Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 817
Filter
1.
Electron. j. biotechnol ; 50: 10-15, Mar. 2021. ilus, graf, tab
Article in English | LILACS | ID: biblio-1292308

ABSTRACT

BACKGROUND: LXYL-P1-2 is the first reported glycoside hydrolase that can catalyze the transformation of 7-b-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT) by removing the D-xylosyl group at the C7 position. Successful synthesis of paclitaxel by one-pot method combining the LXYL-P1-2 and 10- deacetylbaccatin III-10-b-O-acetyltransferase (DBAT) using XDT as a precursor, making LXYL-P1-2 a highly promising enzyme for the industrial production of paclitaxel. The aim of this study was to investigate the catalytic potential of LXYL-P1-2 stabilized on magnetic nanoparticles, the surface of which was modified by Ni2+-immobilized cross-linked Fe3O4@Histidine. RESULTS: The diameter of matrix was 20­40 nm. The Km value of the immobilized LXYL-P1-2 catalyzing XDT (0.145 mM) was lower than that of the free enzyme (0.452 mM), and the kcat/Km value of immobilized enzyme (12.952 mM s 1 ) was higher than the free form (8.622 mM s 1 ). The immobilized form maintained 50% of its original activity after 15 cycles of reuse. In addition, the stability of immobilized LXYL-P1-2, maintained 84.67% of its initial activity, improved in comparison with free form after 30 d storage at 4 C. CONCLUSIONS: This investigation not only provides an effective procedure for biocatalytic production of DT, but also gives an insight into the application of magnetic material immobilization technology.


Subject(s)
Paclitaxel/biosynthesis , Glycoside Hydrolases/metabolism , Kinetics , Enzymes, Immobilized , Nanoparticles , Magnets
2.
Article in Chinese | WPRIM | ID: wpr-880142

ABSTRACT

OBJECTIVE@#To analyze gene expression profile of T cell lymphoma Jurkat cell line treated with paclitaxel by computational biology based on next generation sequencing and to explore the possible molecular mechanism of paclitaxel resistance to T cell lymphoma at gene level.@*METHODS@#IC50 of paclitaxel on Jurkat cell line was determined by CCK-8 assay. Gene expression profile of Jurkat cells treated with paclitaxel was acquired by next generation sequencing technology. Gene microarray data related to human T cell lymphoma were screened from Gene Expression Omnibus (GEO) database (including 720 cases of T cell lymphoma and 153 cases of normal tissues). Combined with the sequencing data, differential expression genes (DEGs) were intersected and screened. DAVID database was used for enrichment analysis of GO function and KEGG pathway to determine and visualize functional entries of DEGs, and protein-protein interactions network of DEGs was drawn. The levels of gene expression were detected and verified by RT-qPCR.@*RESULTS@#CCK-8 results showed that the proliferation of Jurkat cells was inhibited by paclitaxel depended on the concentration apparently. Treated by paclitaxel for 48 h, P<0.05 and |log2(FC)|≥1 were used as filter criteria on the results of RNA Sequencing (RNA-Seq) and GeoChip, 351 DEGs were found from Jurkat cells, including 323 up-regulated genes and 28 down-regulated genes. The GO functional annotation and KEGG pathway enrichment analysis showed that the role of paclitaxel was mainly concentrated in protein heterodimerization activity, nucleosome assembly and transcriptional dysregulation in cancer, etc. The results of RT-qPCR were consistent with those of the sequencing analysis, which verified the reliability of this sequencing.@*CONCLUSION@#Paclitaxel can affect the proliferation and apoptosis of T-cell lymphoma by up-regulating JUN gene, orphan nuclear receptor NR4A family genes and histone family genes.


Subject(s)
Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , High-Throughput Nucleotide Sequencing , Humans , Lymphoma, T-Cell , Paclitaxel , Reproducibility of Results
3.
Article in Chinese | WPRIM | ID: wpr-879151

ABSTRACT

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 μg·mL~(-1) and 0.66 μg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Drug Carriers , Female , Folic Acid , Glycolates , HeLa Cells , Humans , Micelles , Paclitaxel , Particle Size , Uterine Cervical Neoplasms/drug therapy
4.
Braz. j. med. biol. res ; 53(6): e8885, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132519

ABSTRACT

In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.


