Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cis...Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.展开更多
The original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“...The original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“Yu-jun SHUAI”and“Chao HUANG”is“Department of Urology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China”,and both of them should be labeled as 1,as correctively appears on PDF.展开更多
Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the...Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear.To address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts.In these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was upregulated.Moreover,the expression of EMT-related transcription factors,including Slug,was elevated.On the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones.These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic changes.Moreover,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene transcription.These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.展开更多
The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the c...The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.展开更多
The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ...The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.展开更多
Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and...Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.展开更多
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...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.展开更多
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 advance...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.展开更多
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...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.展开更多
Objective: To study the influence of cisplatin implants on transplantation tumor growth and the expression of tissue kallikrein-7(KLK7) and E-cadherin(E-cad) in tumor-bearing mice with gastric cancer. Methods: BALB/c ...Objective: To study the influence of cisplatin implants on transplantation tumor growth and the expression of tissue kallikrein-7(KLK7) and E-cadherin(E-cad) in tumor-bearing mice with gastric cancer. Methods: BALB/c nude mice were collected as experimental animal and were randomly divided into model control group(Group A), tail intravenous injection of cisplatin group(Group B), intratumor injection of cisplatin group(Group C) and cisplatin implants treatment group(Group D). After the drugs intervening, the weight and volume of transplantation tumors were measured on Day 20, Day 30 and Day 40 and serum and KLK7 and E-cad contents in transplanted tumor tissue were examined. Results: On Day 20, Day 30 and Day 40 after treatment, the weight and volume of transplantation tumors of tumorbearing mice in four groups were different(Group A > Group B > Group C > Group D). The contents of KLK-7 and E-cad in tumor tissue and serum of tumor-bearing mice in four groups were different(Group A > Group B > Group C > Group D in KLK-7) and(Group A < Group B < Group C < Group D in E-cad). The weight and volume, and KLK7 and E-cad contents of transplantation tumors in four groups were significant difference(P<0.05). Conclusion: Cisplatin implants can inhibit the growth of transplanted tumor tissue and down-regulated KLK7 expression and up-regulated E-cad expression of tumor-bearing mice with gastric展开更多
INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo ...INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.展开更多
AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a ...AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage Ⅳ gastric cancer. In particular, 30 or 40 mg/m^2 of docetaxel on day 1, 60 mg/m^2 of cisplatin on day 1, and 2000 mg/m^2 of capecitabine for 2 wk were administered every three weeks.RESULTS Three patients were treated with modified DCX(m DCX) with 30 mg/m^2 docetaxel, and five patients were treated with this regimen with 40 mg/m^2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.CONCLUSION m DCX was well tolerated by Japanese patients with stage Ⅳ gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.展开更多
Objective:To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.Methods:We collected data from 18 patients undergoing cisplatin chemotherapy including serum electrolyte...Objective:To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.Methods:We collected data from 18 patients undergoing cisplatin chemotherapy including serum electrolytes,creatinine,blood urea nitrogen(BUN) and urine potassium,sodium and pH levels before and after the cisplatin chemotherapy.All the patients had cancer and were treated with 40-50 mg/day cisplatin.Renal injury was assessed by measuring serum electrolytes,creatinine,BUN levels and urine potassium,sodium and pH levels. Results:The five cycles of cisplatin based chemotherapy resulted in hypomagnesia(P=0.029), hypocalcaemia(P=0.001~*),hypophosphatemia(P=0.003*),hypokalemia(P=0.001~*)and increased serum creatinine(P=0.001~*)and BUN(P=0.292~*)levels.In urine analysis,decrease in potassium(P=0.024~*)was found,except potassium there was no significant changes in sodium and urine pH. Conclusions:The present study demonstrates that,acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances,when no corrective measures were initiated.展开更多
Objective: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-sm...Objective: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2–4 cycles of induction chemotherapy. Methods: Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy (60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction) was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy (CCRT). The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results: Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III (64 mg/m2) and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions: Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.展开更多
Purpose: To evaluate the feasibility of biweekly administration of cisplatin and vinorelbine as adjuvant chemotherapy for patients with completely resected non-small cell lung cancer (NSCLC). Patients and Methods: Thi...Purpose: To evaluate the feasibility of biweekly administration of cisplatin and vinorelbine as adjuvant chemotherapy for patients with completely resected non-small cell lung cancer (NSCLC). Patients and Methods: This was a single-arm, single-institutional study. Patients with completely resected NSCLC (p-Stage IB-IIIA) with no previous chemotherapy or radiotherapy were eligible. Simon’s optimal two-stage design was applied. Both cisplatin (50 mg/m2) and vinorelbine (25 mg/m2) were given on days 1 and 15, every 28 days. The primary endpoint of this study was the feasibility of this combination in the four cycles of treatment. Results: Twenty patients (19 lobectomies and 1 pneumonectomy) were enrolled in this study. 10 (50%) of patients had grade 3/4 neutropenia, and 3 (15%) had grade 3/4 anemia. Severe non-hematologic toxicities were uncommon in this series. No treatment-related death was encountered. 18 (90%) patients completed the planned 4 cycles of chemotherapy. The median intensity was 24.3 (range 18.1 to 25) mg/m2/week with an average of 23.6 (21 - 25) mg/m2/week cisplatin and 12.5 (range 10 to 12.5) mg/m2/week with an average of 12.3 (10 - 12.5) mg/m2/week vinorelbine. The median relative dose intensity of cisplatin was 97.5% (range 72.5% to 100%) with an average of 94.6% (72.5% - 100%) and that of vinorelbine was 100% (range 80% to 100%) with an average of 97.8% (80% - 100%). Conclusion: This regimen is feasible in the treatment of patients with completely resected NSCLC. A phase III trial is warranted to assess the efficacy of this regimen at promoting survival and preventing recurrence.展开更多
基金the Beijing Municipal Science and Technology Commission(grant Z211100002921013)the Tongzhou District Science and Technology Committee Project to Tongzhou(grant KJ2020CX010).
