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| 1 | Expressions of Thymidylate Synthase, Thymidine Phosphorylase, Class Ⅲ β-tubulin, and Excision Repair Cross-complementing Group 1 Predict Response in Advanced Gastric Cancer Patients Receiving Capecitabine Plus Paclitaxel or Cisplatin显示文摘Objective: To evaluate the role of class III β-tubulin (TUBB3), thymidylate synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementing group 1 (ERCC1) in clinical outcome of advanced gastric cancer patients receiving capecitabine plus paclitaxel or cisplatin. Methods: The clinical data and tumor specimens from 57 advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel (cohort 1, n=36) and capecitabine plus cisplatin (cohort 2, n=21) were retrospectively collected, and TUBB3, TS, TP, and ERCC1 expressions were detected by real-time quantitative PCR. The associations between expressions of biomarkers and response or survival were analyzed statistically. Results: The median age of 57 patients was 57 years (range: 27-75 years) with 38 males and 19 females. Of all patients, the response rates of patients with high TP, low TP and high TS, low TS expressions were 57.1%, 27.6% (P=0.024), and 55.2%, 28.6% (P=0.042), respectively. Among cohort 1, the response rates and median overall survivals of patients with low and high TUBB3 expressions were 61.1% vs. 33.3% (P=0.095) and 13.8 months vs. 6.6 months (P=0.019), respectively; the response rate (87.5%) of patients with low TUBB3 and high TP expressions was higher than that (14.3%) of patients with high TUBB3 and low TP expressions (P=0.01). Among cohort 2, the response rates of patients with low ERCC1 and high ERCC1 expressions were 45.5% and 20.0% respectively (P=0.361). Conclusion: TUBB3, TS and TP expressions could predict the response of advanced gastric cancer patients receiving capecitabine-based and paclitaxel-based chemotherapy. These results will be further confirmed in future large samples. | Ming Lu Jing Gao Xi-cheng Wang Lin Shen | 2011 | Chinese Journal of Cancer Research2011，23，4： | 22 |
| 2 | Nedaplatin concurrent with three-dimensional conformal radiotherapy for treatment of locally advanced esophageal carcinoma显示文摘AIM:To evaluate the efficacy and toxicity of nedaplatin(NDP)concurrent with radiotherapy in the treatment of locally advanced esophageal carcinoma.METHODS:Sixty-eight patients with locally advanced esophageal carcinoma were randomized into either a NDP group(n=34)or a cisplatin(DDP)group(n=34).The NDP group received NDP 80-100 mg/m2iv on day 1+leucovorin(CF)100 mg/m2iv on days 1-5+5-fluorouracil(5-FU)500 mg/m2iv on days 1-5.The DDP group received DDP 30 mg/m2iv on days 1-3+CF 100 mg/m2on days 1-5+5-FU 500 mg/m2iv on days 1-5.The treatment was repeated every 4 wk in both groups.Concurrent radiotherapy[60-66 Gy/(30-33f)/(6-7 wk)]was given during chemotherapy.RESULTS:There was no significant difference in the short-term response rate between the NDP group and DDP group(90.9%vs 81.3%,P=0.528).Although the 1-and 2-year survival rates were higher in the NDP group than in the DDP group(75.8%vs 68.8%,57.6%vs 50.0%),the difference in the overall survival rate was not statistically significant between the two groups(P=0.540).The incidences of nausea,vomiting and nephrotoxicity were significantly lower in the NDP group than in the DDP group(17.6%vs 50.0%,P=0.031;11.8%vs 47.1%,P=0.016;8.8%vs 38.2%,P=0.039).There was no significant difference in the incidence of myelosuppression,radiation-induced esophagitis or radiation-induced pneumonia between the two groups.CONCLUSION:NDP-based concurrent chemoradiotherapy is effective and well-tolerated in patients with locally advanced esophageal carcinoma.NDP-based regimen has comparable efficacy to DDP-based regimen but is associated with lower incidences of gastrointestinal and renal toxicity. | Ze-Tian Shen Xin-Hu Wu Bing Li Jun-Shu Shen Zhen Wang Jing Li Xi-Xu Zhu | 2013 | World Journal of Gastroenterology2013，19，48： | 23 |