Subject(s)
Animals , Male , Female , Rabbits , Ovarian Neoplasms/drug therapy , Sesquiterpenes/administration & dosage , Cell Movement/drug effects , NF-kappa B/adverse effects , Paclitaxel/administration & dosage , Apoptosis/drug effects , Cell Proliferation/drug effects , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Immunohistochemistry , Transfection , Signal Transduction , Blotting, Western , NF-kappa B/metabolism , Cell Line, Tumor , Real-Time Polymerase Chain Reaction , Mice, Inbred BALB C
5.
Article in English | WPRIM | ID: wpr-881034

ABSTRACT

Paclitaxel, a tetracyclic diterpenoid compounds, was firstly isolated from the bark of the Pacific yew trees. Currently, as a low toxicity, high efficiency, and broad-spectrum natural anti-cancer drug, paclitaxel has been widely used against ovarian cancer, breast cancer, uterine cancer, and other cancers. As the matter of fact, natural paclitaxel from Taxus species has been proved to be environmentally unsustainable and economically unfeasible. For this reason, researchers from all over the world are devoted to searching for new ways of obtaining paclitaxel. At present, other methods, including artificial cultivation of Taxus plants, microbial fermentation, chemical synthesis, tissue and cell culture have been sought and developed subsequently. Meanwhile, the biosynthesis of paclitaxel is also an extremely attractive method. Unlike other anti-cancer drugs, paclitaxel has its unique anti-cancer mechanisms. Here, the source, production, and anti-cancer mechanisms of paclitaxel were summarized and reviewed, which can provide theoretical basis and reference for further research on the production, anti-cancer mechanisms and utilization of paclitaxel.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Humans , Neoplasms/drug therapy , Paclitaxel/pharmacology
6.
Article in English | WPRIM | ID: wpr-811217

ABSTRACT

OBJECTIVE: To evaluate the effectiveness and safety of the combination of pegylated liposomal doxorubicin with carboplatin (CD) compared with those of carboplatin and paclitaxel (CP) for platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer in a real-world setting in Korea.METHODS: We enrolled relevant patients from 9 institutions. All patients received CD or CP as the second- or third-line chemotherapy in routine clinical practice during 2013–2018. The primary endpoints were progression-free survival (PFS) and toxicity. The secondary endpoint included the objective response rate (ORR).RESULTS: Overall, 432 patients (224 and 208 in the CD and CP groups, respectively) were included. With a median follow-up of 18.9 months, the median PFS was not different between the groups (12.7 vs. 13.6 months; hazard ratio, 1.161; 95% confidence interval, 0.923–1.460; p=0.202). The ORR was 74.6% and 80.1% in the CD and CP group, respectively (p=0.556). Age and surgery at relapse were independent prognostic factors. More patients in the CD group significantly experienced a grade 3 to 4 hematologic toxicity and hand-foot syndrome (13.8% vs. 6.3%), whereas grade 2 or more alopecia (6.2% vs. 36.1%), peripheral neuropathy (4.4% vs. 11.4%), and allergic/hypersensitivity reaction (0.4% vs. 8.5%) developed more often in the CP group.CONCLUSIONS: The safety and effectiveness of chemotherapy with CD in a real-world setting were consistent with the results from a randomized controlled study. The different toxicity profiles between the 2 chemotherapy (CD and CP) regimens should be considered in the clinical practice.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03562533


Subject(s)
Alopecia , Carboplatin , Cohort Studies , Disease-Free Survival , Doxorubicin , Drug Therapy , Follow-Up Studies , Hand-Foot Syndrome , Humans , Korea , Ovarian Neoplasms , Paclitaxel , Peripheral Nervous System Diseases , Platinum , Prognosis , Recurrence , Retrospective Studies
7.
Article in English | WPRIM | ID: wpr-811212

ABSTRACT

OBJECTIVE: To compare the efficacy and toxicity of dose-dense weekly paclitaxel and 3-weekly carboplatin (ddPC) as neoadjuvant chemotherapy (NAC) with the standard 3-weekly regimen.METHODS: A retrospective study of patients diagnosed with stage IIIc and IV ovarian cancer who received at least one cycle of NAC followed by interval debulking surgery between August 2015 and January 2018 was conducted. Patient characteristics, clinical and pathological response to NAC, surgical and survival outcome, and adverse event were compared.RESULTS: A total of 23 patients in the ddPC group and 50 patients in the standard group received a median of 3 cycles of NAC. Rate of grade ≥3 neutropenia was significantly higher in the ddPC group than the standard (82.6% vs. 22.0%, p<0.001). Patients in the ddPC group underwent dose-reduction more frequently (34.8% vs. 4.00%, p=0.001). Normalization of cancer antigen-125 post-NAC occurred more frequently in the ddPC group (73.9% vs. 46.0%, p=0.030). No residual disease rate (43.5% vs. 60.0%, p=0.188) and chemotherapy response score of 3 (34.8% vs. 26.0%, p=0.441) were not statistically different between two groups. There was no statistical difference in progression free survival (PFS) at 2 years (36.3% vs. 28.4%, p=0.454). Cox proportional hazard model showed that ddPC was not a significant determinant of PFS (p=0.816).CONCLUSION: There was no difference between both regimens in terms of NAC response and survival outcomes. However, ddPC group showed higher hematologic toxicity requiring dose reduction.


