• KSBB Journal
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• 제11권3호
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• pp.323-328
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• 1996

Diterpenoid 생합성의 중요한 전구체인 geranyl­g geranyl pyrophosphate의 공급을 위해 외부에서 geraniol을 넣어 주었을 때 taxol을 포함한 일부 taxane의 생산이 증대 됨을 알 수 있었다. 또한 투여 시기와 투여량에 따라 결과가 크게 변화하였다. Camphor와 menthol은 taxol과 같은 terpenoid 계열의 물질이지만 외부에서 공급하였을 때에는 taxol 생산을 증대시키는 효과는 없었다. 외부에서 인위적으로 taxol과 cephalomannine, baccatin ill 를 공급했을 때 모든 경우에서 taxal 생산은 자극받지 않았으며 taxal을 공급했을 경우에는 bacca tin ill 의 생산이, cephalamannine을 공급했을 경우에는 7 -epl- 1 Q-deacetyltaxol의 생산이, 그리고 baccatin ill을 공급했을 경우에는 10-deacetyltaxol의 생산이 각각 가장 많이 중대하였다.

• 식물조직배양학회지
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• 제27권5호
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• pp.401-405
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• 2000

Influence of fructose addition to the cultivation medium on the production of taxanes and the growth of callus culture of Taxus baccata was studied. The cultures showed an ability to adjust to the substitution of some of the sucrose in the media by fructose and the fresh biomass accumulation was higher on the media containing different concentrations of fructose during the second cultivation period.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.775-781
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• 2015

Background: RB1 (retinoblastoma 1) was reportedly one of the major determinative factors for sensitivity to taxanes in previous studies. In this study, we investigated the influence of RB1 single nucleotide polymorphisms (SNPs) on the efficacy of platinum-taxane regimens in advanced NSCLC patients. Materials and Methods: 234 cases of patients with advanced NSCLC who were treated with first-line platinum-taxane agents were enrolled in this study. Genomic DNA was extracted from patients' peripheral blood samples using a QIAamp DNA Maxi Kit, and genotyped by iSelect HD Bead-Chip. Results: Regression analyses were conducted through the univariate and multivariate Cox proportional hazards model in the 234 patients. The results showed that of the eight RB1 tagSNPs, only rs4151510 was a positive predictive factor for the advanced NSCLC patients treated with platinum taxanes regimen. The patients with G/G genotype of RB rs4151510 had longer overall survival (OS) than the non-G/G genotype (p=0.018). The histology was also correlated with OS in the whole advanced NSCLC patients. Three tagSNPs of RB1, rs4151510, rs4151465, rs9568036 were significantly associated with OS in the advanced NSCLC patients with squamous cell histology using Kaplan-Meier overall survival analysis stratified by histology. Conclusions: RB1 genomic variants were correlated with the efficacy of platinum-taxanes regimen. RB rs4151510 is an independent factor of the prognosis of NSCLC patients receiving platinum-taxane chemotherapy.

• 한국동물학회:학술대회논문집
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• 한국동물학회 1994년도 한국생물과학협회 학술발표대회
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• pp.186.2-186
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• 1994

No Abstract, See Full Text

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9939-9943
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• 2014

Lobaplatin, one of the third - generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in - vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in - vitro antitumor activities were evaluated with cisplatin - sensitive and cisplatin - resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with $IC_{50}$ values from 0.9 to $13.8{\mu}mol/L$ in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum - sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum - resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.

• Journal of Microbiology and Biotechnology
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• 제27권8호
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• pp.1379-1385
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• 2017

The content of taxol in the bark of yews is very low, and this is not affordable from the environmental point of view. Thus, it is a necessity to look for alternative sources of taxol production to solve its supply. Currently, a large portion of the taxol in the market comes from chemical semi-synthesis, but the semi-synthetic precursors such as baccatin III and 10-deacetyl-baccatin III are extracted from needles and twigs of yew trees. Taxol-producing fungi as a renewable resource is a very promising way to increase the scale of taxol production. Our group has obtained a taxol-producing endophytic fungus, Aspergillus niger subsp. taxi HD86-9, to examine if A. niger can produce the taxanes. Six compounds from the fermentation broth of strain HD86-9 were isolated and identified by $^1H$ NMR, $^{13}C$ NMR, and ESI-MS. The results showed that the six compounds included four taxane diterpenoids (taxol, cephalomannine, baccatin III, and 10-deacetyl-baccatin III) and two non-taxane compounds (${\beta}-sitosterol$ and flavonoid isovitexin). The study verified that the taxanes can be produced by the A. niger, which is very important to taxol production via chemical semi-synthesis. Additionally, the finding is potentially very significant to solve the taxol semi-synthetic precursors extracted from needles and twigs of yew trees, and the precursor production can be easily increased through the culture condition optimization, genetic breeding, and metabolic engineering of the A. niger.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.65-69
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• 2015

