a novel prognostic biomarker.
基金supported by the National Natural Science Foundations of China(Nos.22464022,22461048,and 22364023)Scientific Research Fund Project of Yunnan Education Department(No.2023j0204)+3 种基金Yunnan Normal University Doctoral Research Initiation Program(No.01100205020503180)Xing Dian Talent Support Program Foundations(No.01100208019916016)Yunnan Normal University Graduate Research Innovation Fund Project(No.YJSJJ23-B87)Yunnan Basic Research Funding Program(Nos.202401AT070128,202301AT070074,and 202201AU070056)。
文摘Chiral anticancer drugs are the subject of ongoing research due to their optical characterization and pharmacological effects.Achieving a single enantiomer of a chiral anticancer drug is arduous,but it can significantly improve its pharmacokinetics for tumor therapy.Here,the chiral nanocatchers,known as Dbiotin-P5■MCC NCs,were designed and prepared based on host-vip self-assembly between D-biotin anchored pillar[5]arene(D-biotin-P5)and myristoyl chloride choline(MCC).D-Biotin-P5■MCC NCs featuring the chiral separation and enzyme-induced disassemble were evaluated for their ability to selectively capture and subsequently target the release of(R,R)-OXA enantiomers into tumor cells.Furthermore,the use of D-biotin-P5■MCC NCs has demonstrated a significant enhancement in the intracellular uptake of OXA,with the drug being efficiently released to MCF-7 breast cancer cells.This has led to a superior inhibitory effect on MCF-7 cells when compared to free OXA,while also reducing the cytotoxicity of the drug in HEK 293 human embryonic kidney cells.This research not only paves a promising way for the fabrication of chiral supramolecular nanocarriers but also holds the potential to improve the processes of chiral drug separation and targeted therapy.
基金Supported by the National Natural Science Foundation of China,No.U24A20765 and No.T2321005Jiangsu Provincial Science and Technology Plan Special Fund,No.BM2023003+5 种基金Jiangsu Provincial Medical Key Discipline,No.ZDXK202247the Priority Academic Program Development of the Jiangsu Higher Education InstitutesJiangsu Engineering Research Center on Drug Evaluation and Translation of Organoids/Organ Chip(2024)the Science and Technology Plan of Suzhou,No.SKYD2023183the Research Project Established by Chinese Pharmaceutical Association Hospital Pharmacy Department,No.CPA-Z05-ZC-2023002Gusu Health Talent Research Project,No.GSWS2022015.
文摘BACKGROUND Chemotherapy is an essential treatment for colorectal cancer(CRC)patients after surgery,but many patients do not benefit from chemotherapy because tumour heterogeneity results in varied responses.AIM To study the effectiveness of in vitro chemosensitivity tests adenosine tripho-sphate-based tumour chemotherapy sensitivity test(ATP-TCA)for tailoring po-stoperative chemotherapy regimens for patients with CRC.METHODS Between January 2015 to December 2021,a total of 1549 CRC patients underwent surgery and in vitro chemosensitivity testing using ATP-TCA.A subset of 405 patients who met the survival assessment criteria were followed to collect data on overall survival(OS)and disease-free survival(DFS).Cox regression analysis revealed independent prognostic factors that affect OS and DFS for those re-ceiving oxaliplatin(L-OPH)and fluoropyrimidine-based regimens,aiding in the development of clinical predictive models.The relationships between the ATP-TCA results and clinical outcomes were analysed using the Kaplan-Meier method.RESULTS Tumour heterogeneity and resistance to multiple drugs were observed in 1549 patients.The sensitivity to 5-fluorouracil(5-FU)combined with L-OPH was tested among 1474 of these patients,yielding a sensitivity rate of 11.9%.ATP-TCA results were identified as an independent prognostic factor for DFS[P=0.002,hazard ratio(95%confidence interval):4.98(1.81-13.72)]in patients with resectable CRC.Compared with drug-resistant patients,sensitive CRC patients treated with 5-FU and L-OPH had significantly prolonged DFS(P=0.027).Further Kaplan-Meier analysis indicated that ATP-TCA sensitivity was significantly associated with improved OS(P=0.048)and DFS(P=0.003)in patients with stage III CRC.CONCLUSION The response of CRC patients to the combination regimen of 5-FU and L-OPH is heterogeneous.This study confirmed that the ATP-TCA is a valuable tool for predicting clinical outcomes,such as DFS,in patients with resectable CRC receiving chemotherapy.Although further validation with multicentre data is still necessary,these findings support that the ATP-TCA may function as a guiding tool for personalized chemotherapy administration,thereby optimizing treatment opportunities for patients.