Subject(s)
Carboplatin , Disease-Free Survival , Drug Therapy , Humans , Neoadjuvant Therapy , Neutropenia , Ovarian Neoplasms , Paclitaxel , Proportional Hazards Models , Retrospective Studies , Treatment Outcome
8.
Article in Chinese | WPRIM | ID: wpr-828855

ABSTRACT

OBJECTIVE@#To investigate the role of long-chain non-coding RNA MALAT1 in modulating paclitaxel resistance in breast cancer cells.@*METHODS@#Breast cancer SK-BR-3 cells were treated with gradient concentrations of paclitaxel to induce paclitaxel resistance of the cells. The resistant cells were transfected with si-NC, si-MALAT1, pcDNA, pcDNA-MALAT1, miRNC, miR-485-3p mimics, si-MALAT1+anti-miR-NC, or si-MALAT1+anti-miR-485-3p liposomes. Following the transfections, the cells were examined for changes in IC of paclitaxel using MTT assay; the protein expression of P-gp, Bcl-2 and Bax were detected with Western blotting, and a dual luciferase reporter assay was used to detect the binding of MALAT1 to miR-485-3p.@*RESULTS@#Compared with paclitaxel-sensitive SK-BR-3 cells, paclitaxel-resistant SK-BR-3 cells showed significantly increased the IC of paclitaxel with up-regulated MALAT1 expression and down-regulated miR-485-3p expression ( < 0.05). Silencing MALAT1 or overexpressing miR-485-3p obviously lowered the IC of paclitaxel and the expression of P-gp and Bcl-2 and increased the expression of Bax in SK-BR-3/PR cells ( < 0.05). miR-485-3p was identified as the target of MALAT1, and inhibiting miR-485-3p significantly reverse the effect of MALAT1 silencing on IC of paclitaxel and the expressions of P-gp, Bcl-2 and Bax in SK-BR-3/PR cells ( < 0.05).@*CONCLUSIONS@#MALAT1 can modulate paclitaxel resistance in breast cancer cells possibly by targeting miR-485-3p to down-regulate P-gp and Bcl-2 and up-regulate Bax.


Subject(s)
Cell Line, Tumor , Humans , MicroRNAs , Paclitaxel , RNA, Long Noncoding , Genetics
9.
Article in Chinese | WPRIM | ID: wpr-828535

ABSTRACT

Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.


Subject(s)
Antineoplastic Agents , Doxorubicin , Drug Delivery Systems , Gene Transfer Techniques , Humans , Mesenchymal Stem Cells , Neoplasms , Therapeutics , Paclitaxel , Research
10.
Article in Chinese | WPRIM | ID: wpr-828049

ABSTRACT

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.


Subject(s)
Animals , Breast Neoplasms , Cell Line, Tumor , Ganoderma , Mice , Neoplasms , Paclitaxel , Poloxamer , Polysaccharides
11.
Article in English | WPRIM | ID: wpr-787536

ABSTRACT

BACKGROUND/OBJECTIVES: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%. The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways.MATERIALS #SPCHAR_X0026; METHODS: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo.RESULTS: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts.CONCLUSION: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.


Subject(s)
Blotting, Western , Caspase 3 , Cell Cycle , Cell Death , Cell Line , Cell Survival , Diagnosis , DNA Fragmentation , Flow Cytometry , Heterografts , Humans , In Vitro Techniques , Paclitaxel , Protein-Tyrosine Kinases , Survival Rate , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Tumor Burden
12.
Article in Chinese | WPRIM | ID: wpr-772069