| 3 | Malignant peritoneal mesothelioma显示文摘Malignant mesothelioma is a highly aggressive neoplasm.The incidence of malignant mesothelioma is increasing worldwide.Diffuse malignant peritoneal mesothelioma(DMPM) represents one-fourth of all mesotheliomas.Association of asbestos exposure with DMPM has been observed,especially in males.The great majority of patients present with abdominal pain and distension,caused by accumulation of tumors and ascitic ? uid.In the past,DMPM was considered a pre-terminal condition;therefore attracted little attention.Patients invariably died from their disease within a year.Recently,several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy.This remarkable improvement in survival has prompted new search into the medical science related to DMPM,a disease previously ignored as uninteresting.This review article focuses on the key advances in the epidemiology,diagnosis,staging,treatments and prognosis of DMPM that have occurred in the past decade. | Stine Munkholm-Larsen Christopher Q Cao Tristan D Yan | 2009 | World Journal of Gastrointestinal Surgery2009，1，1： | 19 |
| 4 | Pericardiocentesis with cisplatin for malignant pericardial effusion and tamponade显示文摘AIM:To evaluate the role and outcome of pericardiocentesis with intrapericardial cisplatin instillation for malignant pericardial effusion resulting from esophageal cancer. METHODS:We retrospectively studied 7 patients who underwent pericardiocentesis with intrapericardial cisplatin instillation for malignant pericardial effusion resulting from esophageal cancer.After pericardiocentesis,we performed catheterization of the pericardial space under ultrasonogram guidance.Malignant etiology of the pericardial fluid was confirmed by cytological examination.Subsequently,cisplatin(10 mg in 20 mL normal saline) was instilled into the pericardial space. RESULTS:The mean total volume of the aspirated effusion fluid was 782±264 mL(range,400-1200 mL) . The drainage catheter was successfully removed in all patients,and the mean duration of pericardial drainagewas 7.7±2.7 d(range,5-13 d) .No fluid reaccumulation was observed.Mean survival time was 120±71 d(range,68-268 d) . CONCLUSION:Pericardiocentesis along with catheter drainage appears to be a safe and effective for pericardial malignant effusion and tamponade,and cisplatin instillation prevents recurrence. | Takatsugu Oida Kenji Mimatsu Hiso Kano Atsushi Kawasaki Youichi Kuboi Nobutada Fukino Sadao Amano | 2010 | World Journal of Gastroenterology2010，16，6： | 19 |
| 5 | Long-term outcomes of a phase Ⅱ randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma显示文摘Background:Salvage treatment for locally recurrent nasopharyngeal carcinoma(NPC) is complicated and relatively limited.Radiotherapy,combined with effective concomitant chemotherapy,may improve clinical treatment outcomes.We conducted a phase Ⅱ randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.Methods:Between April 2002 and January 2008,69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group(n = 34) or radiotherapy alone group(n = 35).All patients received intensity-modulated radiotherapy.The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days(range 23-53 days).The concomitant chemotherapy schedule was cisplatin 30 mg/m^2 by intravenous infusion weekly during radiotherapy.Results:The median follow-up period of all patients was 35 months(range 2-112 months).Between concomitant chemoradiotherapy and radiotherapy groups,there was only significant difference in the 3-year and 5-year overall survival(OS) rates(68.7%vs.42.2%,P = 0.016 and 41.8%vs.27.5%,P = 0.049,respectively).Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4(33.0%vs.13.2%,P = 0.009),stages Ⅲ-Ⅳ(34.3%vs.13.2%,P = 0.006),recurrence interval >30 months(49.0%vs.20.6%,P = 0.017),and tumor volume >26 cm^3(37.6%vs.0%,P = 0.006).Conclusion:Compared with radiotherapy alone,concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC,especially those with advanced T category(rT3-4) and stage(lll-IV) diseases,recurrence intervals >30 months,and tumor volume >26 cm^3. | Ying Guan Shuai Liu Han-Yu Wang Ying Guo Wei-Wei Xiao Chun-Yan Chen Chong Zhao Tai-Xiang Lu Fei Han | 2016 | Chinese Journal of Cancer2016，35，4： | 19 |
| 6 | 康莱特注射液诱导肝癌细胞凋亡及其对凋亡蛋白procaspase-3和caspase-9表达的影响显示文摘目的:探讨康莱特注射液(Kanglaite)对人肝癌BEL-7404细胞的增殖抑制作用、凋亡诱导作用以及对凋亡蛋白pro-caspase-3和caspase-9表达的影响。方法:采用MTT法检测康莱特注射液和阳性对照顺铂(cisplatin,DDP)对BEL-7404细胞的增殖抑制作用,Hoechst33258染色观察凋亡细胞核的情况,FCM检测细胞凋亡率,Western印迹法检测凋亡蛋白procaspase-3和caspase-9的表达。结果:MTT结果显示,经不同体积浓度康莱特注射液(10、20、40、80及160μL/mL)作用BEL-7404细胞后,80μL/mL康莱特注射液作用48 h时对肝癌BEL-7404细胞有明显的抑制增殖作用;Hoechst 33258染色可见细胞出现典型的凋亡细胞形态学改变;FCM法检测结果提示,空白对照组、DDP 10μg/mL组和康莱特注射液80μL/mL组的凋亡率分别为(1.23±0.40)%、(32.53±0.65)%和(3.13±0.32)%(P<0.01);Western印迹法检测结果提示,康莱特注射液及DDP作用48 h后procaspase-3蛋白的表达量明显降低(P<0.01),caspase-9蛋白的表达量显著升高(P<0.01)。结论:康莱特注射液可抑制肝癌BEL-7404细胞增殖并诱导其凋亡,其作用机制可能与凋亡相关蛋白procaspase-3表达下调及caspase-9表达上调有关。 | 李海军 王辉 方全华 张国庆 | 2010 | 肿瘤2010，30，9： | 18 |
| 7 | Establishment of a human hepatoma multidrug resistant cell line in vitro显示文摘AIM:To establish a multidrug-resistant hepatoma cell line(SK-Hep-1),and to investigate its biological characteristics.METHODS:A highly invasive SK-Hep-1 cell line of human hepatocellular carcinoma,also known as malignant hepatoma was incubated with a high concentration of cisplatin(CDDP) to establish a CDDP-resistant cell subline(SK-Hep-1/CDDP).The 50% inhibitory dose(IC50) values and the resistance indexes [(IC50 SK-Hep-1/CDDP)/(IC50 SK-Hep-1)] for other chemotherapeutic agents and the growth curve of cells were all evaluated using cell counting kit-8 assays.The distribution of the cell cycles were detected by flow cytometry.Expression of acquired multidrug resistance P-glycoprotein(MDR1,ABCB1) and multidrug resistance-associated protein 1(MRP1,ABCC1) was compared with that in parent cells by Western blotting and immunofluorescence combined with laser scanning confocal microscopy.RESULTS:The SK-Hep-1/CDDP cells(IC50 = 70.61 ± 1.06 μg/mL) was 13.76 times more resistant to CDDP than the SK-Hep-1 cells(IC50 = 5.13 ± 0.09 μg/mL),and CDDP-resistant cells also demonstrated cross-resistance to many anti-tumor agents such as doxorubicin,5-fluorouracil and vincristine.Similar morphologies were determined in both SK-Hep-1 and SK-Hep-1/CDDP groups.The cell cycle distribution of the SK-Hep-1/CDDP cell line exhibited a significantly increased percentage of cells in S(42.2% ± 2.65% vs 27.91% ± 2.16%,P < 0.01) and G2/M(20.67% ± 5.69% vs 12.14% ± 3.36%,P < 0.01) phases in comparison with SK-Hep-1 cells,while the percentage of cells in the G0/G1 phase decreased(37.5% ± 5.05% vs 59.83% ± 3.28%,P < 0.01).The levels of MDR1 and MRP1 were overexpressed in the SK-Hep-1/CDDP cells exhibiting the MDR phenotype.CONCLUSION:Multiple drug resistance of multiple drugs in the human hepatoma cell line SK-Hep-1/CDDP was closely related to the overexpression of MDR1 and MRP1. | Zhou, Yuan Ling, Xian-Long Li, Shi-Wei Li, Xin-Qiang Yan, Bin | 2010 | World Journal of Gastroenterology2010，16，18： | 17 |
