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Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer.

Rollakanti KR, Anand S, Maytin EV - Cancer Med (2015)

Bottom Line: Cutaneous metastasis occurs more frequently in breast cancer than in any other malignancy in women, causing significant morbidity.Bioluminescence imaging in vivo and immunohistochemical staining confirmed that tumor-specific cell death after ALA-PDT was markedly enhanced (36.8 ± 7.4-fold increase in TUNEL-positive nuclei; radiance decreased to 14% of control) in Vit D pretreated tumors as compared to vehicle-pretreated tumors.The observed enhancement of tumor responses to ALA-PDT after low, nontoxic doses of Vit D supports a new combination approach that deserves consideration in the clinical setting, and offers potential for improved remission of cutaneous breast cancer metastases.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biomedical Engineering, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio, 44115.

No MeSH data available.


Related in: MedlinePlus

Morphological differences in tumors subjected to various treatment conditions. (A–D), These images illustrate the progressive loss of nucleated cells, the increase in colloid-filled cystic spaces (pink), and the increase in completely empty spaces (white), occuring with the addition of Vit D to the ALA-PDT treatment regimen. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.
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fig06: Morphological differences in tumors subjected to various treatment conditions. (A–D), These images illustrate the progressive loss of nucleated cells, the increase in colloid-filled cystic spaces (pink), and the increase in completely empty spaces (white), occuring with the addition of Vit D to the ALA-PDT treatment regimen. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.

Mentions: Figure6 shows representative images of H&E stained sections of paraffin-fixed tumors from four different treatment groups. Untreated controls (Fig.6A) were characterized by the presence of healthy cells arranged in lobular or ductal patterns, which filled the entire microscopic field. In tumors treated with ALA-PDT alone (Fig.6B), and to some extent with Vit D alone (Fig.6C), loss of nucleated cells was observed. However, tumors that received Vit D/ALA-PDT (Fig.6D) showed a dramatic decrease in the density of nucleated cells as compared to control tumors (Fig.7A). In addition, a greater fraction (60–70%) of the tumor area was occupied by eosinophilic material, most likely colloidal casein or other proteins (Fig.7B) or empty spaces completely devoid of any material (Fig.7C). As an additional measure of dying cells, pixel-by-pixel size analysis of nuclei was performed, revealing the highest number of shrunken (pyknotic) or fragmented nuclei in the Vit D-ALA-PDT group (Fig.8). To create a semiquantitative index (damage severity index, DSI) that incorporates all these features and correlates with PDT-induced damage, parameters from Fig.7 were combined with the nuclear size analysis (Fig.8), and the sum of all parameters used as a histologic index (Table1). Values of this index were four-fold higher after Vit D plus ALA-PDT than after ALA-PDT alone, further corroborating the results obtained from bioluminescence (Fig.3) and TUNEL (Fig.5A).


Vitamin D enhances the efficacy of photodynamic therapy in a murine model of breast cancer.

Rollakanti KR, Anand S, Maytin EV - Cancer Med (2015)

Morphological differences in tumors subjected to various treatment conditions. (A–D), These images illustrate the progressive loss of nucleated cells, the increase in colloid-filled cystic spaces (pink), and the increase in completely empty spaces (white), occuring with the addition of Vit D to the ALA-PDT treatment regimen. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4430256&req=5

fig06: Morphological differences in tumors subjected to various treatment conditions. (A–D), These images illustrate the progressive loss of nucleated cells, the increase in colloid-filled cystic spaces (pink), and the increase in completely empty spaces (white), occuring with the addition of Vit D to the ALA-PDT treatment regimen. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.
Mentions: Figure6 shows representative images of H&E stained sections of paraffin-fixed tumors from four different treatment groups. Untreated controls (Fig.6A) were characterized by the presence of healthy cells arranged in lobular or ductal patterns, which filled the entire microscopic field. In tumors treated with ALA-PDT alone (Fig.6B), and to some extent with Vit D alone (Fig.6C), loss of nucleated cells was observed. However, tumors that received Vit D/ALA-PDT (Fig.6D) showed a dramatic decrease in the density of nucleated cells as compared to control tumors (Fig.7A). In addition, a greater fraction (60–70%) of the tumor area was occupied by eosinophilic material, most likely colloidal casein or other proteins (Fig.7B) or empty spaces completely devoid of any material (Fig.7C). As an additional measure of dying cells, pixel-by-pixel size analysis of nuclei was performed, revealing the highest number of shrunken (pyknotic) or fragmented nuclei in the Vit D-ALA-PDT group (Fig.8). To create a semiquantitative index (damage severity index, DSI) that incorporates all these features and correlates with PDT-induced damage, parameters from Fig.7 were combined with the nuclear size analysis (Fig.8), and the sum of all parameters used as a histologic index (Table1). Values of this index were four-fold higher after Vit D plus ALA-PDT than after ALA-PDT alone, further corroborating the results obtained from bioluminescence (Fig.3) and TUNEL (Fig.5A).

Bottom Line: Cutaneous metastasis occurs more frequently in breast cancer than in any other malignancy in women, causing significant morbidity.Bioluminescence imaging in vivo and immunohistochemical staining confirmed that tumor-specific cell death after ALA-PDT was markedly enhanced (36.8 ± 7.4-fold increase in TUNEL-positive nuclei; radiance decreased to 14% of control) in Vit D pretreated tumors as compared to vehicle-pretreated tumors.The observed enhancement of tumor responses to ALA-PDT after low, nontoxic doses of Vit D supports a new combination approach that deserves consideration in the clinical setting, and offers potential for improved remission of cutaneous breast cancer metastases.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical and Biomedical Engineering, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio, 44115.

No MeSH data available.


Related in: MedlinePlus