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Rapatar, a nanoformulation of rapamycin, decreases chemically-induced benign prostate hyperplasia in rats.

Lesovaya EA, Kirsanov KI, Antoshina EE, Trukhanova LS, Gorkova TG, Shipaeva EV, Salimov RM, Belitsky GA, Blagosklonny MV, Yakubovskaya MG, Chernova OB - Oncotarget (2015)

Bottom Line: Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively.Rapatar normalized weight of the lateral lobes in sulpiride-induced BPH, the most relevant animal model of human BPH.No obvious side effects of Rapatar were detected.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Carcinogenesis, Blokhin Cancer Research Center, Moscow, Russia.

ABSTRACT
Benign prostatic hyperplasia (BPH) is the most common age-related disease in men. Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively. We found that Rapatar prevented hypertrophic and hyperplastic abnormalities and degenerative alterations in both BPH models. Rapatar normalized weight of the lateral lobes in sulpiride-induced BPH, the most relevant animal model of human BPH. Unlike Finasteride, a standard therapy of BPH, Rapatar reduced inflammation caused by sulpiride. No obvious side effects of Rapatar were detected. Our data provide a rationale for clinical trials of Rapatar in patients suffering from BPH.

No MeSH data available.


Related in: MedlinePlus

Histology of ventral (A-D) and lateral prostate (E-H)A.Venstral lobe of intact rats, H&E, x100; B. Testosterone-induced BPH (irregular acinar shape with villous projections of different sizes into the lumen), x80. C. Rapatar normalized GP ventral lobe structure, H&E, x60; D. 30 days of co-administration of Testosterone with Finasteride (glands are partially atrophic, with dilated, angular profiles, adenomatous hyperplasia), H&E, x60. E. Prostatic lateral lobe of intact rats (Control-S), H&E, x60; F. 30 days after Sulpiride treatment (adenomatous hyperplasia manifested by acinar epithelium proliferation, inflammatory infiltration of the stroma), H&E, x60. G. Rapatar normalized LP structure, H&E, x60; H. 30 days of co-administration of Finasteride with Sulpiride (glands are partially atrophic, with dilated, angular profiles,adenomatous hyperplasia, inflammatory infiltration of the stroma), H&E, x60.
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Figure 2: Histology of ventral (A-D) and lateral prostate (E-H)A.Venstral lobe of intact rats, H&E, x100; B. Testosterone-induced BPH (irregular acinar shape with villous projections of different sizes into the lumen), x80. C. Rapatar normalized GP ventral lobe structure, H&E, x60; D. 30 days of co-administration of Testosterone with Finasteride (glands are partially atrophic, with dilated, angular profiles, adenomatous hyperplasia), H&E, x60. E. Prostatic lateral lobe of intact rats (Control-S), H&E, x60; F. 30 days after Sulpiride treatment (adenomatous hyperplasia manifested by acinar epithelium proliferation, inflammatory infiltration of the stroma), H&E, x60. G. Rapatar normalized LP structure, H&E, x60; H. 30 days of co-administration of Finasteride with Sulpiride (glands are partially atrophic, with dilated, angular profiles,adenomatous hyperplasia, inflammatory infiltration of the stroma), H&E, x60.

Mentions: The rat prostate gland has tubuloacinar structure (Figure 2A, 2E). The acini are lined with epithelium and surrounded by loose, fibrous connective tissue containing smooth-muscle fibers and blood vessels. The acini located along the periphery of the lobe are smaller, but their walls are more folded. The epithelial cells of the acinar lining are cylindrical, prismatic or cuboidal with a basal nucleus. The dorsal and lateral lobes are located tightly against each other to the extent that they appear macroscopically as a single lobe. But a very thin connective-tissue septum can be used to distinguish between them microscopically. The acini of the lateral and dorsal lobes are smaller than those of the ventral lobes and have a more pronounced degree of folding (Figure 2A, 2E). As small acini areas are located in the gland section irregularly, the stroma and small acini percentage assessment may depends on the occasional or subjective investigator choice of the sites (Figure 3A). To prevent the bias, we analyzed entire lobe sections scanned in full scale and overlaid with a grid in order to estimate the relative stroma and acini areas (Figure 3B). We did not reveal any change in the relative stroma areas in bothTestosterone-induced (Figure 2A, 2B) and sulpiride-induced BPH (Figure 2E, 2F, Table 2). In both testosterone- and in Sulpiride-induced BPH, adenomatous hyperplasia was manifested by an increased proportion of small acini surrounding large glands (Figure 2B, 2F, Table 2), in agreement with previous results [17]. In sulpiride-induced BPH, proportion of small acini was 40±2.4%, compared with 21±1%, in control. In Testosterone-induced BPH, there was 1.75 fold increase of small acini portion in the ventral lobes: from 21.2±2.9% to 37.2±2.1% (Table 2).