ABSTRACT

OBJECTIVE@#To investigate the effects of ribonucleotide reductase catalytic subunit M1 (RRM1) gene silencing on drug resistance of human breast cancer cell line MCF-7/R.@*METHODS@#We established a paclitaxel-resistant breast cancer MCF-7 cell line (MCF-7/R) by exposing the cells to high-concentration paclitaxel in a short time. Small interfering RNAs (siRNAs) targeting RRM1 were designed to silence RRM1 expression in human breast cancer MCF-7/R cells. MTT assay was used to detect the IC values and the sensitivity to paclitaxel in the cells with or without siRNA transfection. The changes in the proliferative activity of MCF7 and MCF-7/R cells following RRM1 gene silencing were evaluated using EdU assay. Flow cytometry was used to analyze the cell apoptosis and cell cycle changes. We assessed the effect of RRM1 gene silencing and paclitaxel on the tumor growth in a nude mouse model bearing subcutaneous xenografts with or without siRNA transfection.@*RESULTS@#We detected significantly higher expressions of RRM1 at both the mRNA and protein levels in the drug-resistant MCF- 7/R cells than in the parental MCF-7 cells ( < 0.01). Transfection with the specific siRNAs significantly reduced the expression of RRM1 in MCF-7/R cells ( < 0.05), which showed a significantly lower IC value of paclitaxel than the cells transfected with the negative control siRNA ( < 0.05). RRM1 silencing significantly inhibited the proliferation ( < 0.01) and enhanced the apoptosis-inducing effect of paclitaxel in MCF-7/R cells ( < 0.001); RRM1 silencing also resulted in obviously reduced Akt phosphorylation, suppressed Bcl-2 expression and promoted the expression of p53 protein in MCF-7/R cells. In the tumor-bearing nude mice, the volume of subcutaneously transplanted tumors was significantly smaller in MCF-7/R/siRNA+ PTX group than in the other groups ( < 0.001).@*CONCLUSIONS@#RRM1 gene silencing can reverse paclitaxel resistance in human breast cancer cell line MCF-7/R by promoting cell apoptosis.


Subject(s)
Animals , Apoptosis , Breast Neoplasms , Drug Resistance, Neoplasm , Gene Silencing , Humans , MCF-7 Cells , Mice , Mice, Nude , Paclitaxel , RNA, Small Interfering , Ribonucleotide Reductases , Tumor Suppressor Proteins
13.
Chinese Journal of Biotechnology ; (12): 1109-1116, 2019.
Article in Chinese | WPRIM | ID: wpr-771817

ABSTRACT

The discovery of hydroxylases in the anticancer drug taxol biosynthesis pathway is a hotspot and difficulty in current research. In this study, a new hydroxylase gene TcCYP725A22 (GenBank accession number: MF448646.1) was used to construct a sub-cellular localization vector pCAMIBA1303-TcCYP725A22-EGFP to get the transient expression in onion epidermal cells. Laser confocal microscopy revealed that the protein encoded by this gene was localized in the cell membrane. Furthermore, the recombinant plant expression plasmid pBI121-TcCYP725A22 was constructed. After transient transformation to the Taxus chinensis mediated by Agrobacterium tumefaciens LBA4404, qRT-PCR and LC-MS were utilized to analyze the effects of TcCYP725A22 overexpression on the synthesis of taxol. The results showed that, in the TcCYP725A22 overexpressed cell line, expression levels of most defined hydroxylase genes for taxol biosynthesis were increased, and the yield of taxanes were also increased. It was concluded that the hydroxylase gene TcCYP725A22 is likely involved in the biosynthetic pathway of taxol.


Subject(s)
Biosynthetic Pathways , Mixed Function Oxygenases , Paclitaxel , Taxoids , Taxus
14.
Article in Chinese | WPRIM | ID: wpr-773126

ABSTRACT

Paclitaxel( PTX) is used as a broad spectrum anti-tumor medicine. However,serious drawbacks restrict clinical application of PTX. In this study,we prepared tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier containing paclitaxel( BSALC/DOPE-PTX) to study the effective antitumor activity. The in vivo targeting ability of the nanocarrier in tumor bearing nude mice was evaluated by using a Kodak in vivo imaging system FX PRO. The in vivo anti-tumor activity was evaluated in MDA-MB-231 tumor bearing mice,and representative sections were stained with hematoxylin and eosin( H&E),and examined by light microscopy. The results showed that DiR-loaded FA-BSA-LC/DOPE selectively targeted tumor,and had a relatively long residence in the tumor tissue. According to the in vivo anti-tumor activity study,FA-BSA-LC/DOPE-PTX exhibited an outstanding tumor inhibition effect with a tumor growth inhibition rate of 79.3%,and tumor tissue sections stained by hematoxylin and eosin( HE) showed severe necrosis areas and many dead cells with condensed nuclei in the FA-BSA-LC/DOPE-PTX group. Therefore,FA-BSA-LC/DOPE-PTX is a biocompatible,tumor-targeting and pH-sensitive lipoprotein-mimic nanocarrier,with a very marked anti-tumor activity in tumor-bearing mice in vivo.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Pharmacology , Cell Line, Tumor , Drug Carriers , Hydrogen-Ion Concentration , Lipoproteins , Mice , Mice, Nude , Nanoparticles , Neoplasms, Experimental , Drug Therapy , Paclitaxel , Pharmacology
15.
Article in English | WPRIM | ID: wpr-719307