| 8 | A pharmacological review on intraperitoneal chemotherapy for peritoneal malignancy显示文摘Perioperative intraperitoneal chemotherapy in combination with cytoreductive surgery has been shown to be of benefit for treating selected patients with peritoneal surface malignancy.It has become a new standard of care in the management of diffuse malignant peritoneal mesothelioma and peritoneal dissemination of appendiceal malignancy.Numerous recent publications on carcinomatosis from colorectal cancer and gastric cancer identify groups of patients that would benef it from this local-regional approach for prevention and treatment of carcinomatosis.This review focuses on pharmacological information regarding intraperitoneal chemotherapeutic agents commonly used in gastrointestinal oncology. | Tristan D Yan Christopher Qian Cao Stine Munkholm-Larsen | 2010 | World Journal of Gastrointestinal Oncology2010，2，2： | 14 |
| 9 | Platinum-induced neurotoxicity: A review of possible mechanisms显示文摘Patients treated with platinum-based chemotherapy frequently experience neurotoxic symptoms, which may lead to premature discontinuation of therapy. Despitediscontinuation of platinum drugs, these symptoms can persist over a long period of time. Cisplatin and oxaliplatin, among all platinum drugs, have significant neurotoxic potential. A distal dose-dependent symmetrical sensory neuropathy is the most common presentation of platinum neurotoxicity. DNA damage-induced apoptosis of dorsal root ganglion(DRG) neurons seems to be the principal cause of neurological symptoms. However, DRG injury alone cannot explain some unique symptoms such as cold-aggravated burning pain affecting distal extremities that is observed with oxaliplatin administration. In this article, we briefly reviewed potential mechanisms for the development of platinum drugs-associated neurological manifestations. | Ozkan Kanat Hulya Ertas Burcu Caner | 2017 | World Journal of Clinical Oncology2017，8，4： | 14 |
| 10 | The preparation and characterization of folate-conjugated human serum albumin magnetic cisplatin nanoparticles显示文摘Objective:Nanoparticles are becoming an important method of targeted drug delivery.To evaluate the importance of folate-conjugated human serum albumin(HSA)magnetic nanoparticles(Folate-CDDP/HSA MNP),we prepared drug-loaded Folate-CDDP/HSA MNPs and characterized their features.Methods:First, folate was conjugated with HSA under the effect of a condensing agent,and the conjugating rate was evaluated by a colorimetric method using 2,4,6-trinitrobenzene sulfonic acid.Second,under N 2 gas,Fe 3 O 4 magnetic nanomaterials were prepared and characterized by using transmission electron microscopy(TEM),SEM-EDS and X-ray diffraction(XRD).Finally,Folate-CDDP/HSA MNP was prepared by using a solvent evaporation technique. TEM was used to observe particle morphology.The particle size and distribution of the prepared complexes were determined by a Laser particle size analyzer.Drug loading volume and drug release were investigated by a high performance liquid chromatography method(HPLC)in vitro.Results:We successfully prepared folate-conjugated HSA and its conjugating rate was 27.26μg/mg.Under TEM,Fe 3 O 4 magnetic nanoparticles were highly electron density and had an even size distribution in the range of 10-20 nm.It was confirmed by SEM-EDS and XRD that Fe 3 O 4 magnetic nanoparticles had been successfully prepared.Under TEM,drug-loaded magnetic nanoparticles were observed,which had a round shape,similar uniform size and smooth surface.Their average size was 79 nm which was determined by laser scattering,and they exhibited magnetic responsiveness.Encapsulation efficiency was 89.75%and effective drug loading was calculated to be 15.25%.The release results in vitro showed that the half release time(t1/ 2 )of cisplatin in cisplatin Solution and Folate-CDDP/HSA MNP was 65 min and 24 h respectively, which indicated that microspheres had an obvious effect of sustained-release.Conclusion:Folate-CDDP/HSA MNPs were prepared successfully.The preparation process and related characteristics data provided a foundation for further study,including the mechanism of the nanoparticles distribution in vivo and their intake by tumor cells. | Daozhen Chen Qiusha Tang Wenqun Xue Jingying Xiang Li Zhang Xinru Wang | 2010 | The Journal of Biomedical Research2010，24，1： | 13 |
