scholarly journals The effect of lipid derivative of anti-tumor drug sarcolysin embedded in phospholipid nanoparticles in the experiments in vivo

2021 ◽  
Vol 67 (6) ◽  
pp. 491-499
Author(s):  
Yu.A. Tereshkina ◽  
T.I. Torkhovskaya ◽  
M.A. Sanzhakov ◽  
L.V. Kostryukova ◽  
Yu.Yu. Khudoklinova ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Antitumor Agent ◽  
Mouse Mammary Gland ◽  
Lymphocytic Leukemia ◽  
Pharmacokinetic Parameters ◽  
Tumor Growth Inhibition ◽  
Phospholipid Nanoparticles ◽  
Lipid Derivative ◽  
Ld50 Value

To improve the therapeutic properties of the antitumor agent Sarcolysin, we have previously developed and characterized a dosage form representing its ester conjugate with decanol embedded in ultra-small phospholipid nanoparticles less than 30 nm in size (“Sarcolysin-NP”). The effect of the resulting composition was investigated in vivo in comparison with the free substance of sarcolysin. The composition intravenous administration to mice showed an improvement in the pharmacokinetic parameters of sarcolysin associated with its initial higher (by 22%) level in the blood and prolonged circulation, which was also observed in mice with P388 tumor. In mice with three types of tumors — lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma of the mammary gland Ca755 — administration of two doses of sarcolysin over a period of 7 days showed its predominant antitumor effect. The maximum tumor growth inhibition was noted for lymphocytic leukemia L1210 and adenocarcinoma of the mouse mammary gland Ca755 (at a dose of Sarcolysin-NP — 8,4 mg/kg), which was higher in comparison with free substance by more than 24% and 17%, respectively. Differences in the life span of the treated animals were revealed significantly at a dose of 10 mg/kg and amounted to 25% and 17,4% for lymphocytic leukemia P388 and L1210, respectively, and 11% for adenocarcinoma Ca755. In an experiment on rats, acute toxicity of Sarcolysin-NP administered intravenously showed that an average LD50 value 2-3 times exceeded a similar parameter for commercial preparations of free sarcolysin (Melphalan and Alkeran), which indicates its lower toxicity.

scholarly journals In vivo MRI of early stage mammary cancers and the normal mouse mammary gland

2011 ◽  
Vol 24 (7) ◽  
pp. 880-887 ◽  
Author(s):  
Sanaz A. Jansen ◽  
Suzanne D. Conzen ◽  
Xiaobing Fan ◽  
Erica Markiewicz ◽  
Thomas Krausz ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Normal Mouse ◽  
Early Stage ◽  
Mouse Mammary Gland

RAPIDLY-LABELLED RNA IN THE MOUSE MAMMARY GLAND BEFORE AND DURING LACTATION

1973 ◽  
Vol 56 (1) ◽  
pp. 145-152 ◽  
Author(s):  
D. N. BANERJEE ◽  
M. R. BANERJEE
Keyword(s):  
Mammary Gland ◽  
Ribosomal Rna ◽  
Gradient Analysis ◽  
Sucrose Density Gradient ◽  
Mouse Mammary Gland ◽  
Nuclear Fraction ◽  
Cytoplasmic Rna ◽  
Nuclear Rna ◽  
Nuclear Synthesis

SUMMARY Linear sucrose density gradient analysis showed that the synthesis of rapidly-labelled high molecular weight RNA was virtually absent in the mammary glands of virgin mice. The rapidly-labelled RNA was first evident in the mammary gland in pregnancy and was also present during lactation. The bulk of this newly-made nuclear RNA sedimented as 45S and 32S fractions after a 15-min [3H]uridine pulse period in vivo. No labelled 18S RNA was detectable in the nuclear fraction after the 15-min pulse but it was present in the cytoplasm, suggesting that the 18S RNA migrates to the cytoplasm almost immediately after its formation. Thirty minutes after injection of [3H]uridine, the initial radioactivity of the 45S region migrated to the 32S fraction and a labelled 28S peak was also present in the cytoplasmic RNA at 60 min, suggesting that the processed 28S ribosomal RNA in the mammary gland began to migrate to the cytoplasm between 30 and 60 min after the nuclear synthesis of the precursor molecule.

