The range of optimal concentration and mechanisms of paclitaxel in radio-enhancement in gastrointestinal cancer cell lines

Toiyama, Yuji; Inoue, Yasuhiro; Hiro, Junichiro; Ojima, Eiki; Watanabe, Hideki; Narita, Youhei; Hosono, Atuko; Miki, Chikao; Kusunoki, Masato

doi:10.1007/s00280-006-0327-1

Cited by 15 publications

(9 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The values of minimum efficacious concentration and toxic concentration for paclitaxel used in the present work, c eff = 1 × 10 −5 mol m −3 and c tox = 1 × 10 −2 mol m −3 , are in agreement with [45]. These values are based on the work of [46] who studied the inhibitory effect of paclitaxel on cancer cells. This value of the minimum efficacious concentration is in good agreement with earlier work of [47], who reported prolonged inhibition of human arterial SMCs growth at a medium concentration of 1 × 10 −4 mol m −3 with an IC 50 value for paclitaxel on human arterial SMC growth of 2 × 10 −6 mol m −3 .…”

Section: Methodssupporting

confidence: 87%

Optimization of Drug Delivery by Drug-Eluting Stents

et al. 2015

View full text Add to dashboard Cite

Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

show abstract

Section: Methodssupporting

confidence: 87%

Optimization of Drug Delivery by Drug-Eluting Stents

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In addition to cisplatin, other chemotherapy drugs may interfere with ERCC1 expression. An in vitro study has shown that radiation activates ERCC1 expression in gastrointestinal cancer cell lines, but not in the same cell lines treated with paclitaxel prior to radiation, suggesting that paclitaxel may suppress ERCC1 (19). In a clinical study performed in ovarian cancer patients treated with cisplatin with or without paclitaxel (20), high levels of ERCC1 mRNA were associated with greater risk of disease progression.…”

Section: Discussionmentioning

confidence: 99%

Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy

Kim

et al. 2010

APMIS

View full text Add to dashboard Cite

Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. Recent reports have suggested that ERCC1 is a predictive and prognostic marker in solid cancers treated with platinum-based chemotherapy. We performed this study to determine whether or not immunohistochemical expression of ERCC1 can predict objective tumor response and cancer-specific survival in patients with advanced urothelial carcinoma treated with cisplatin-based chemotherapy. We performed a retrospective analysis of 89 patients with advanced or recurrent urothelial cancer, who had undergone treatment at Samsung Medical Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89 patients with a known tumor response were available. ERCC1 expression was assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was positive in 49 patients (55%). The overall response rate after chemotherapy was 68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1-positive patients (p = 0.03); the difference in overall survival between patients with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not statistically significant. Other than ERCC1 expression, there was no independent prognostic factor for PFS. These results suggest a negative contribution by ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with cisplatin-based chemotherapy.

show abstract

“…This finding may be explained by the results of an in vitro experiment by Toiyama et al (40). Their research group has shown that radiations activate ERCC-1 expression in gastrointestinal cancer cells, but not in the same cells previously treated with paclitaxel, suggesting that paclitaxel blocks ERCC-1 activity, inhibits the DNA repair system and prevents cellular resistance to drug-induced DNA damage.…”

Section: Mthfr C677t Polymorphism and Methotrexatementioning

confidence: 68%

‘Genetic profiling’ and ovarian cancer therapy (Review)

et al. 2011

View full text Add to dashboard Cite

Abstract. High variability observed among ovarian cancer patients in response to the same therapy and the related toxicity may be correlated to gene polymorphisms and genetic alterations affecting the metabolism of drugs commonly used to treat this tumor. Recent studies have shown a correlation between the polymorphisms characterizing GSTM1-T1 detoxifying enzymes and poor outcome in advanced ovarian cancer patients treated with platinum/paclitaxel-based chemotherapy. Multidrug resistance 1 (mdr-1) polymorphisms were found to be associated with resistance to paclitaxel treatment. Polymorphisms of MRP2, a protein involved in methotrexate, cisplatin and irinotecan active metabolite glucuronide transport, negatively affect platinum-based chemotherapy response. A similar occurrence has been observed with CYP1A1 Ile462Val and ercc1 C118T polymorphisms while patients who were carriers of MTHFR C677T polymorphism had a better response to methotrexate therapy, but an elevated risk of toxicity. Biological therapy with Bevacizumab, the anti-vascular endothelial growth factor has been shown to be less efficient in ovarian cancer patients carrying the polymorphism of the Interleukin-8 gene. Instead, polymorphisms in the XPD gene (Lys751Gln and Asp312Asn), a member of the nucleotide excision repair pathway, positively affects the response to therapy with carboplatin/paclitaxel. Therefore, the study of 'genetic profiling' is crucial to improving the clinician's ability to tailor effective therapy to the molecular profile of the patient while minimizing toxicities. This review describes clinical applications of the above genetic polymorphisms in ovarian cancer patients treated with platinum/paclitaxel-based chemotherapy.

show abstract

The range of optimal concentration and mechanisms of paclitaxel in radio-enhancement in gastrointestinal cancer cell lines

Cited by 15 publications

References 28 publications

Optimization of Drug Delivery by Drug-Eluting Stents

Optimization of Drug Delivery by Drug-Eluting Stents

Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy

‘Genetic profiling’ and ovarian cancer therapy (Review)

Contact Info

Product

Resources

About