| 11 | Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells显示文摘Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary(Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC(Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8^+T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC(myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8^+T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin. | LIU Wen WU Tian-Cong HONG Dong-Mei HU Yue FAN Ting GUO Wen-Jie XU Qiang | 2018 | Chinese Journal of Natural Medicines2018，16，12： | 11 |
| 12 | Modulation of copper transporters in protection against cisplatin-induced cochlear hair cell damage显示文摘Cisplatin belongs to platinum-based drugs and is widely used in cancer chemotherapy.Ototoxicity is one of the major dose limiting side-effects of cisplatin.For toxicity to occur cisplatin must first be transported from the bloodstream into cochlear cells.Three copper transporters are considered pathways for regulating the uptake and translocation of cisplatin into cells:Ctr1,ATP7A and ATP7B.Our recent study with cochlear organotypic cultures shows that cochlear hair cells can be destroyed by cisplatin at low concentrations from 10μm to 100μn.However,high doses of cisplatin cannot damage hair cells,maybe due to intrinsic feedback reactions that increase export of platinum by ATP7B when the platinum concentration is high in extracellular space.Cimitidine is a specific copper transporter inhibitor that can block the entrance of copper and platinum,and may prevent cisplatin-induced cochlear hair cell injury.To evaluate this hypothesis,we treated cochlear organotypic cultures with cisplatin (10 μm or 50 μm) alone,or cisplatin combined with cimitidine at concentrations ranging from 10-2000 μm for 48 hours.cisplatin at 10 μm damaged about 20% hair cells.In contrast,when cimitidine (10 μm,100 μm and 2000 μm) was added to the culture,near 100% cochlear hair cell survived.At higher concentration (50 μm),cisplatin destroyed about 80% of cochlear hair cells.However,100 μmcimitidine rescued about 50% hair cells from cisplatin damage,and 2000μm cimitidine protected about 80% hair cells.The data of western blot showed that CTR1 and ATP7B expressions were increased in cisplatin treated cochlear tissue,but cimitidine significantly reduced CTR1 and ATP7B.In addition,ATP7A expression was depressed a little after cisplatin treatment.Considering that Ctr1 is involved in copper and platinum influx,but the ATP7A and ATP7B are copper export transporters,the results suggest that cimitidine can effectively block the entrance by copper transporters and stop the influx of cisplatin. | Richard Salvi | 2011 | Journal of Otology2011，6，2： | 10 |
| 13 | Antitumor effect of recombinant human endostatin combined with cisplatin on rats with transplanted Lewis lung cancer显示文摘Objective: To observe the antitumor effect and mechanism of recombinant human endostatin(Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg.kg-1.d for 10 d. Group C was given the injection of Endostar 5 mg.kg-1.d combined with intraperitoneal injection of cisplatin 5 mg.kg-1.d for 10 d. All the rats in three groups were executed the day after the 10-d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor(VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density(MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A(P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B(P < 0.05). The antitumor rate in Group C was significantly higher than Group B(P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B(P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A(P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect. | Zhan-Wu Yu Ying-Hua Ju Cheng-Liang Yang Han-Bing Yu Quan Luo Ye-Gang Ma Yong-Yu Liu | 2015 | Asian Pacific Journal of Tropical Medicine2015，8，8： | 10 |