Electrical potentials and cell-to-cell dye movement in mouse mammary gland during lactation

1984 ◽  
Vol 247 (1) ◽  
pp. C20-C25 ◽  
Author(s):  
S. E. Berga
Keyword(s):  
Mammary Gland ◽  
Lucifer Yellow ◽  
Mammary Epithelium ◽  
Mouse Mammary Gland ◽  
Dye Transfer ◽  
Alveolar Cells ◽  
Electrical Potentials ◽  
Lucifer Yellow Ch ◽  
Electrophysiological Studies

Stable potentials were recorded with microelectrodes in an in vivo preparation of the mammary gland from the anesthetized lactating mouse. Location of the microelectrode tip was determined by ionophoretic injection of the fluorescent dye Lucifer yellow CH. Fifteen dye injections were localized to mammary alveolar cells; the average recorded potential for these penetrations was -49 +/- 2 mV. Cell-to-cell dye transfer between alveolar cells was observed with all intracellular Lucifer yellow injections. Ten dye injections were localized to the alveolar lumina with an average recorded potential of -35 +/- 2 mV. With these penetrations Lucifer yellow spread rapidly to many alveolar lumina. These findings indicate that stable potentials can be obtained from both cells and lumina in the in vivo mammary gland, demonstrating the feasibility of electrophysiological studies of the mammary epithelium. The presence of a large transepithelial potential provides evidence for physiologically tight junctions between mammary alveolar cells. In addition, the distribution of Lucifer yellow shows that mammary alveolar cells are coupled and suggests that milk flows freely between alveolar lumina.

HORMONAL REGULATION OF RNA AND PROTEIN SYNTHESIS IN THE MOUSE MAMMARY GLAND BEFORE AND DURING LACTATION

1971 ◽  
Vol 50 (2) ◽  
pp. 281-291 ◽  
Author(s):  
M. R. BANERJEE ◽  
FERNE M. ROGERS ◽  
D. N. BANERJEE
Keyword(s):  
Protein Synthesis ◽  
Mammary Gland ◽  
Hormonal Regulation ◽  
Rna Synthesis ◽  
Mouse Mammary Gland ◽  
Synthetic Activity ◽  
Tissue Homogenate ◽  
Mammary Tissue ◽  
Leucine Incorporation

SUMMARY As measured by [3H]uridine incorporation in vivo, the low rate of RNA synthesis in the mammary gland of virgin C3H and BALB/c mice increased sixfold in the mammary tissue of 15-day pregnant mice. In the 5-day lactating gland, RNA synthesis was ten times higher than that in virgin mammary tissue. On the 10th day of lactation this increased RNA synthetic activity in the mammary gland was considerably reduced but was still twice that of the mammary tissue of virgin mice. Twenty-four hours after adrenalectomy, RNA synthesis in lactating glands was reduced by over 80%, whereas in the mammary gland before lactation, it was reduced by 20–30% only. A single i.p. injection of 250 μg of cortisol led to a threefold increase of RNA synthesis within 1 to 2 h in lactating glands of adrenalectomized mice; this was followed by a decline. Incorporation of [3H]leucine into trichloroacetic acid-insoluble material from lactating mammary tissue was used as a measure of'total protein' synthesis, and [3H]leucine radioactivity determined in Ca2+−rennin precipitate of 105000 g supernatant of lactating mammary tissue homogenate was used as a measure of casein synthesis. Adrenalectomy caused a 50% reduction of 'total protein' synthesis, whereas synthesis of 'casein-like' phosphoprotein virtually stopped after the operation. The injection of cortisol into adrenalectomized mice induced a selective increase of [3H]leucine incorporation into the casein of lactating glands. The results indicate that RNA synthesis in the mammary tissue is more dependent on adrenal hormones during the functional than the structural state of differentiation. The hormonal regulation of RNA synthesis and its role in milk protein synthesis in the mammary gland in vivo is discussed.