文摘Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.
文摘The original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“Yu-jun SHUAI”and“Chao HUANG”is“Department of Urology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China”,and both of them should be labeled as 1,as correctively appears on PDF.
基金the Japan Society for the Promotion of Science(JSPS),KAKENHI,Grant Number 26350974.
文摘Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear.To address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts.In these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was upregulated.Moreover,the expression of EMT-related transcription factors,including Slug,was elevated.On the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones.These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic changes.Moreover,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene transcription.These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.
基金supported by the National Natural Science Foundation of China(No.81703001)the Natural Science Foundation of Hebei Province(No.H2021406021),Hebei Province Medical Science Research Project(Nos.20210247,20221335)Hebei Province Government-Funded Clinical Medical Outstanding Talents Project,Chengde Medical University Scientific Research Major Projects(No.KY2020005).
文摘The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.
基金supported by Academic Leader Training Program of Pudong New Area Health System in Shanghai(Grant No.PWRd2021-13).
文摘The impact of different iron metabolism processes(DIMP)on ovarian cancer remains unclear.In this study,we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer.cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer.Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer.By analyzing 1669 serous ovarian cancer cases,we identified a range of mutations in iron metabolism genes,notably in those coding for the transferrin receptor(19%),melanotransferrin(19%),and ceruloplasmin(10%)in the iron import process,and glucose-6-phosphate isomerase(9%),hepcidin antimicrobial peptide(9%),metal regulatory transcription factor 1(8%),and bone morphogenetic protein 6(8%)in the iron regulation process.Compared to the unaltered group,the group with gene alterations exhibited a higher tumor mutation burden count(43 vs.54)and more advanced histologic grade(78.19%vs.87.90%).Compared to the normal ovarian counterparts,a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer;in contrast,an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer.Furthermore,in cisplatin-resistant cells compared to cisplatin-sensitive ones,the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased,while that of 8 out of the 10 genes in iron utilization was increased.In addition,survival curve analysis indicated that a higher expression in the majority of genes in the iron import process(12/21),or a reduced expression in most genes in the iron export process(4/5)correlated with poor progression-free survival.Additionally,TGF-βcould regulate the expression of most iron metabolism-associated genes;particularly,expression of genes involved in the iron storage process(2/2)was inhibited after TGF-β1 or TGF-β2 treatment.In conclusion,DIMP plays multifaceted roles in the initiation,chemo-resistance,and prognosis of ovarian cancer.Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer.