| 14 | ECRG2 enhances the anti-cancer effects of cisplatin in cisplatin-resistant esophageal cancer cells via upregulation of p53 and downregulation of PNCA显示文摘AIM To explore the anti-tumor effects of esophageal cancerrelated gene 2(ECRG2) in combination with cisplatin(DDP) in DDP-resistant esophageal cancer cells(EC9706/DDP).METHODS A drug-resistant cell model was established, with EC9706/DDP cells being treated with ECRG2 and/or DDP. Cell viability was examined by MTT assay. The rate of cell apoptosis was determined by flow cytometry. The mR NA expression levels of proliferating cell nuclear antigen(PCNA), metallothionein(MT), and p53 were determined by RT-PCR and PCNA, while MT and p53 protein expression levels were determined by western blotting.RESULTS The anti-proliferative effect of ECRG2 in combination with DDP was superior when compared to ECRG2 or DDP alone. The inhibition rate for the combination reached its peak(51.33%) at 96 h. The early apoptotic rates of the control, ECRG2 alone, DDP alone, and ECRG2 plus DDP groups were 5.71% ± 0.27%, 12.68% ± 0.61%, 14.15% ± 0.87%, and 27.96% ±0.36%, respectively. Although all treatment groups were significantly different from the control group(P < 0.05), the combination treatment of ECRG2 plus DDP performed significantly better when compared to either ECRG2 or DDP alone(P < 0.05). The combination of ECRG2 and DDP significantly upregulated p53 m RNA and protein levels and downregulated PCNA m RNA and protein levels compared to ECRG2 or DDP alone(P < 0.05). However, no changes were seen in the expression of MT mR NA or protein.CONCLUSION ECRG2 in combination with DDP can inhibit viability and induce apoptosis in esophageal cancer DDP-resistant cells, possibly via upregulation of p53 expression and downregulation of PCNA expression. These findings suggest that the combination of ECRG2 and DDP may be a promising strategy for the clinical treatment of esophageal cancers that are resistant to DDP. | Xin-Fang Hou Lin-Ping Xu Hai-Yan Song Shuai Li Chen Wu Ju-Feng Wang | 2017 | World Journal of Gastroenterology2017，23，10： | 10 |
| 15 | Effect of tetramethylpyrazin combined with cisplatin on VEGF,KLF4 and ADAMTS1 in lewis lung cancer mice显示文摘Objective: To further explore the function of combine use of tetramethylpyrazine(TMP) and cisplatin(DDP) in lung carcinoma. Methods: We used the combination drug to treat Lewis lung cancer mice, investigated the expression level of vascular endothelial growth factor(VEGF), Kruppel-like factor 4(KLF4) and A disintegrin and metalloproteinase with thrombospondin motifs 1(ADAMTS1) and to further explore the inhibitory effects and potential mechanism of TMP combined with DDP on tumor angiogenesis. Results: The tumor growth was suppressed in TMP group, DDP group and TMP combined with DDP group. Furthermore, the weights and volume of tumor, the expression level of VEGF, KLF4 and ADAMTS1 were found significantly changed between experiment group and control group. These findings suggest that TMP with DDP had additional or synergistic effects to inhibit the tumor growth effectively, might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expression of angiogenesis inhibitors KLF4 and ADAMTS1. Conclusion: KLF4 and ADAMTS1 may be synergically involved in the angiogenesis in mouse Lewis lung cancer through the different signal ways. | Jian-Hua Tang He-Min Zhang Zhi-Hua Zhang Xiu-Long Zhang | 2017 | Asian Pacific Journal of Tropical Medicine2017，10，8： | 9 |