文摘BACKGROUND Gastric signet ring cell carcinoma(GSRC)is a distinctive type of gastric cancer.It is a mucus-secreting adenocarcinoma that may progress to distant metastasis at an early stage.Because of poor differentiation,aggressive invasion,rapid progre-ssion,and other high-risk characteristics,early surgical intervention should be prioritized.AIM To explore the clinical efficacy of fluorouracil(5-FU)combined with paclitaxel and oxaliplatin for the treatment of advanced GSRC.METHODS A total of 85 patients with advanced GSRC were selected between January 2020 and June 2021 and randomly divided into a control group(n=42,receiving standard chemotherapy)and a treatment group(n=43,receiving monotherapy with oxaliplatin,5-FU,and paclitaxel).Patients in the treatment group received a 135 mg/m2 infusion of paclitaxel for 3 hours,a 400 mg/m2 infusion of calcium folate(or 200 mg/m2 of levocalcium folate)for 2 hours,and an 85 mg/m2 infusion of oxaliplatin for 2 hours.This was followed by a continuous intravenous infusion of 2200-2400 mg/m25-FU for 46 hours using a portable pump.RESULTS The treatment group showed a median survival time of 11.7 months and an objective response rate(ORR)of 32.5%,significantly higher than the control group(P<0.05).Serum carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),and albumin levels were correlated with treatment effectiveness in advanced GSRC(P<0.01),but total serum protein was not correlated(P>0.05).Safety and survival were assessed in all patients.Short-term efficacy was evaluated in 66 patients,with a disease control rate of 89.4%and an ORR of 48.5%.Median progression-free survival was 7.0 months(95%confidence interval[CI]:6.85-7.15),and median overall survival was 10.6 months(95%CI:9.86-11.3).Primary grade III/IV adverse events included neutropenia(22.1%)and peripheral neurotoxicity(10.3%).CONCLUSION This treatment regimen is more effective for patients with advanced GSRC.Serum levels of CEA,CA19-9,and albumin predicted chemotherapy efficacy,while total protein concentration correlated minimally and insigni-ficantly.
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National Natural Science Foundation of China(Grant No.81272468,81372266,91429305 and 21001011)WU JIEPING Medical Foundation(Grant No.320.6750.12196)
文摘Nuclear factor erythroid 2-related factor 2 （Nrf2） controls the expression of a wide array of antioxidant response element （ARE）-driven genes, which are involved in stress response and metabolism regulation. The role of Nrf2/ARE signaling in resistances of cancer cells to radiotherapy and chemotherapy has been widely accepted. However, much less is known about the relevance of Nrf2 to chemotherapy-associated toxicities, such as hepatotoxicity. In the present study, nine chemotherapeutic agents were firstly tested in embryonic fibroblasts （MEFs） and hepatocytes isolated from Nrf2 deficient or wild-type mice. The results indicate that the cytotoxicity of oxaliplatin in hepatocytes was significantly higher than that in MEFs and enhanced by Nrf2 deficiency. Furthermore, oxaliplatin treatment caused more pronounced steatosis and severer liver injury in Nrf2-/- mice compared with wild-type counterparts, as evidenced by dramatically elevated serum transaminase and bilirubin, increased accumulation of fat, inflammatory infiltration and blood congestion. The increased hepatotoxicity in Nrf2 deficient mice was possibly caused by decreased expression of antioxidant genes and glutathione depletion. Our results demonstrated that oxaliplatin-induced hepatotoxicity was significantly impacted by Nrf2 status, therefore Nrf2 could potentially serve as a biomarker to predict or a target to prevent hepatotoxicity of oxaliplatin.
基金Supported by Science Foundation of Education Department of Heilongjiang Province,China,no.12541430
文摘To investigate whether microRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colorectal cancer (CRC) cells by inhibiting macroautophagy via the transforming growth factor (TGF)-β/Smad4 pathway.METHODSmiR-34a 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-34a 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.RESULTSExpression of miR-34a 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 miR-34a 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-34a in CRC patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-β/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in CRC cells.CONCLUSIONmiR-34a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-β/Smad4 pathway.
文摘AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-fi ve patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m2) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m2) on day 1, and 2-3 h infusion of huachansu (20 mL/m2) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the fi rst, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response couldbe evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Non-hematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.
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.
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.
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Supported by The Guangdong Provincial Science and Technology Programs,China,No.2009A030301013the Scientific Funds of Guangzhou Medical College,China,No.2010A29+1 种基金National Natural Science Foundation of China,No.30700398 and 81172831Natural Science Foundation of Guangdong Province,No.10151008901000200
文摘AIM： To observe the synergistic effects of hyperthermia in oxaliplatin-induced cytotoxicity in human colon adenocarcinoma Lovo cells.
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 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initial-ly 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 demon-strated 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 10 μM or 50 μM respectively as controls or combined with 20 mM NAD+. Treatment with 10 μM oxaliplatin for 48 hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20 mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apop-totic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20 mM NAD+treatment great-ly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+provides signifi-cant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.
基金Supported by The National Natural Science Foundation of China,No.30470782
文摘AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay.Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Western blotting and immuno-precipitation were used to examine protein expression and recruitment,respectively.Nuclear factorκB(NFκB) binding activities were investigated using electrophoretic mobility shift assay.Nude mice were used to investigate tumor growth. RESULTS:Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibi-tion and cell apoptosis in vitro,and increased tumor growth inhibition and cell death in the tumor mass in vivo.In MKN45 and AGS cells,oxaliplatin treatment promoted both protein kinase B(Akt) and NFκB activation,while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NFκB binding.LY294002 promoted oxaliplatin-induced Fas ligand(FasL) expression,Fas-associated death domain protein recruitment,caspase-8,Bid,and caspase-3 activation,and the short form of cellular caspase-8/FLICEinhibitory protein(c-FLIPS) inhibition.In vivo,LY294002 inhibited oxaliplatin-induced activation of Akt and NFκB,and increased oxaliplatin-induced expression of FasL,inhibition of c-FLIPS,and activation of caspase-8,Bid,and caspase-3. CONCLUSION:Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer treatment.The enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway.
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 Billroth II anastomosis. 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.