Rapatar, a nanoformulation of rapamycin, decreases chemically-induced benign prostate hyperplasia in rats.

Lesovaya EA, Kirsanov KI, Antoshina EE, Trukhanova LS, Gorkova TG, Shipaeva EV, Salimov RM, Belitsky GA, Blagosklonny MV, Yakubovskaya MG, Chernova OB - Oncotarget (2015)

Histology of ventral (A-D) and lateral prostate (E-H)A.Venstral lobe of intact rats, H&E, x100; B. Testosterone-induced BPH (irregular acinar shape with villous projections of different sizes into the lumen), x80. C. Rapatar normalized GP ventral lobe structure, H&E, x60; D. 30 days of co-administration of Testosterone with Finasteride (glands are partially atrophic, with dilated, angular profiles, adenomatous hyperplasia), H&E, x60. E. Prostatic lateral lobe of intact rats (Control-S), H&E, x60; F. 30 days after Sulpiride treatment (adenomatous hyperplasia manifested by acinar epithelium proliferation, inflammatory infiltration of the stroma), H&E, x60. G. Rapatar normalized LP structure, H&E, x60; H. 30 days of co-administration of Finasteride with Sulpiride (glands are partially atrophic, with dilated, angular profiles,adenomatous hyperplasia, inflammatory infiltration of the stroma), H&E, x60.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496392&req=5

Figure 2: Histology of ventral (A-D) and lateral prostate (E-H)A.Venstral lobe of intact rats, H&E, x100; B. Testosterone-induced BPH (irregular acinar shape with villous projections of different sizes into the lumen), x80. C. Rapatar normalized GP ventral lobe structure, H&E, x60; D. 30 days of co-administration of Testosterone with Finasteride (glands are partially atrophic, with dilated, angular profiles, adenomatous hyperplasia), H&E, x60. E. Prostatic lateral lobe of intact rats (Control-S), H&E, x60; F. 30 days after Sulpiride treatment (adenomatous hyperplasia manifested by acinar epithelium proliferation, inflammatory infiltration of the stroma), H&E, x60. G. Rapatar normalized LP structure, H&E, x60; H. 30 days of co-administration of Finasteride with Sulpiride (glands are partially atrophic, with dilated, angular profiles,adenomatous hyperplasia, inflammatory infiltration of the stroma), H&E, x60.
Mentions: The rat prostate gland has tubuloacinar structure (Figure 2A, 2E). The acini are lined with epithelium and surrounded by loose, fibrous connective tissue containing smooth-muscle fibers and blood vessels. The acini located along the periphery of the lobe are smaller, but their walls are more folded. The epithelial cells of the acinar lining are cylindrical, prismatic or cuboidal with a basal nucleus. The dorsal and lateral lobes are located tightly against each other to the extent that they appear macroscopically as a single lobe. But a very thin connective-tissue septum can be used to distinguish between them microscopically. The acini of the lateral and dorsal lobes are smaller than those of the ventral lobes and have a more pronounced degree of folding (Figure 2A, 2E). As small acini areas are located in the gland section irregularly, the stroma and small acini percentage assessment may depends on the occasional or subjective investigator choice of the sites (Figure 3A). To prevent the bias, we analyzed entire lobe sections scanned in full scale and overlaid with a grid in order to estimate the relative stroma and acini areas (Figure 3B). We did not reveal any change in the relative stroma areas in bothTestosterone-induced (Figure 2A, 2B) and sulpiride-induced BPH (Figure 2E, 2F, Table 2). In both testosterone- and in Sulpiride-induced BPH, adenomatous hyperplasia was manifested by an increased proportion of small acini surrounding large glands (Figure 2B, 2F, Table 2), in agreement with previous results [17]. In sulpiride-induced BPH, proportion of small acini was 40±2.4%, compared with 21±1%, in control. In Testosterone-induced BPH, there was 1.75 fold increase of small acini portion in the ventral lobes: from 21.2±2.9% to 37.2±2.1% (Table 2).

Bottom Line: Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively.Rapatar normalized weight of the lateral lobes in sulpiride-induced BPH, the most relevant animal model of human BPH.No obvious side effects of Rapatar were detected.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Carcinogenesis, Blokhin Cancer Research Center, Moscow, Russia.

ABSTRACT
Benign prostatic hyperplasia (BPH) is the most common age-related disease in men. Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively. We found that Rapatar prevented hypertrophic and hyperplastic abnormalities and degenerative alterations in both BPH models. Rapatar normalized weight of the lateral lobes in sulpiride-induced BPH, the most relevant animal model of human BPH. Unlike Finasteride, a standard therapy of BPH, Rapatar reduced inflammation caused by sulpiride. No obvious side effects of Rapatar were detected. Our data provide a rationale for clinical trials of Rapatar in patients suffering from BPH.

No MeSH data available.


Related in: MedlinePlus