| 16 | Natural products:potential treatments for cisplatin-induced nephrotoxicity显示文摘Cisplatin is a clinically advanced and highly effective anticancer drug used in the treatment of a wide variety of malignancies,such as head and neck,lung,testis,ovary,breast cancer,etc.However,it has only a limited use in clinical practice due to its severe adverse effects,particularly nephrotoxicity;20%-35% of patients develop acute kidney injury(AKI)after cisplatin administration.The nephrotoxic effect of cisplatin is cumulative and dose dependent and often necessitates dose reduction or withdrawal.Recurrent episodes of AKI result in impaired renal tubular function and acute renal failure,chronic kidney disease,uremia,and hypertensive nephropathy.The pathophysiology of cisplatin-induced AKI involves proximal tubular injury,apoptosis,oxidative stress,inflammation,and vascular injury in the kidneys.At present,there are no effective drugs or methods for cisplatin-induced kidney injury.Recent in vitro and in vivo studies show that numerous natural products(flavonoids,saponins,alkaloids,polysaccharide,phenylpropanoids,etc.)have specific antioxidant,anti-inflammatory,and anti-apoptotic properties that regulate the pathways associated with cisplatin-induced kidney damage.In this review we describe the molecular mechanisms of cisplatin-induced nephrotoxicity and summarize recent findings in the field of natural products that undermine these mechanisms to protect against cisplatin-induced kidney damage and provide potential strategies for AKI treatment. | Chun-yan Fang Da-yong Lou Li-qin Zhou Jin-cheng Wang Bo Yang Qiao-jun He Jia-jia Wang Qin-jie Weng | 2021 | Acta Pharmacologica Sinica2021，42，12： | 9 |
| 17 | Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study显示文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials. | Shanshan Qin Hui Yu Xianghua Wu Zhiguo Luo Huijie Wang Si Sun Mingzhu Huang Jia Jin Zhonghua Tao Jie Qiao Yu Feng Jialei Wang Jianhua Chang | 2019 | Chinese Journal of Cancer Research2019，31，2： | 9 |
| 18 | Gene expression in cisplatin ototoxicity and protection with p53 inhibitor显示文摘Cisplatin damages cochlear hair cells and spiral ganglion neurons through cell death signaling pathways that are not fully understood. We used focused apoptosis gene microarrays to study early changes in gene expres- sion in cochlear cultures from P3 neonatal rats treated with cisplatin (0.2 mM). After 12 hours of cisplatin treat- ment, more than 50% of the 96 genes on the array showed a significant decrease in expression, consistent with widespread cell death. However, after 3 hours of cisplatin treatment, 10 genes showed significant increase in ex- pression in total cochlear tissue. In experiments with subsets of cochlear tissues, at 3h, cisplatin induced increased expression of 12 genes in the cochlear sensory epithelium (basilar membrane) and 11 genes in the spiral ganglion (tissue of Rosenthal's canal, containing the spiral ganglion). These included pro- and anti-apoptotic genes in- volved in the p53 signaling pathway, TNF receptor family, NF-kappaB pathway, death domain family, death effec- tor domain family, Bcl-2 family, CARD family, TRAF family, and GTP signal transduction. Although the changes in gene expression showed an overlap between basilar membrane and spiral ganglion, other changes, which may reflect the unique response of each tissue, were also observed. Pifithrin-α blocked cisplatin-induced up-regulation of genes in the p53 signaling pathway when assayed by both superarray and real time PCR. The data add to our understanding of the involvement of p53 in cisplatin-induced ototoxicity and otoprotection, conferred by the p53 inhibitor Pifithrin-α. | Donald Coling Richard Salvi | 2009 | Journal of Otology2009，4，2： | 9 |