ABSTRACT

OBJECTIVES: We conducted a protocol-based cohort study to evaluate the outcomes of interval debulking surgery (IDS) followed by paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of advanced-stage ovarian cancer. METHODS: From October 2015 to May 2018, 65 patients with stages IIIC–IV ovarian cancer were treated according to the study protocol. HIPEC was performed with paclitaxel (175 mg/m2) for 90 minutes, only in cases of optimal cytoreduction. RESULTS: Of 65 patients, 40 (61.5%) patients underwent neoadjuvant chemotherapy (NAC), 34 (52.3%) patients had a high tumor burden with a Fagotti score ≥8 at diagnostic laparoscopy, and 6 (9.2%) had definite stage IV metastasis and/or poor performance status before NAC. Twenty-seven (41.5%) patients underwent IDS followed by HIPEC. The mean duration of IDS with HIPEC was 543.8 (range, 277.0–915.0) minutes. Grade III/IV perioperative complications occurred in 7.4% (n=2)/3.7% (n=1) of patients and no cases of mortality were reported within 30 days postoperatively. The median progression-free survival was 21.3 months, and the median overall survival was not reached for those who received HIPEC. CONCLUSIONS: According to our study protocol, IDS followed by paclitaxel-based HIPEC as a first-line treatment appears to be feasible and safe for the treatment of advanced-stage ovarian cancer. Further evaluations of this procedure are required to assess its survival benefits.


Subject(s)
Cohort Studies , Disease-Free Survival , Drug Therapy , Humans , Laparoscopy , Mortality , Neoplasm Metastasis , Ovarian Neoplasms , Paclitaxel , Pilot Projects , Tumor Burden
16.
Article in English | WPRIM | ID: wpr-760645

ABSTRACT

The long-term survival of heavily pretreated patients with primary peritoneal cancer (PPC) is uncommon. Here, we report on a patient with PPC refractory to multiple lines of intravenous chemotherapy, namely, a combined regimen of paclitaxel and carboplatin, and single regimens of topotecan, docetaxel, cisplatin, and gemcitabine. However, after intraperitoneal (IP) chemotherapy with paclitaxel-cisplatin, the patient's condition improved, and she has been progression-free for more than 4 years. Interestingly, before the IP chemotherapy, the recurrences were limited to the peritoneal cavity. These results suggest that IP recurrence might be a predictor of a good response to IP chemotherapy.


Subject(s)
Carboplatin , Cisplatin , Drug Therapy , Humans , Infusions, Parenteral , Neoplasm Recurrence, Local , Ovarian Neoplasms , Paclitaxel , Peritoneal Cavity , Peritoneal Neoplasms , Recurrence , Topotecan
17.
Article in Korean | WPRIM | ID: wpr-759767

ABSTRACT

Nivolumab is anti-programmed death 1 (PD1) receptor antibody, which can be used in the treatment of metastatic squamous cell cancer. By blocking the PD1 receptors on T cells, it enhances T-cell response against cancer cells. A 69-year-old man, who works as a farmer, presented with erythematous lichenified plaques on sun-exposed areas, such as the face, the chest, and both the forearms. Before the hospital visit, he was receiving lung cancer treatment with paclitaxel and cisplatin, but there was no improvement. Subsequently, the regimen was changed into nivolumab, and PET-CT showed decreased in cancer size. However, skin rashes developed simultaneously. It is consistent with the results of a previous study in which cutaneous side effects developed in 42% of responders compared to 7% of non-responders. Herein, we report a case of nivolumab-induced cutaneous toxicity on sun-exposed areas based on the clinical findings, including the distribution of rashes, which were improved after decreasing the nivolumab dose with literature review.


