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.
Biosynthetic Pathways ; Mixed Function Oxygenases ; Paclitaxel ; Taxoids ; Taxus

PURPOSE: Breast cancer is heterogeneous disease and the response to chemotherapeutic agents is also heterogeneous from patient to patient. Chemotherapy response assay is in vitro test that is performed to evaluate the degree of tumor growth inhibition by chemotherapy drugs. In this study, we performed the chemotherapy response assay using adenosine triphosphate (ATP-CRA) in breast cancer patients and assessed the clinical availability. METHODS: Sixty five breast cancer patients were enrolled in this study. Cancer cells were evenly divided and treated with commonly used chemotherapeutic drugs in breast cancer (doxorubicin, epirubicin, 5-fluorouracil, paclitaxel, docetaxel, vinorelbine, and gemcitabine). To verify in vitro ATP-CRA indirectly, we analyzed the correlation between cell death rate (CDR) of doxorubicin and epirubicin, and between doxorubicin and paclitaxel. We also analyzed the mean CDR of doxorubicin, epirubicin and paclitaxel by HER2 status. RESULTS: We could successfully perform the ATP-CRA in 60 patients (95.2%). In all cases, we can get the results within 7 days. The range of CDR was very wide, from 0 to more than 50%, except gemcitabine. Epirubicin showed the highest mean CDR (39.9%) and doxorubicin, paclitaxel in order. According to the chemosensitivity index, paclitaxel is the most frequently first-ranked and doxorubicin, epirubicin in order. Correlation coefficient between the cell death rate of doxorubicin and epirubicin is 0.4210 and 0.1299 between paclitaxel and doxorubicin. In HER2 positive group, mean CDR of paclitaxel, epirubicin and doxorubicin was higher than in HER2 negative group, even though epirubicin and doxorubicin were not statistically significant (p=0.018, p=0.114, p=0.311, respectively). CONCLUSION: ATP-CRA showed heterogeneous results in individual patients. ATP-CRA was successful and can be performed within short time period. According to our in vitro study, it showed similar results with in vivo study but for the clinical use, the prospective randomized controlled trial should be preceded.
Adenosine Triphosphate ; Breast ; Breast Neoplasms ; Cell Death ; Deoxycytidine ; Doxorubicin ; Epirubicin ; Fluorouracil ; Humans ; Paclitaxel ; Polyphosphates ; Taxoids ; Vinblastine

Adjuvant chemotherapy plays an important role in improving disease free and overall survival in women with high-risk early stage breast cancer. While more than seventy thousand women have enrolled in taxane-based adjuvant chemotherapy studies, interim and final results are available from several of these randomized phase III adjuvant studies. In this review, we will summarize the design and outcomes from the reported trials, and draw conclusions about the role adjuvant taxanes now play in the standard management of operable breast cancer. In aggregate, these studies show that adjuvant taxanes can improve important clinical outcomes beyond those achieved with anthracycline-based chemotherapy, without imparting prohibitive acute or chronic toxicities. Important questions are being addressed in ongoing adjuvant trials, including comparisons of combination to sequential therapy, direct comparisons between paclitaxel and docetaxel, and how to safely integrate targeted therapies into these highly active adjuvant regimens.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Drug Therapy ; Female ; Humans ; Paclitaxel ; Taxoids*

Paclitaxel is one of the taxoid-antineoplastic agents. These agents are used in the treatment of breast, lung and ovary cancer. Nail changes due to treatment with the taxanes (mainly docetaxel) are reported in 30~40 percent of patients. Paclitaxel is not commonly associated with dermatological reactions, although localized skin reactions and tissue necrosis following extravasation have been reported. Reports of the incidence of nail changes associated with paclitaxel is noted as the pigmentation or discoloration of the nail bed, vary from 2~20%. We report a patient with onycholysis and subungual suppuration during treatment with paclitaxel.
Breast ; Humans ; Incidence ; Lung ; Nails ; Necrosis ; Onycholysis ; Ovarian Neoplasms ; Paclitaxel ; Pigmentation ; Skin ; Suppuration ; Taxoids

Anaplastic thyroid carcinoma (ATC) is a rare type of malignancy of thyroid follicular cell origin. It is one of the most aggressive human cancers, and typically associated with a fatal prognosis. Most patients are presenting as locally advanced and systemically disseminated disease. A single mode of therapy, whether it is surgery, chemotherapy, or radiotherapy, fails to afford significantly favorable outcomes. While multimodality approaches may enhance the treatment response to a small degree, such implementations of these modalities are often impractical as many patients are of old age and are unable to tolerate the intensity of treatments. As in many other types of carcinomas, radical resection may be the mainstay of therapy for ATC, but surgery itself is seldom possible for this condition. Even with aggressive surgical therapy for those invasive ATCs, there is no evidence of decreased recurrence rates, while only the post-surgical morbidity rates increase. One chemotherapeutic agent that seems to demonstrate some effect against ATC is adriamycin, which is more effective when administered in combination, and is also known to act synergistically with radiotherapy. A commonly employed treatment modality is the combination therapy of adriamycin and cisplatin administration with hyperfractionated radiation therapy. Other chemotherapeutic agents proven to be effective are taxanes such as paclitaxel and docetaxel. Despite of disappointing result of conventional radiotherapy, however, hyperfractionated radiation therapy and combined chemotherapy has been suggested to improve survival rates by some institutions, while others disagree. The dismal results of conventional treatments for ATCs have stimulated the investigation for new therapeutic methods with improved outcome. There have been a number of trials of new materials or therapeutic methods. In recent studies, some trials were partially successful or promising in vitro or in vivo. The examples of these trials are; redifferentiation therapies, molecular targeted therapies, and some other miscellaneous methods. Although the observations may suggest that some of the methods may have a therapeutic effect on ATCs, or may act as an adjunct to other primary treatment modality, the efficacy and safety have not been ascertained yet in human trials, and further confirmation through in-depth studies are required.
Cisplatin ; Doxorubicin ; Humans ; Molecular Targeted Therapy ; Paclitaxel ; Prognosis ; Recurrence ; Survival Rate ; Taxoids ; Thyroid Gland ; Thyroid Neoplasms

