Productions of Taxol and Related Taxanes by Cell Suspension Cultures of Taxus yunnanensis

A high taxol yield cell line of Taxus yunnanensis Cheng et L. K. Fu keeps a high taxol_producing level after successive subcultures for more than eight years. In this study, eight taxanes were isolated from the suspension cell cultures of this cell line. Based on NMR and MS analyses, and comparison with literature data and standards, their structures were determined to be 2α,5α,10β_triacetoxy_14β_propionyloxy_4(20),11_taxadiene (1), 2α,5α,10β_triacetoxy_14β_(2′_methyl)_butyryloxy_4(20),11_taxadiene (2), 2α,5α,10β_14β_tetra_acetoxy_4 (20),11_taxadiene (3, taxuyunnanine C), 2α,5α,10β_triacetoxy_14β_(2′_methyl_3′_hydroxy)_butyryloxy_4(20),11_taxadiene (4, yunnanxane) and its 3′_epimer (5), baccatin Ⅳ (6), baccatin Ⅲ (7) and taxol (8), respectively. Among those compounds, 3, 5, 6 and 7 were reported to be isolated from the suspension cell cultures of T. yunnanensis for the first time. TLC and HPLC analyses indicated that the chemical constituents of the culture solution were similar to those of cultured cells. Moreover, the highest taxol content of this cell line reached 0.3% and the cell line could be applied for a large_scale culture.

Non-platinum-based chemotherapy for treatment of advanced gastric cancer:5-fluorouracil,taxanes,and irinotecan

Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.

Breakthrough therapy for peritoneal carcinomatosis of gastric cancer:Intraperitoneal chemotherapy with taxanes

The effect of chemotherapy on peritoneal carcinomatosis(PC) of gastric cancer remains unclear.Recently,the intraperitoneal(IP) administration of taxanes [e.g.,paclitaxel(PTX) and docetaxel(DOC)] during the perioperative period has shown promising results.Herein,we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results.IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h.The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects,making it ideal for IP chemotherapy.There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy(SPIC).In SPIC,patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery(CRS) until disease progression.Usually,a taxane dissolved in 500-1000 m L of saline at ordinary temperature is administered through an IP access port on an outpatient basis.According to phase Ⅰ?studies,the recommended doses(RD) are as follows: IP DOC,45-60 mg/m2; IP PTX [without intravenous(IV) PTX],80 mg/m2; and IP PTX(with IV PTX),20 mg/m2.Phase Ⅱ studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%.A phase Ⅲ study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011.The prognosis of patients who underwent CRS was better than that of those who did not; however,this was partly due to selection bias.Although several phase Ⅱ studies have shown promising results,a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

Unfavorable Pathological Complete Response Rate of Neoadjuvant Chemotherapy Epirubicin plus Taxanes for Locally Advanced Triple-negative Breast Cancer

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer （TNBC）. Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m^2 plus paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response （pCR）, which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival （RFS） and overall survival （OS） were secondary endpoints. Thirty-nine （90.7%） patients were at clinical stages II B-IIIC. Thirty-seven （86%） completed 4-6 cycles of preop- erative chemotherapy, and objective response rate （ORR） was 81.4% （35/43）. Forty-two patients un- derwent radical surgery subsequently. The pCR rate was 14.3% （6/42）. The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting （88.4%, 38/43） and neutropenia （88.4%）. After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally ad- vanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

A Highly Regioselective Deacetylation of Taxanes

A highly regioselective O-deacetylation of taxanes at C-5 position was accomplished by treatment with t-BuOK and a possible mechanism was proposed.

A New Abeotaxane Diterpenoid from the Seeds of Taxus mairei

A new abeotaxane was isolated from the seeds of Taxus mairei. Its structure was determined to be 2α, 5α, 13α-trihydroxy-7β, 10β-diacetoxy-2（3→20） abeotaxa-4（20）, 11-dien-9- one on the basis of 1D and 2D spectral analysis.

Clinical Implications of HER-2 and P53 in Taxane-Based and Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer

OBJECTIVE To evaluate the predictive value of humanepidermal growth factor receptor-2 (HER-2) and P53 in taxane-based and anthracycline-based neoadjuvant chemotherapy (NAC)in breast cancer.METHODSSixty-two patients with breast cancer wereincluded in this study.Twenty-two patients were treated withtaxane-based (taxane group) and 40 with anthracycline-based(anthracycline group).ER,PR,c-erbB2 and P53 were detected byimmunohistochemistry staining before NAC,and FluorescenceIn Situ Hybridization(FISH) was used to detect the HER-2 geneamplification for the cases with the expression of c-erbB2 proteinas (++) or (+++).The efficacy of the regimens was evaluated afterNAC.RESULTS In the anthracycline group,objective response (OR)was observed in 30 out of 40 patients (75%),whereas no response(NR) was observed in 10 patients (25%).In the taxane group,ORwas observed in 15 patients out of 22 patients (68.2%),whereasNR was observed in 7 patients (31.8%).HER-2-negative status wascorrelated with a high OR in both taxane-based and anthracycline-based NAC (P = 0.023 and P = 0.029),whereas P53-negative statuswas correlated with high OR rate in anthracycline-based NAC (P= 0.041).The significant difference of the CR rates was observedbetween the patients took<4 cycles and>4 cycles NAC (4.65% vs.21.05%,P<0.05).CONCLUSION The patients with HER-2 gene non-amplicationmay be sensitive to both taxane-based and anthracycline-basedchemotherapy;the patients without P53 overexpression maysuitable to select anthracycline-based chemotherapy;and properincreased NAC cycles may increase CR rates.

A New Deoxygenation Method for Taxanes Using Hypophosphorous Acid

An efficient and practical radical chain deoxygenation method by phosphorus centered radicals generated from hypophosphorous acid was developed in the synthesis of analogues of paclitaxel.