基金Supported by special program of molecular genetics medicine for women and children's health,National Center for Women and Children's Health.China Centers for Disease Control with Grant No.FY-ZX-ZD-0059
文摘Objective:To observe the anti-tumor effect of matrine combined with cisplatin on U14 rat models of cervical cancer.Methods:A total of 80 female Kunming rats were used to establish U14 rat models of cervical cancer and then divided into groups Ⅰ,Ⅱ,Ⅲ and Ⅳ,with 20 rats in each.For Group Ⅰ,the control group,injection of normal saline was given around the tumors.For Group Ⅱ,injection of 2 mg/kg cisplatin was given around the tumors.For Group Ⅲ,injection of 75 mg/kg matrine was given around the tumors while the combined injection of matrine and cisplatin was given for Group Ⅳ with the same doses as Groups Ⅱand Ⅲ.The animals were sacrificed 10 d after the injection and tumors were taken out for the comparisons of tumor weights after injection and calculation of anti-tumor rates,while thymus and spleen were taken for thymus index and spleen index.Blood in eyeball was collected for determination of changes in serum creatinine and urea nitrogen levels.Sections of tumor issue were prepared and morphological changes in tumor tissue cells were observed by using immunohistochemistry technique.Results:After injection,the thymus index and spleen index in Groups Ⅲ and Ⅳ were significantly higher than those in Groups Ⅰ and Ⅱ(P<0.05)while the two indexes in Group Ⅱ were significantly lower than Group Ⅰ(P<0.05).The tumor weights in Groups Ⅱ and Ⅳ were significantly smaller than those in Groups Ⅰ and Ⅲ(P<0.05) with significantly higher anti-tumor rates than Groups Ⅰ and Ⅲ(P<0.05).The serum creatinine and urea nitrogen levels in Groups Ⅲ and Ⅳ were significantly lower than Group Ⅱ(P<0.05) and the two indicators in Group Ⅲ were significantly lower than those in Group Ⅳ(P<0.05).The observation under the histological microscope showed densely arranged tumor cells in Group Ⅰ,growing as a crumby structure and diffuse appearance,with hyperchromatic and large nuclei,and abundant cytoplasm.In the case of Group Ⅱ,it showed less tumor cells,with extensive degenerative necrosis,sparse arrangement and karyopyknosis as well as karyoclasis.For Group Ⅲ,necrosis of tumor cells in different sizes and heterogeneous color in nuclei were observed.For Group Ⅳ,the number of tumor cells was significantly smaller than Groups Ⅰ and Ⅲ and the tumor cells presented an appearance of crumby structure as cancer nests,with more proliferation of connective tissue.Conclusions:The treatment of matrine combined with cisplatin can significantly improve the anti-tumor effect on U14 rats with cervical cancer,which can be a new option for the treatment for cervical cancer.
基金supported by the National "863" High‐Tech Res & Dev Program of China (No. 2006AA02A402)Beijing Municipal Science & Technology Commission Program "Optimization of pharmacotherapy and individual selection in gastric cancer" (No D101100050010023)
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.
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.
基金supported by Liaoning BaiQianWan Talents Program(No.2012921017)
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.
基金supported by Health Department of Hainan Province(Qiong 2013-self-financing 08)
文摘Objective: To study the influence of cisplatin implants on transplantation tumor growth and the expression of tissue kallikrein-7(KLK7) and E-cadherin(E-cad) in tumor-bearing mice with gastric cancer. Methods: BALB/c nude mice were collected as experimental animal and were randomly divided into model control group(Group A), tail intravenous injection of cisplatin group(Group B), intratumor injection of cisplatin group(Group C) and cisplatin implants treatment group(Group D). After the drugs intervening, the weight and volume of transplantation tumors were measured on Day 20, Day 30 and Day 40 and serum and KLK7 and E-cad contents in transplanted tumor tissue were examined. Results: On Day 20, Day 30 and Day 40 after treatment, the weight and volume of transplantation tumors of tumorbearing mice in four groups were different(Group A > Group B > Group C > Group D). The contents of KLK-7 and E-cad in tumor tissue and serum of tumor-bearing mice in four groups were different(Group A > Group B > Group C > Group D in KLK-7) and(Group A < Group B < Group C < Group D in E-cad). The weight and volume, and KLK7 and E-cad contents of transplantation tumors in four groups were significant difference(P<0.05). Conclusion: Cisplatin implants can inhibit the growth of transplanted tumor tissue and down-regulated KLK7 expression and up-regulated E-cad expression of tumor-bearing mice with gastric
基金Supported by the Youth Science Grant of Jiangshu Province,No.BQ98048.
文摘INTRODUCTIONThe main component of a traditional Chinese drug 'Pishuang'. arsenic trioxide (As2O3), has obviously selective anti-tumor effect on human hepatocellular carcinoma (HCC)in both in vitro and in vivo studies[1-5]. Due to limited effectiveness when any anti-carcinogen is used alone and obviously increased toxicity when the dose is raised, there is no exception for As2O3. Furthermore, combined chemotherapy contributes to improve therapeutic effectiveness, disperse toxicity and surmount drug-resistance,in which the combination of traditional Chinese and modern medicine has more advantages and characteristics. As a result,we made an experimental study on anti-tumor effect of As2O3in combination with cisplantin (PDD) or doxorubicin (ADM)on HCC. to investigate the possibility of AS2O3 in combination with PDD or ADM and nature of interaction between them,and to provide experimental basis for clinical application.
