Effect of perductal paclitaxel exposure on the development of MNU-induced mammary carcinoma in female S–D rats

Okugawa, Homa; Yamamoto, Daigo; Uemura, Yoshiko; Sakaida, Noriko; Tanano, Akihide; Kamiyama, Yasuo

doi:10.1007/s10549-004-6455-6

Cited by 29 publications

(21 citation statements)

References 20 publications

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“…Tumor development was followed at weekly intervals. Tumors > 10 mm 3 and those that showed a progressive increase in size were scored. Intraductal administration of PLD significantly (P < 0.001, Table 2) protected animals against tumor formation Figure 1.…”

Section: Model I: Mnu-induced Rat Mammary Tumor Modelmentioning

confidence: 99%

“…SpragueDawley rats (n = 12) were administered MNU (50 mg/kg) to induce breast tumor development. Tumor treatment was initiated at an approximate size of 500 mm 3 . Tumors were either administered PLD (100 Ag) once per week for 2 weeks or received no treatment.…”

Section: Model I: Mnu-induced Rat Mammary Tumor Modelmentioning

confidence: 99%

“…administration in neu-N mice. Mice bearing established breast tumors of <125 mm 3 were treated on day 0 by intraductal or i.v. administration of 100 Ag PLD given three times over 3 weeks (Â3, weekly), or were left untreated.…”

Section: Model I: Mnu-induced Rat Mammary Tumor Modelmentioning

confidence: 99%

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Ductal Access for Prevention and Therapy of Mammary Tumors

Murata¹,

Kominsky

Vali³

et al. 2006

Cancer Research

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In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer using the rat N-methyl-NV -nitrosourea-induced and spontaneous HER-2/neu transgenic mouse (neu-N) models of breast cancer. Intraductal administration of PLD to neu-N mice caused regression of established tumors and prevented tumor development more effectively than i.v. injection (P < 0.0001). Intraductal administration resulted in lower circulating levels of PLD compared with i.v. administration, with no evidence of systemic toxicity or long-term histopathologic changes in the mammary gland. Compared with systemic administration, intraductal injection provides direct access to breast lesions with higher local and lower systemic drug exposure. These studies suggest that this approach has potential for application to prevention and neoadjuvant therapy of early breast cancer. (Cancer Res 2006; 66(2): 638-45)

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Section: Model I: Mnu-induced Rat Mammary Tumor Modelmentioning

confidence: 99%

Section: Model I: Mnu-induced Rat Mammary Tumor Modelmentioning

confidence: 99%

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Ductal Access for Prevention and Therapy of Mammary Tumors

Murata¹,

Kominsky

Vali³

et al. 2006

Cancer Research

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“…For example, Okugawa and colleagues showed that rats with N-methyl N'-nitrosourea (MNU)-induced breast tumors exhibited significant reduction in tumor burden and total number of mammary carcinomas when treated with intraductal paclitaxel (27). Similarly, Sukumar and colleagues have shown that intraductal administration of various anticancer drugs, such as pegylated liposomal doxorubicin (PLD), 4-hydroxytamoxifen carboplatin, methotrexate, nanoparticle albuminbound paclitaxel, and 5-fluorouracil was associated with a significant reduction in tumor formation or protected against tumor development in the MNU model, and also minimized the toxic effects of the drugs (28,29).…”

Section: Introductionmentioning

confidence: 99%

A Feasibility Study of the Intraductal Administration of Chemotherapy

Love

Zhang

Gordon

et al. 2013

Cancer Prevention Research

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Preclinical data have shown the potential of the intraductal administration of chemotherapy for breast cancer prevention. Direct translation of this work has been stymied by the anatomical differences between rodents (one duct per teat) and women (5-9 ductal systems per breast). The objective of this phase I study was to show the safety and feasibility of intraductal administration of chemotherapy drugs into multiple ducts within one breast in women awaiting mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in this dose escalation study conducted at a single center in Beijing, China. Under local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated liposomal doxorubicin (PLD), was administered into five to eight ducts at three dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed after a delay. Pathologic analysis showed marked effects on breast duct epithelium in ducts treated with either drug compared with untreated ducts. The study investigators had no difficulty in identifying or cannulating ducts except in one case with a central cancer with subareolar involvement. This study shows the safety and feasibility of intraductal administration of chemotherapy into multiple ducts for the purpose of breast cancer prevention. This is an important step toward implementation of this strategy as a "chemical mastectomy", where the potential for carcinogenesis in the ductal epithelium is eliminated pharmacologically, locally, and without the need for surgery. Cancer Prev Res; 6(1); 51-58. Ó2012 AACR.

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“…For example, results of recent studies have shown that rats with N-methyl N′-nitrosourea-induced breast tumors exhibited significant reduction in tumor formation upon intraductal treatment with various anticancer agents, including paclitaxel, pegylated liposomal doxorubicin (PLD), 4-hydroxytamoxifen, carboplatin, methotrexate, nanoparticle albumin-bound paclitaxel and 5-fluorouracil, with minimal toxic effects. 20–22 Similarly, human epidermal growth factor receptor 2/ neu transgenic mice, which spontaneously develop neu overex-pressing multifocal mammary adenocarcinoma beginning at approximately 4–5 months of age, exhibited higher levels of tumor regression and prevention of tumor development upon intraductal PLD treatment than mice that received intravenous PLD. 21 …”

Section: Introductionmentioning

confidence: 99%

Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

Mahoney

Gordon

Rao

et al. 2013

Clinical Breast Cancer

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Many women with ductal carcinoma in situ (DCIS) are treated with extensive surgery, radiation, and hormone therapy due to the inability to monitor the disease and to determine which cases will progress to invasive cancer. We assessed the safety and feasibility of administering chemotherapy directly into DCIS-containing ducts in 13 women before definitive surgery. The treatment was safe, feasible, and well tolerated, supporting further development of this strategy for management of DCIS. Introduction Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. Patients and Methods Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. Results Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. Conclusions Intraductal therapy offers a nonsurgical strategy to treat DCIS at the site of disease, potentially minimizing the adverse effects of systemic treatment while preventing development of invasive cancer.

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Effect of perductal paclitaxel exposure on the development of MNU-induced mammary carcinoma in female S–D rats

Abstract: Local administration of paclitaxel may be useful for treatment of breast cancer.

Cited by 29 publications

References 20 publications

Ductal Access for Prevention and Therapy of Mammary Tumors

Ductal Access for Prevention and Therapy of Mammary Tumors

A Feasibility Study of the Intraductal Administration of Chemotherapy

Intraductal Therapy of Ductal Carcinoma In Situ: A Presurgery Study

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