The fragmentation pathways of two taxanes drugs have been studied in positive ion mode by Q-TOF with the advantages of high mass accuracy and high resolution analysis. The [M+H] + ions were observed by ESI-MS, from which the molecular weights were obtained. Using the protonated pseudo-molecular ions [M+H]+ as internal reference compounds, the accurate mass and element composition of the fragment ions were determined. The collision induced dissociation (CID) data of the [M+H] ions provided fragmentation pathways of related compounds. Results showed that the major cleavage pathways of paclitaxel and docetaxel were the same that the cleavage of C-O bond between the side chain and taxol skeleton easily occurred, then stripping of the functional groups on the parent ring. Some common fragments were formed, such as m/z 105.033 7, 291.137 3, 309.148 5, 327.159 7, 387.181 2 and 509.217 4, which would provide a basis for future qualitative and quantitative analysis of taxanes in vitro and in vivo.
Paclitaxel ; chemistry ; Peptide Fragments ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Taxoids ; chemistry

Acetates ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; metabolism ; pharmacokinetics ; Biotransformation ; Diterpenes ; metabolism ; Paclitaxel ; metabolism ; Taxoids ; metabolism ; pharmacokinetics

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.
Cell Line ; Cohort Studies ; Drug Resistance ; Genome ; Humans ; Learning ; Machine Learning ; Methods ; Paclitaxel ; Sensitivity and Specificity ; Taxoids

OBJECTIVE: To report on the incidence of nab-paclitaxel hypersensitivity reactions (HSRs) in patients with prior taxane HSR. METHODS: From 2005 to 2015, all patients who received nab-paclitaxel for a gynecologic malignancy were identified. Chart abstraction included pathology, prior therapy, indication for nab-paclitaxel, dosing, response, toxicities including any HSR, and reason for discontinuation of nab-paclitaxel therapy. RESULTS: We identified 37 patients with gynecologic malignancies with a history of paclitaxel HSR who received nab-paclitaxel. Six patients (16.2%) had a prior HSR to both paclitaxel and docetaxel while the other 31 patients had not received docetaxel. No patients experienced a HSR to nab-paclitaxel. Median number of cycles of nab-paclitaxel was 6 (range 2–20). Twelve patients received weekly dosing at 60 to 100 mg/m². The remainder of patients received 135 mg/m² (n=13), 175 mg/m² (n=9), or 225 mg/m² (n=3). Thirty four patients (91.9%) received nab-paclitaxel in combination with carboplatin (n=28, 75.7%), IP cisplatin (n=1, 2.7%), carboplatin and bevacizumab (n=3, 8.1%), or carboplatin and gemcitabine (n=2, 5.4%). Reasons for discontinuing nab-paclitaxel included completion of adjuvant therapy (n=16), progressive disease (n=18), toxicity (n=1), and death (n=1). There were no grade 4 complications identified during nab-paclitaxel administration. Grade 3 complications included: neutropenia (n=9), thrombocytopenia (n=4), anemia (n=1), and neurotoxicity (n=1). CONCLUSION: Nab-paclitaxel is well-tolerated with no HSRs observed in this series of patients with prior taxane HSR. Given the important role of taxane therapy in nearly all gynecologic malignancies, administration of nab-paclitaxel should be considered prior to abandoning taxane therapy.
Albumin-Bound Paclitaxel ; Anemia ; Bevacizumab ; Carboplatin ; Cisplatin ; Drug Hypersensitivity ; Drug Therapy ; Humans ; Hypersensitivity* ; Incidence ; Neutropenia ; Paclitaxel ; Pathology ; Thrombocytopenia

The chemical constituents of Taxus chinensis var. mairei cell cultures were investigated by chromatographic methods, including silica gel column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from the 80% ethanol extract of cultured cells and their structures were elucidated by spectral data and physicochemical properties, which were identified as 2α,4α,7β,9α,10β-pentaacetoxy-14β-hydroxytax-11-ene (1), 2α,4α,7β,9α,10β-pentaacetoxytax-11-ene (2), 1β-deoxybaccatin VI (3), 2α-acetoxytaxusin (4), taxuyunnanine C (5), yunnanxane (6), 2α,5α,10β-triacetoxy-14β-propionyloxy-4 (20), 11-taxadiene (7), 2α,5α,10β-triacetoxy-14β-isobutyryloxy-4 (20), 11-taxadiene (8), 2α,5α,10β-triacetoxy-14β-(2'-methyl)butyryloxy-4 (20), 11-taxadiene (9), 13-dehydroxylbaccatin III (10), 13-dehydroxy-10-deacetylbaccatin III (11), paclitaxel (12) and (13) β-sitosterol. Among them, compound 1 is a new compound, and compounds 2, 4, 10 and 11 are isolated from the cell culture of Taxus chinensis var. mairei for the first time.
Alkenes ; analysis ; Cell Culture Techniques ; Cells, Cultured ; Diterpenes ; analysis ; Molecular Structure ; Paclitaxel ; analysis ; Sitosterols ; analysis ; Taxoids ; analysis ; Taxus ; chemistry