Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

Vassileva, Vessela; Moriyama, Eduardo H.; Souza, Raquel De; Grant, Justin; Allen, Christine; Wilson, Brian C.; Piquette-Miller, Micheline

doi:10.1038/sj.bjc.6604803

Cited by 41 publications

(54 citation statements)

References 32 publications

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“…We have previously shown that the complete elimination of these intervals through a continuous chemotherapy approach leads to a substantial improvement in ovarian cancer tumor suppression over intermittent administration (13,37). Similarly, the present study highlights that continuous docetaxel therapy leads to significantly greater antitumor efficacy than intermittent administration in HeyA8 xenografts.…”

Section: Discussionsupporting

confidence: 58%

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Souza

Zahedi

Badame

et al. 2011

Molecular Cancer Therapeutics

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Drug resistance leads to chemotherapy failure and is responsible for the death of a great majority of patients with metastatic, late-stage ovarian cancer. The present study addressed whether changes in the chemotherapy dosing schedule affect the development, further worsening, or circumvention of drug resistance in chemosensitive and chemoresistant ovarian cancer. Severe combined immunodeficient mice bearing HeyA8 and HeyA8-MDR xenografts were treated with docetaxel intermittently (1Â/wk or 3Â/wk) or continuously for 21 days. Tumor mRNA expression of genes implicated in docetaxel resistance was measured by quantitative real-time-PCR. Analyzed genes included those encoding for the drug efflux transporters mdr1 and mrp7 and for molecules that interfere with or overcome the effects of docetaxel, including b-tubulinIII, actinin4, stathmin1, bcl2, rpn2, thoredoxin, and akt2. In both models, continuous docetaxel resulted in greater antitumor efficacy than 1Â/wk or 3Â/wk dosing and did not induce upregulation of any analyzed genes. Once weekly dosing caused upregulation of various drug resistance-related genes, especially in chemoresistant xenografts. More frequent, 3Â/wk dosing diminished this effect, although levels of various genes were higher than for continuous chemotherapy. Drug efflux transporter expression was further examined by Western blotting, confirming that intermittent, but not continuous, docetaxel induced significant upregulation. Overall, our results show that the presence and length of treatment-free intervals contribute to the development of drug resistance. Elimination of these intervals by continuous dosing resulted in superior antitumor efficacy and prevented drug resistance induction in chemosensitive and chemoresistant disease. These results encourage the clinical implementation of continuous chemotherapy to overcome and/or prevent drug resistance in newly diagnosed and recurrent, refractory ovarian cancer.

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Section: Discussionsupporting

confidence: 58%

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Souza

Zahedi

Badame

et al. 2011

Molecular Cancer Therapeutics

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“…injection of sterile saline. On days 7, 10, 14, 17, 21, and 24 postinoculation, tumor burden was assessed by bioluminescence as before (13). Animals were monitored as described above.…”

Section: Antitumor Efficacy Of Continuous and Intermittent Dtx In Skomentioning

confidence: 99%

“…For bioluminescence imaging, SKOV3 cells were transfected with the luciferase gene (SKOV3-luc) and bioluminescence-viability correlation was done as before (13). The murine ovarian cancer cell line ID8 was a kind gift from Dr. Jim Petrik (University of Guelph, Ontario, Canada; ref.…”

Section: Cell Linesmentioning

confidence: 99%

“…We previously developed an implantable polymer-lipid film capable of continuous release of paclitaxel, which showed efficacy in an ovarian cancer xenograft model (13,14). The need for surgical implantation and slow biodegradation led to the development of an injectable paste with similar properties composed of chitosan, phospholipids, and laurinaldehyde, termed PoLi gel , which showed good biocompatibility and biodegradation (15,16).…”

Section: Introductionmentioning

confidence: 99%

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Continuous Docetaxel Chemotherapy Improves Therapeutic Efficacy in Murine Models of Ovarian Cancer

