In Vivo Methods for Screening and Preclinical Testing

Corbett, Thomas H.; Valeriote, Fred; LoRusso, Patricia; Polin, Lisa; Panchapor, Chiab; Pugh, Susan; White, Kathryn; Knight, Jennifer; Demchik, Lisa; Jones, Julie L.; Jones, Lynne A.; Lisow, Loretta

doi:10.1007/978-1-4615-8152-9_5

Cited by 58 publications

(33 citation statements)

References 11 publications

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“…Table 2). Any drug resulting in a TGI of !58% (the NCI standard criterion for antitumor activity) was considered as being a valid anticancer agent (26). One mouse showed a partial tumor regression of 53% at the 10 mg/kg peloruside dose.…”

Section: Peloruside Effects On Proliferation Of Cultured Cancer Cellsmentioning

confidence: 99%

Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model

Meyer

Krauth

Wick³

et al. 2015

Molecular Cancer Therapeutics

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Peloruside A is a microtubule-stabilizing agent isolated from a New Zealand marine sponge. Peloruside prevents growth of a panel of cancer cell lines at low nanomolar concentrations, including cell lines that are resistant to paclitaxel. Three xenograft studies in athymic nu/nu mice were performed to assess the efficacy of peloruside compared with standard anticancer agents such as paclitaxel, docetaxel, and doxorubicin. The first study examined the effect of 5 and 10 mg/kg peloruside (QDÂ5) on the growth of H460 non-small cell lung cancer xenografts. Peloruside caused tumor growth inhibition (%TGI) of 84% and 95%, respectively, whereas standard treatments with paclitaxel (8 mg/kg, QDÂ5) and docetaxel (6.3 mg/kg, Q2DÂ3) were much less effective (%TGI of 50% and 18%, respectively). In a second xenograft study using A549 lung cancer cells and varied schedules of dosing, activity of peloruside was again superior compared with the taxanes with inhibitions ranging from 51% to 74%, compared with 44% and 50% for the two taxanes. A third xenograft study in a P-glycoprotein-overexpressing NCI/ADR-RES breast tumor model showed that peloruside was better tolerated than either doxorubicin or paclitaxel. We conclude that peloruside is highly effective in preventing the growth of lung and P-glycoprotein-overexpressing breast tumors in vivo and that further therapeutic development is warranted.

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Section: Peloruside Effects On Proliferation Of Cultured Cancer Cellsmentioning

confidence: 99%

Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model

Meyer

Krauth

Wick³

et al. 2015

Molecular Cancer Therapeutics

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“…Tumor weight was calculated from two dimensional measurements (mm) [17]: Tumor weight = length x width 2 / 2. The ratio between the mean tumor weight of treated mice and that of control mice x 100 (T/C%) was assessed on each day of measurement.…”

Section: Evaluation Of Anti-tumor Activitymentioning

confidence: 99%

Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma

Stefano

Raspaglio

Zannoni

et al. 2009

Biochemical Pharmacology

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This study was aimed at evaluating the potential application of benzophenanthridine alkaloids, sanguinarine and cheleritrine, in the therapy of melanoma cancer. In vitro antiproliferative activity of sanguinarine was higher than that of cheleritrine against the B16 melanoma 4A5 cells. Both agents were able to produce DNA breaks, and the DNA unwinding assay showed that they act as DNA intercalating agents. Sanguinarine was selected for determination of its in vivo preclinical efficacy. Oral treatment with sanguinarine reduced the tumor burden in a transplantable murine tumor grown in a syngenic host (B16 melanoma 4A5 in C57BL/6 mice), and in a human tumor xenograft grown in immunodeficient mice (A375 human melanoma in athymic nude mice). In A375 tumors a significant decrease in the proliferation marker Ki67, and a reduction in the activated mitogen-activated protein kinases (p-p44/42 MAPK), and in protein kinase B (pAKT) were also observed. Three out of eleven A375-bearing treated mice were tumor-free at the end of treatment, and did not develop any tumor after a further, treatment-free, observation period of 60 days. Sanguinarine also showed a striking anti-angiogenic activity in mice. Data from the present study support the concept that sanguinarine can be effective in melanoma skin cancer.

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“…The tumor weight was calculated from two-dimensional measurements (mm; Corbett et al 1997): Tumor weightZlength!width 2 /2. Differences in efficacy between treatment groups were expressed as the percentage of maximum tumor weight inhibition (TWI%).…”

Section: Evaluation Of Anti-tumor Activitymentioning

confidence: 99%

Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 in an experimental model of estrogen-dependent breast cancer

Gallo¹,

Mantuano²,

Fabrizi³

et al. 2007

Endocr Relat Cancer

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The study reported here was designed to determine whether a phytoestrogen-containing soy extract (SSE) could negate/overwhelm the inhibitory effects of ICI 182 780 on the growth of estrogen-sustained human breast cancer xenografts (MCF-7), in ovariectomized athymic mice. As expected, estradiol-supplemented tumors did not grow over the study period in ICI 182 780-treated females; concomitant administration of 50 mg/kg per day SSE slightly potentiated the inhibitory activity of the drug, while at 100 mg/kg per day, SSE partially negated ICI 182 780 activity. In keeping with these in vivo outcomes, we observed that the level of cyclin D1 (and progesterone receptor) in MCF-7 xenografts was considerably reduced by ICI 182 780, an effect enhanced by concomitant treatment with 50 SSE, but reduced by the higher dosage (i.e. 100 mg/kg per day). Thrombospondin-1 (TSP-1) and kallikrein 6 (KLK6) levels were also reduced following ICI 182 780, although to a lesser degree; again, combined anti-estrogen and SSE produced a dose-dependent regulation in TSP-1 and KLK6 tumor level, with a further reduction in the mRNA gene expression at 50 SSE (compared with ICI 182 780) and a partial reversion of the drug-induced down-regulation at 100 mg/kg per day. No modulation was detected in the serum concentration of IGF-1 (a potent mitogen for estrogen receptor-positive breast cancer cell lines) either upon treatment with ICI 182 780 or concomitant administration of the anti-estrogen with SSE. In conclusion, results from this study raise concerns about the consumption of isoflavone supplements in conjunction with ICI 182 780 therapy, in postmenopausal women with estrogendependent breast cancer.

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In Vivo Methods for Screening and Preclinical Testing

Cited by 58 publications

References 11 publications

Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model

Peloruside A Inhibits Growth of Human Lung and Breast Tumor Xenografts in an Athymic nu/nu Mouse Model

Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma

Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 in an experimental model of estrogen-dependent breast cancer

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