Subject(s)
Aged , Cisplatin , Exanthema , Farmers , Forearm , Humans , Lung Neoplasms , Neoplasms, Squamous Cell , Paclitaxel , Programmed Cell Death 1 Receptor , T-Lymphocytes , Thorax
18.
Gut and Liver ; : 471-478, 2019.
Article in English | WPRIM | ID: wpr-763852

ABSTRACT

BACKGROUND/AIMS: Metallic stents designed to relieve malignant biliary obstruction are susceptible to occlusive tumor ingrowth or overgrowth. In a previous report, we described metallic stents covered with paclitaxel-incorporated membrane (MSCPM-I, II) to prevent occlusion from tumor ingrowth via antitumor effect. This new generation paclitaxel-eluting biliary stent is further endowed with sodium caprate (MSCPM-III) for enhanced drug delivery. The purpose of this study is to examine the safety of its drug delivery system in the porcine biliary tract. METHODS: MSCPM-III (10% [wt/vol] paclitaxel) and covered metal stents (CMSs) were endoscopically inserted in porcine bile ducts in vivo. Histologic biliary changes, levels of paclitaxel released, and various serum analytes (albumin, alkaline phosphate, aspartate transaminase, alanine transaminase, total protein, total bilirubin, and direct bilirubin) were assessed. RESULTS: Based on the intensity of reactive inflammation and fibrosis, changes in porcine biliary epithelium secondary to implanted MSCPM-III were deemed acceptable (i.e., safe). Histologic features in the MSCPM-III and CMS groups did not differ significantly. In a related serum analysis, paclitaxel release from MSCPM-III stents was below the limit of detection for 28 days. Biochemical analyses were also similar for the two groups, and no evidence of hepatic or renal toxicity was found in animals receiving MSCPM-III stents. CONCLUSIONS: In a prototypic porcine trial, this newly devised metal biliary stent incorporating both paclitaxel and sodium caprate appears to be safe in the porcine bile duct.


Subject(s)
Alanine Transaminase , Animals , Aspartate Aminotransferases , Bile Ducts , Biliary Tract Neoplasms , Biliary Tract , Bilirubin , Drug Delivery Systems , Drug-Eluting Stents , Epithelium , Fibrosis , Inflammation , Limit of Detection , Membranes , Paclitaxel , Pancreatic Neoplasms , Self Expandable Metallic Stents , Sodium , Stents
19.
Cancer Research and Treatment ; : 1117-1127, 2019.
Article in English | WPRIM | ID: wpr-763168

ABSTRACT

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.


Subject(s)
Animals , Carboplatin , Cause of Death , Drug Therapy , Exome , Female , Gene Expression , Genome , Heterografts , Humans , Mice , Odds Ratio , Ovarian Neoplasms , Ovary , Paclitaxel , Recurrence , Sequence Analysis, RNA , Statistics as Topic
20.
Article in English | WPRIM | ID: wpr-763128

ABSTRACT

PURPOSE: This study was conducted to develop and validate an individualized prediction model for automated detection of acquired taxane resistance (ATR). MATERIALS AND METHODS: Penalized regression, combinedwith an individualized pathway score algorithm,was applied to construct a predictive model using publically available genomic cohorts of ATR and intrinsic taxane resistance (ITR). To develop a model with enhanced generalizability, we merged multiple ATR studies then updated the learning parameter via robust cross-study validation. RESULTS: For internal cross-study validation, the ATR model produced a perfect performance with an overall area under the receiver operating curve (AUROC) of 1.000 with an area under the precision-recall curve (AUPRC) of 1.000, a Brier score of 0.007, a sensitivity and a specificity of 100%. The model showed an excellent performance on two independent blind ATR cohorts (overall AUROC of 0.940, AUPRC of 0.940, a Brier score of 0.127). When we applied our algorithm to two large-scale pharmacogenomic resources for ITR, the Cancer Genome Project (CGP) and the Cancer Cell Line Encyclopedia (CCLE), an overall ITR cross-study AUROC was 0.70, which is a far better accuracy than an almost random level reported by previous studies. Furthermore, this model had a high transferability on blind ATR cohorts with an AUROC of 0.69, suggesting that general predictive features may be at work across both ITR and ATR. CONCLUSION: We successfully constructed a multi-study–derived personalized prediction model for ATR with excellent accuracy, generalizability, and transferability.


Subject(s)
Cell Line , Cohort Studies , Drug Resistance , Genome , Humans , Learning , Machine Learning , Methods , Paclitaxel , Sensitivity and Specificity , Taxoids
SELECTION OF CITATIONS
SEARCH DETAIL