Background: To evaluate the impact of adding taxanes to anthracycline-based regimens in the adjuvant setting in localized young female breast cancer patients on the overall survival (OS) and the disease free survival (DFS). Materials and Methods: This retrospective study included all female breast cancer patients who were candidates for adjuvant chemotherapy presenting to Kasr Al Ainy centre of clinical oncology and Cairo oncology centre (Cairo Cure) in the period from January 2005 till December 2010. Results: Our study included 865 patients, 732 of whom received anthracycline based regimens and 133 taxane based regimens. The mean age of patients was 39 years. After a median follow up of 50 months the median DFS was 48.4 months. Survival analysis indicated that the tumor size (>5cm vs. <5cm) p=0.001), nodal involvement (Yes vs. No) p=0.0001) and pathology (invasive lobular vs. ductal) p=0.048) affected DFS. As regards hormonal status, ER, PR and HER 2neu positive patients had longer DFS (p=0.001, 0.003, 0.106). On multivariate analysis DFS was affected by tumor size and lymph node involvement (p=0.014, 0.007). Subgroup analysis showed improvement in arms treated with taxanes in terms of DFS with positive Her2neu, ER and PR, but this was not statistically significant. Conclusions: Adding adjuvant taxanes to anthracyclines is beneficial for treatment of localized breast cancer among all subgroups, especially higher risk groups. The type of adjuvant chemotherapy regimens and tumor characteristics have direct effects on DFS.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.413-417
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• 2013

Purpose: This phase II study was undertaken to determine the efficacy and safety of Loubo$^{(R)}$ (Lobaplatin) in combination with pemetrexed in treating patients with metastatic breast cancer who failed to respond to anthracycline or taxanes. Patients and Methods: Metastatic breast cancer cases who had previously received an anthracycline and a taxane in either adjuvant or metastatic settings, were enrolled. All patients were recruited from Jiangsu Cancer Hospital and Research Institute, and were treated with Loubo$^{(R)}$ (Lobaplatin) 35 $mg/m^2$ (intravenous; on day 1) and pemetrexed 500 $mg/m^2$ (intravenous; on day 1) every 21 days. Efficacy and side effects were evaluated after at least two cycles of chemotherapy. Results: All eligible 19 patients completed at least 2 cycles of chemotherapy with pemetrexed and lobaplatin, and were evaluable. Overall, 3 (15.8%) patients achieved partial response, 11 (57.9%) stable disease, 5 (26.3%) progression of disease, with no complete remission. Response rate was 15.8%, disease control rate was 42.1%. The median survival time was 10.3 months. Neutrophil suppression occurred in 36.8% of patients who had grade 2 toxicity, and 26.3% had grade 3, 26.4% had grade 4. Thrombocytopenia was encountered as follows: 21.1% grade 2, 15.8% grade 3 and 5.5% grade 4. Incidences of anemia were 10.5% in grade 2, 5.3% grade 3 and 0% grade 4. Only 5.3% of patients required packed red blood cell transfusion. Grade 3 digestive tract toxicity occurred in 5.5% of patients. Other toxicities included elevated transaminase,oral mucositis and skin rashes. Conclusions: The regimen of lobaplatin and pemetrexed is modestly active in metastatic breast cancer patients who failed anthracycline or taxanes, and the toxicity profile suggesting that the doses of chemotherapy should be further modified.

• KSBB Journal
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• 제11권3호
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• pp.263-269
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• 1996

유럽 주목(Taxus baccata Pendula) 의 세포배양에 서 추출한 taxol 전구체 baccatin ill를 이용하여 항암제 taxol을 반합성할 수 있었다. 유럽주목의 캘러 스배양과 현탁배양 모두에셔 baccatin ill의 생성을 확인할 수 있었으며 함량은 건조중량 기준으로 평균 0.015%(w/w)에 달하였다. Taxol의 반합성은 세포 배양에서 생성된 baccatin ill에 taxol side chain을 합성시킴으로서 가능하였다. Taxol side chain을 합 성하기 위하여 (S)-(+)-phenylglycine로부터 (-) - -N-(S)-2-hydroxy-l-phenyl ethyl)benzamide를 합성하였고 다음 단계로 (-)-N-(lS,2S)-2-hy­d droxy-l-phenyl-3-butenyl) benzamide를 합성하 였고 최종적으로 산화과정을 거쳐 taxol side chain 인 (2R,3S) - (-) -2-(1-ethoxyethoxy)-3-phenyl-3 (phenylmethanamido) propanoic acid를 얻을 수 있었다. 이러한 반합성 과정을 통하여 0.0002 % 수준의 taxol 및 0.0005 %의 관련 taxane을 합성하였다. 이와 같이 주목 세포배양을 이용한 taxol 반합성 방법은 기존의 주목 잎에서 추출한 baccatin ill를 이용하는 방법에 비하여 충분한 경제성이 있을 수 있으며 이에 따라 taxo!의 새로운 공급원의 역할 및 기타 여러 종류의 taxol 유사체의 효율적인 이용 등 앞으로 기대 효과가 크다고 본다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1471-1477
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• 2015

Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.