scholarly journals Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma

2002 ◽  
Vol 156 (1) ◽  
pp. 185-198 ◽  
Author(s):  
Zhe Jiang ◽  
Eldad Zacksenhaus
Keyword(s):  
Cell Proliferation ◽  
Mammary Gland ◽  
Cellular Proliferation ◽  
Mammary Epithelium ◽  
Specific Effect ◽  
Mouse Mammary Gland ◽  
Transient Activation ◽  
Proliferation And Apoptosis

The retinoblastoma (Rb) tumor suppressor controls cellular proliferation, survival, and differentiation and is functionally inactivated by mutations or hyperphosphorylation in most human cancers. Although activation of endogenous Rb is thought to provide an effective approach to suppress cell proliferation, long-term inhibition of apoptosis by active Rb may have detrimental consequences in vivo. To directly test these paradigms, we targeted phosphorylation-resistant constitutively active Rb alleles, RbΔKs, to the mouse mammary gland. Pubescent transgenic females displayed reduced ductal elongation and cell proliferation at the endbuds. Postpuberty transgenic mice exhibited precocious cellular differentiation and β-casein expression and extended survival of the mammary epithelium with a moderate but specific effect on the expression of E2F1, IGF1Rα, and phospho–protein kinase B/AKT. Remarkably, ∼30% RbΔK transgenic females developed focal hyperplastic nodules, and ∼7% exhibited full-blown mammary adenocarcinomas within 15 mo. Expression of the RbΔK transgene in these mammary tumors was reduced greatly. Our results suggest that transient activation of Rb induces cancer by extending cell survival and that the dual effects of Rb on cell proliferation and apoptosis impose an inherent caveat to the use of the Rb pathway for long-term cancer therapy.

scholarly journals Differential Hormonal Regulation and Function of Progesterone Receptor Isoforms in Normal Adult Mouse Mammary Gland

Endocrinology ◽  
2007 ◽  
Vol 148 (5) ◽  
pp. 2290-2300 ◽  
Author(s):  
Mark D. Aupperlee ◽  
Sandra Z. Haslam
Keyword(s):  
Mammary Gland ◽  
Hormonal Regulation ◽  
Adult Mouse ◽  
Mouse Mammary Gland ◽  
Functional Roles ◽  
Progesterone Receptor Isoforms ◽  
Receptor Isoforms ◽  
Mitogenic Action ◽  
And Function

In normal mouse mammary gland, the mitogenic action of progesterone (P) is mediated by two P receptor (PR) isoforms, PRA and PRB. PRA is predominantly expressed in the adult virgin, and PRB is predominantly expressed during pregnancy. To investigate hormonal regulation of PR isoform expression and isoform-specific functions in vivo, adult ovariectomized BALB/c mice were treated for 3, 5, or 10 d with estrogen (E), P, or estrogen plus progesterone (E+P). Using an immunohistochemical approach with isoform-specific antibodies, we investigated hormonal regulation of PRA and PRB and their functional roles in proliferation and morphogenesis. Significant E-induced proliferation was only observed after 5 d at the distal tips of ducts; there was no sidebranching or alveologenesis. P induced proliferation that resulted in sidebranching and alveologenesis, but E+P treatment produced more proliferation sooner and more extensive sidebranching and alveologenesis. PRA levels were increased by E and decreased by P. Increased PRB levels were induced by treatment with P or E+P and coincided with the formation of alveoli. PRA was the predominant PR isoform expressed during sidebranching, and colocalization of PRA with 5-bromo-2′-deoxyuridine revealed that proliferation of PRA-positive and -negative cells was responsible for P-induced sidebranching. PRB was the predominant PR isoform expressed during alveologenesis, and colocalization of PRB with 5-bromo-2′-deoxyuridine showed that both PRB-positive and -negative cells proliferated during alveolar expansion. These results demonstrate different hormonal regulation of PRA and PRB levels in vivo and suggest that P can induce proliferation through either PRA or PRB via direct and paracrine mechanisms.

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