Role of taxanes in pancreatic cancer

Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.

An Unusual Formation of Cyclic Sulfite at C-4 and C-5 Positions of Taxane

An unusual formation of cyclic sulfite at C-4 and C-5 positions of taxane was accomplished by treatment of compound 1 with excess MeSO2Cl/Et3N and a possible mechanism was proposed.

Reduction of 1-Deoxy-13-oxotaxanes

Reduction of 1-deoxy-13-oxotaxanes has been studied under different reaction conditions. Some interesting reactions were reported.

New Taxane Diterpenoids from Taxus yunnanensis

Three hitherto unknown taxane diterpenoids,namely baccatin Ⅷ(1),baccatin Ⅸ(2),and baccatin Ⅹ(3),along with 10 known analogues were isolated from an ethanolic extract of the twigs and leaves of Taxus yunnanensis.The new structures were characterized based on extensive spectroscopic analysis.Compounds 1 and 2 were tested for their in vitro cytotoxicity against five human tumor cell lines,and 1 exhibited inhibitory effects on HL-60 and MCF-7,with IC_(50) values of 3.44 and 9.67 μM,respectively.

NEW TAXANES FROM TAXUS CHINENSIS.2

Tow new taxane diterpenes were isolated from the leaves and stems of Taxus chinensis.Thcir structures were established as 2-deacctyl-5-decinnamatetaxagifine and taxagifinc Ⅲ on the basis of spectroscopic analysis.

TAXAYUNTIN A,B,C AND D----FOUR NEW TETRACYCLIC TAXANES FROM TAXUS YUNNANENSIS

Four new taxane diterpenoids were isolated from the bark of Taxus yunnanensis.Their structures were elucidated as the new skeleton with 5/7/6/4 membered rings by spectral analysis and 2D NMR shift correlation experiments.

YUNNANXOL AND YUNNANXAHINE——TWO NEW TETRACYCLIC TAXANE DITERPENOIDS FROM TAXUS YUNNANENSIS

Two new tetracyclic taxane diterpenoids----yunnanxol(1) and yunnanxamine(2)have been isolated from the bark of Taxus yunnanensis Cheng et L.K.Fu.Their structures have been established from the spectral data,mainly from MS,highfield ~1H NMR,~1H-~1H COSY, ^(13)C NMR,^(13)C-~1H COSY and ^(13)C-~1H COLOC spectroscopies.

TAXAYUNTIN,A NEW TETRACYCLIC TAXANE FROM THE LEAVES OF TAXUS YUNNANENSIS

A new skeleton taxane diterpene,taxayuntin,was isolated from the leaves and stems of Taxus yunnanensis.Its structure was determined by spectroscopic methods(MS,~1H NMR,^(13)C NMR, ~1H-~1H COSY,~1H-^(13)C COSY and ^(13)C-~1H COLOC)and X-ray diffraction.

抗Taxane的新机制

据美国BIOCOMPARE科技新闻网（2006／7／21）报道，斯坦福大学Stanley N．Cohen博士实验室的Chih·Jian Lih和其同事，研究人员利用一种可以随机改变哺乳动物细胞之基因表现的方法，以及可以检测改变的基因功能之筛选方法，确定出之前从未确定出的基因txr1。前列腺癌细胞中，这种基因表现的增加会导致患者对于taxane药物的抗性。Taxanes是一类广泛使用的化疗药物，商品名为docetaxel和paclitaxel。这类药物可以抑制微管降解和之后细胞分裂，以阻止癌细胞的生长。

Optic Nerve Metastasis from Breast Carcinoma after Treatment with Taxanes

Introduction: The incidence of ocular metastasis from Breast Carcinoma is only between 5% - 30%, mainly located in choroid, but the location in optic nerve is even more infrequent. We present a rare case that combined both locations sequentially in the same eye. Methods: Case report. Results: A 58-year-old woman with advanced breast cancer was referred with a choroidal metastasis in her right eye which responded well to systemic Taxol and Avastin. Afterwards, she developed an optic nerve metastasis in the same eye when she was under the treatment, so it was changed to Docetaxel. Unfortunately the patient didn’t respond to this treatment and died. Conclusions: Choroidal metastasis secondary to breast cancer generally responds well to radiotherapy. Even so, in cases that a great deterioration of visual acuity is expected after radiation, chemotherapy like taxanes is an alternative to preserve vision with complete tumor regression. Nevertheless, the presentation of a second metastasis in optic nerve can be indicative of inadequate treatment of metastatic disease or complication of the treatment, or both.

Pseudocirrhosis after the Use of Taxanes and Bevacizumab in Metastatic Breast Cancer： Case Reports

Currently, multiple lines of cytotoxic chemotherapy for treatment of metastatic breast cancer are available, and Taxanes, used as monotherapy or in combination with anti-angiogenic drugs, such as Bevacizumab, are one of the most used schemes in clinical practice. These drugs have different side effects and the liver is one of the most affected organs. The objective of this paper is to report three cases of metastatic breast cancer with positive expression of hormone receptors and without amplification of HER-2 protein that were treated with Taxane and Bevacizumab, developed pseudocirrosis probably caused by these drugs and died due to liver failure. It can be drawn from the study that liver failure, as a pseudocirrhosis evolution, is an unusual but lethal event that may occur during the treatment of metastatic breast cancer with Taxanes and Bevacizumab. This warns the importance of diagnostic suspicion of this pathology.

Two New Taxane Diterpenoids from Taxus Chinensis

Two new taxane diterpenoids, 2-deacetoxy-7,9-dideacetyltaxinine J (1) and 2-deacetoxytaxinine B (3), were isolated from the barks of Taxus chinensis. Their structures were elucidated by spectroscopic methods.