Souza

Zahedi

Moriyama

et al. 2010

Molecular Cancer Therapeutics

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Ovarian cancer is known as the silent killer for being asymptomatic until late stages. Current first-line treatment consists of debulking surgery followed by i.v. chemotherapeutics administered intermittently, which leads to insufficient drug concentrations at tumor sites, accelerated tumor proliferation rates, and drug resistance, resulting in an overall median survival of only 2 to 4 years. For these reasons, more effective treatment strategies must be developed. We have investigated a localized, continuous chemotherapy approach in tumor models of human and murine ovarian cancers using the antineoplastic agent docetaxel. We show here that continuous docetaxel therapy is considerably more efficacious than intermittent therapy, resulting in a greater decrease in tumor burden and ascites fluid accumulation. Immunohistochemical analyses show that continuous chemotherapy abrogates tumor cell proliferation and angiogenesis to the tumor microenvironment, leading to greater tumor cell death than intermittent docetaxel therapy. Overall, our results show greater therapeutic advantages of continuous over intermittent chemotherapy in the treatment of ovarian cancer.

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“…Briefly, 2 · 10 6 cells were injected into the spleen, followed by a splenectomy after 10 min (21,22). Hepatic tumor growth was monitored by bioluminescence imaging using the IVIS system (Xenogen/Caliper Life Sciences) as previously described (23). The Living Image Software (Xenogen/Caliper Life Sciences) was used to obtain and analyze images.…”

Section: Cell Linesmentioning

confidence: 99%

Significant Therapeutic Efficacy with Combined Radioimmunotherapy and Cetuximab in Preclinical Models of Colorectal Cancer

et al. 2015

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Despite extensive efforts to improve the clinical management of patients with colorectal cancer, approved treatments for advanced disease offer limited survival benefit. Therefore, the identification of novel treatment strategies is essential. We evaluated the preclinical efficacy of combination radioimmunotherapy, using a humanized 131 Ilabeled anti-carcinoembryonic antigen antibody ( 131 I-huA5B7), with cetuximab in colorectal cancer (CRC). Methods: Three human CRC cell lines-SW1222, LoVo, and LS174T-were used to generate subcutaneous xenografts, and stably luciferase-transfected SW1222 cells were used to establish a model of hepatic metastases in immunocompromised mice. Imaging and biodistribution studies were conducted to confirm the selective tumor localization of 131 I-huA5B7. Efficacy was evaluated on the basis of tumor growth delay and survival, along with markers of DNA damage response, cell cycle, proliferation, and apoptosis. Results: Selective tumor targeting was achieved with 131 IhuA5B7 alone or in combination with cetuximab without observable toxicity. Compared with monotherapy, combining cetuximab with radioimmunotherapy significantly and synergistically reduced tumor growth and prolonged survival of mice in 2 of the subcutaneous and in the metastatic tumor model. Evidence of DNA damage, G2/M arrest, significantly decreased proliferation, and increased apoptosis were observed with radioimmunotherapy and the combination therapy. However, a significant decrease in DNA-protein kinase expression with the combination regimen suggests that the addition of cetuximab suppressed DNA repair. Conclusion: Our results demonstrate enhanced therapeutic efficacy with the combination of cetuximab and radioimmunotherapy in CRC, which could potentially translate into successful clinical outcomes. This strategy could improve the treatment of residual disease postoperatively and ultimately prevent or delay recurrence. Furthermore, other carcinoembryonic antigen-expressing malignancies could also benefit from this approach.

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Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

Cited by 41 publications

References 32 publications

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Chemotherapy Dosing Schedule Influences Drug Resistance Development in Ovarian Cancer

Continuous Docetaxel Chemotherapy Improves Therapeutic Efficacy in Murine Models of Ovarian Cancer

Significant Therapeutic Efficacy with Combined Radioimmunotherapy and Cetuximab in Preclinical Models of Colorectal Cancer

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