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Chemoprevention of breast cancer with tamoxifen: recent experience and future perspectives
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
B. Bonanni, A. Guerrieri-Gonzaga, N. Rotmensz, A. Decensi
Since tamoxifen has a very high tissue/serum concentration ratio34,35, the tissue level attainable with 10 mg every other day exceeds the growth-inhibitory concentration of tamoxifen and N-desmethyltamoxifen in breast cancer cell lines, which is approximately 35 ng/ml36–38. In addition, the concomitant activity of metabolite X, which has a significant growth-inhibitory activity in breast cancer cell lines, may further contribute to the total drug inhibitory activity. Moreover, in vivo studies in a spontaneous rat mammary tumor model showed that a dose equivalent to 1 mg/day in humans leads to a 94% inhibition of mammary tumor formation compared with control animals39. Interestingly, a recent cross-sectional study conducted in older nursing home residents has shown a significant reduction of bone fracture rate among women with breast cancer taking 10 mg/day tamoxifen. During the first 1.5-year period for which bone fractures were documented, the fracture rates were 7.6% in 5196 untreated control women, 3.2% in the 125 women receiving 10 mg/day tamoxifen, and 6.7% in the 1248 women receiving 20 mg/day tamoxifen. The odds ratio for 20 mg/day compared with controls is 0.92 (95% CI 0.72–1.16), while the odds ratio for 10 mg/day compared with controls is 0.31 (95% CI 0.11–0.87, p = 0.025)40. Altogether, these findings provide a strong rationale for a lower dose of tamoxifen in a preventive context (Table 1).
In Vivo Observations of Tumor Blood Flow
Published in Hans-Inge Peterson, Tumor Blood Circulation: Angiogenesis, Vascular Morphology and Blood Flow of Experimental and Human Tumors, 2020
If one wants to investigate some of the complex permeability functions of the microvascular system, the use of a dye that binds to macromolecules is indicated. Evans blue is such a dye, and it has been used to examine radiation-induced increased vascular permeability in frozen sections.26 However, for investigations with serial angiography, nonbinding dyes which can be used in high concentrations are indicated. An example of a serial microangiogram in a mammary tumor in the mouse is presented in Figure 5. The tumor is the same as the one depicted in Figure 4, and it is, therefore, possible to compare the characteristics of the microcirculatory flow with the angioarchitecture. The dye used in this instance is the water-soluble, nontoxic dye “pyranin” which can be injected i.v. with a solution concentration as high as 10%.
Prolactin and Murine Models for Human Breast Cancer
Published in Nagasawa Hiroshi, Prolactin and Lesions in Breast, Uterus, and Prostate, 2020
Hiroshi Nagasawa, Clifford W. Welsh
While mammary tumors develop spontaneously in rats, there are striking differences in mammary tumorigenic potential between rat strains. In female Sprague-Dawley rats, the incidence of mammary tumors is often 70% at 2 to 3 years of age. In female Long-Evans rats of similar age, mammary tumor incidence is less than 40%. Female Wistar rats have a high incidence of mammary tumors.
PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research
Published in International Journal of Hyperthermia, 2023
Ze-Peng Yu, Xing-Wei Sun, Ya-Ping He, Jun Gu, Yong Jin
To assess the antitumor immune response of distant tumors outside the ablation zone after Cryo treatment, we inoculated murine-derived 4T1 BC cell suspensions into the mammary fat pads of Balb/C mice bilaterally. When the tumor length diameter reached approximately 0.8 cm, Cryo was performed on the right mammary tumor, preserving the left side and observing its malignant growth trend (Figure 1(A)). The H&E staining results indicated that the bilateral mammary tumor model was successfully constructed (Figure 1(B)). The left tumor became slightly smaller in size on Day 3 after treatment (Figure 1(C)). However, after a short period of growth inhibition, the left tumor gradually resumed its malignant growth rate at Days 6–12 (Figure 1(C)), suggesting that these two time points may reflect the different immune response states of tumor-infiltrating lymphocytes (TILs) in the tumor tissue.
Tumor aggressiveness is independent of radiation quality in murine hepatocellular carcinoma and mammary tumor models
Published in International Journal of Radiation Biology, 2021
Eshwar B. Udho, Shane M. Huebner, Dawn M. Albrecht, Kristina A. Matkowskyj, Linda Clipson, Catigan A. Hedican, Rachel Koth, Santina M. Snow, Emily L. Eberhardt, Devon Miller, Rachel Van Doorn, Genti Gjyzeli, Erin K. Spengler, Douglas R. Storts, Douglas H. Thamm, Elijah F. Edmondson, Michael M. Weil, Richard B. Halberg, Jeffery W. Bacher
FVB/N-Tg(MMTV-PyMT) transgenic mice express the Polyoma Virus middle T antigen under the control of the mouse mammary tumor virus promoter/enhancer. These mice have a high penetrance of early onset of mammary cancer compared to other mammary tumor models and females develop palpable mammary tumors which metastasize to the lung. A breeding colony of FVB/N-Tg(MMTV-PyMT) was established at CSU and male mice from this colony were mated with female FVB/N or DBA/2 mice to generate female mice that spontaneously develop mammary tumors with a high (FVB) or low (DBAxFVB)F1 propensity to metastasize (Lifsted et al. 1998). A total of 44 female mice comprising 24 FVB and 20 (DBAxFVB)F1 were shipped to BNL and exposed to either 0.2 Gy of 300 MeV 28Si ions or sham-irradiated at 33–37 days of age and then shipped back to Colorado State University. Each mouse was palpated twice weekly until a mammary tumor was putatively detected. One week later, the presence of the tumor was confirmed by palpation and the mouse was then monitored for an additional 40 days or until the tumor reached a maximal diameter of 20 mm or became ulcerated or the mouse developed signs of morbidity requiring euthanasia.
A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice
Published in OncoImmunology, 2019
Sarah Lévesque, Julie Le Naour, Federico Pietrocola, Juliette Paillet, Margerie Kremer, Francesca Castoldi, Elisa E. Baracco, Yan Wang, Erika Vacchelli, Gautier Stoll, Ariane Jolly, Pierre De La Grange, Laurence Zitvogel, Guido Kroemer, Jonathan G. Pol
Hormone- and carcinogen-induced mammary tumor model. Mammary tumors were induced in young (7-week-old) female BALB/c mice by implantation of medroxyprogesterone acetate (MPA)-releasing pellets followed by gavage with the DNA damaging agent 7,12-dimethylbenz[a]anthracene (DMBA) for the following 6 weeks. The overall scheme of tumor induction is illustrated in Figure 1(a). Implanted fibrosarcoma tumor model. 0,3 x 106 MCA205 cells were resuspended in 100 µL of PBS and subcutaneously (s.c.) injected in the right flank of mice under anesthesia with 2.5% isoflurane. Tumor growth was monitored via repeated measurements of the tumor size using a digital caliper. The area of mammary tumors was calculated as follows: tumor size (mm2) = length x width. The volume of fibrosarcoma tumors was calculated using the following formula: tumor size (mm3) = (length x width x height)/8 x 4/3 x π. Mean tumor growth curves were calculated by carrying over the last tumor size values of the mice that reached endpoint and interrupted when more than 50% of the group had reached endpoint. Mouse survival was carefully monitored. Tumor size exceeding 250 mm2 or 2000 mm3, tumor ulceration, weight loss superior to 20% as compared to the beginning of the treatment and poor body condition were considered as endpoints.