| 19 | EZH2基因在人卵巢癌顺铂耐药株中的表达及其对细胞耐药性的影响显示文摘目的:检测果蝇zeste基因增强子同源物2(enhancer ofzestehomolog 2,EZH2)基因在人卵巢癌顺铂(cisplatin,DDP)耐药细胞株A2780/DDP及其亲本细胞株A2780中的表达差异,探讨以EZH2基因为靶向的RNA干扰能否有效逆转A2780/DDP细胞对DDP的耐药性。方法:采用实时荧光定量PCR(real-time fluorogenic quantitative PCR,RFQ-PCR)和Western印迹法检测EZH2 mRNA和蛋白在A2780/DDP及A2780细胞中的表达差异。人工构建4个靶向沉默EZH2基因的短发夹状RNA(short hairpin RNA,shRNA)质粒表达载体,脂质体法瞬时转染至A2780/DDP细胞,RFQ-PCR检测EZH2基因的沉默水平并挑选沉默效果最佳的质粒载体,G418加压筛选得到转染稳定的细胞株。RFQ-PCR和Western印迹法检测稳定转染后A2780/DDP细胞中EZH2基因的表达,MTT法检测转染细胞对DDP的耐药性。结果:A2780/DDP细胞中EZH2 mRNA和蛋白的表达量分别是A2780细胞表达量的(3.50±1.06)和(2.10±0.29)倍,差异有统计学意义(P<0.01)。稳定转染EZH2 shRNA后的A2780/DDP细胞,EZH2的mRNA及蛋白水平的表达量分别下降(83.66±5.65)%和(77.57±3.90)%(P<0.001),其对DDP的半数抑制浓度(half inhibitory concentration,IC50)值下降(61.33±11.40)%,差异有统计学意义(P<0.05)。结论:EZH2基因在A2780/DDP细胞中的表达明显升高,沉默EZH2基因能有效逆转A2780/DDP细胞对DDP的耐药性。 | 胡沙 王静 李智敏 郭剑锋 于利利 杨纯 王泽华 | 2010 | 肿瘤2010，30，9： | 9 |
| 20 | Concurrent chemoradiotherapy with weekly docetaxel versus cisplatin in the treatment of locoregionally advanced nasopharyngeal carcinoma:a propensity score-matched analysis显示文摘Background:Promising efficacy and manageable toxicity of docetaxel-based concurrent chemoradiotherapy(CCRT)were reported in head and neck cancer.In addition,the effect of CCRT in combination with cisplatin and/or 5-fluorouracil on both locoregionally advanced and metastatic/recurrent nasopharyngeal carcinoma(NPC)was verified.However,CCRT with docetaxel for locoregionally advanced NPC are not well studied.This study aimed to compare effectiveness and toxicities of CCRT with weekly docetaxel versus tri-weekly cisplatin for locoregionally advanced NPC.Methods:Clinical data of patients with locoregionally advanced NPC newly diagnosed between January 2010 and December 2014 receiving CCRT with either weekly docetaxel(15 mg/m2)or tri-weekly cisplatin(80-100 mg/m2)were reviewed.Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics.Adverse events and survival were compared between the two groups.Results:A total of 962 patients were included as the whole cohort,and 448 patients were matched and were regarded as the matched cohort.The median follow-up duration was 48 months for the whole cohort.The 3-year nodal recurrence-free survival rate was significantly increased for patients treated with docetaxel in both the whole(hazard ratio[HR]=0.37,95%confidence interval[CI]0.19-0.72,P=0.030)and matched cohorts(HR=0.33,95%CI 0.14-0.79,P=0.023).However,no significant differences were observed in overall survival,local recurrence-free survival,and distant metastasis-free survival between the two groups in both cohorts.Significantly higher rates of grade 3 radiodermatitis(6.7%vs.1.8%,P=0.001),mucositis(74.5%vs.37.9%,P<0.001),and leucopenia(2.2%vs.11.6%,P<0.001)were observed in the docetaxel group,but any grade of renal injury(1.8%vs.15.1%,P<0.001),vomiting(18.8%vs.88.3%,P<0.001),and ALT elevation(19.2%vs.31.3%,P=0.027)were more common in the cisplatin group.Conclusions:CCRT with weekly low-dose docetaxel is an effective and tolerable therapeutic regimen for locally advanced NPC.It provides a survival benefit mainly by improving the control of regional lymph node metastases,especially for patients with low pretreatment EBV DNA levels. | Jun-Fang Liao Qun Zhang Xiao-Jing Du Mei Lan Shan Liu Yun-Fei Xia Xiu-Yu Cai Wei Luo | 2019 | Cancer Communications2019，39，1： | 9 |
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