文摘AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients.METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage Ⅳ gastric cancer. In particular, 30 or 40 mg/m^2 of docetaxel on day 1, 60 mg/m^2 of cisplatin on day 1, and 2000 mg/m^2 of capecitabine for 2 wk were administered every three weeks.RESULTS Three patients were treated with modified DCX(m DCX) with 30 mg/m^2 docetaxel, and five patients were treated with this regimen with 40 mg/m^2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes.CONCLUSION m DCX was well tolerated by Japanese patients with stage Ⅳ gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.
文摘Objective:To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.Methods:We collected data from 18 patients undergoing cisplatin chemotherapy including serum electrolytes,creatinine,blood urea nitrogen(BUN) and urine potassium,sodium and pH levels before and after the cisplatin chemotherapy.All the patients had cancer and were treated with 40-50 mg/day cisplatin.Renal injury was assessed by measuring serum electrolytes,creatinine,BUN levels and urine potassium,sodium and pH levels. Results:The five cycles of cisplatin based chemotherapy resulted in hypomagnesia(P=0.029), hypocalcaemia(P=0.001~*),hypophosphatemia(P=0.003*),hypokalemia(P=0.001~*)and increased serum creatinine(P=0.001~*)and BUN(P=0.292~*)levels.In urine analysis,decrease in potassium(P=0.024~*)was found,except potassium there was no significant changes in sodium and urine pH. Conclusions:The present study demonstrates that,acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances,when no corrective measures were initiated.
基金support by the grant of the National Natural Science Foundation of China (No. 30870738)
文摘Objective: To evaluate the maximum tolerated dose (MTD) of docetaxel (DCT) and cisplatin (DDP) concurrently with three dimensional (3D) conformal radiotherapy or IMRT for patients with locally advanced non-small cell lung cancer (stage IIIa and IIIb) after 2–4 cycles of induction chemotherapy. Methods: Fourteen patients with histological/cytological proven stage III non–small-cell lung cancer were eligible. 3D or IMRT radiotherapy (60-70Gy in 30-35 fractions, 6-7weeks, 2 Gy/fraction) was delivered concurrently with cisplatin and docetaxel, 2 cycles during concurrent chemoradiotherapy (CCRT). The level I dosage was composed of 56 mg/m2 DCT, on day 1 and 28mg/m2 DDP, on day 1 and day 2. The level II was composed of 60 mg/m2 DCT, on day 1 and 30 mg/ m2 DDP, on day 1 and day 2. The level III was composed of 64 mg/m2 DCT, on day 1 and 32 mg/ m2 DDP, on day 1 and day 2. Results: Fourteen patients were allocated and finished concurrent chemoradiotherapy. The dose-limiting neutropenia was at the dose Level III (64 mg/m2) and occurred in 2 of 5 patients. No dose limiting non-hematologic or hematologic toxicity occurred in the other patients. Conclusions: Patients with locally advanced non-small cell lung cancer may tolerate 60mg/m2 docetaxel and 60mg/m2 cisplatin for 2 cycles during concurrent radiotherapy after 2-3 cycles of induction chemotherapy.
文摘Purpose: To evaluate the feasibility of biweekly administration of cisplatin and vinorelbine as adjuvant chemotherapy for patients with completely resected non-small cell lung cancer (NSCLC). Patients and Methods: This was a single-arm, single-institutional study. Patients with completely resected NSCLC (p-Stage IB-IIIA) with no previous chemotherapy or radiotherapy were eligible. Simon’s optimal two-stage design was applied. Both cisplatin (50 mg/m2) and vinorelbine (25 mg/m2) were given on days 1 and 15, every 28 days. The primary endpoint of this study was the feasibility of this combination in the four cycles of treatment. Results: Twenty patients (19 lobectomies and 1 pneumonectomy) were enrolled in this study. 10 (50%) of patients had grade 3/4 neutropenia, and 3 (15%) had grade 3/4 anemia. Severe non-hematologic toxicities were uncommon in this series. No treatment-related death was encountered. 18 (90%) patients completed the planned 4 cycles of chemotherapy. The median intensity was 24.3 (range 18.1 to 25) mg/m2/week with an average of 23.6 (21 - 25) mg/m2/week cisplatin and 12.5 (range 10 to 12.5) mg/m2/week with an average of 12.3 (10 - 12.5) mg/m2/week vinorelbine. The median relative dose intensity of cisplatin was 97.5% (range 72.5% to 100%) with an average of 94.6% (72.5% - 100%) and that of vinorelbine was 100% (range 80% to 100%) with an average of 97.8% (80% - 100%). Conclusion: This regimen is feasible in the treatment of patients with completely resected NSCLC. A phase III trial is warranted to assess the efficacy of this regimen at promoting survival and preventing recurrence.