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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

Vit D pretreated breast cancer shows enhanced tumor-specific cell death after ALA-PDT. (A) Examples of TUNEL-labeled apoptotic nuclei in tumors from control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (B) Quantification of cell death in tumors, treated as in (A). (C) Cell death in normal skin adjacent to the tumors in control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (D) Quantification of cell death in the normal epidermis shows no significant differences. Dotted line, junction between stratum corneum (above) and viable epidermis. Dashed line, basement membrane between dermis and epidermis. Data points represent mean ± SEM; P values from unpaired two-sided t-tests; numerals in parenthesis indicate number of tumors (three histologic sections per tumor) for each treatment condition. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.
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fig05: Vit D pretreated breast cancer shows enhanced tumor-specific cell death after ALA-PDT. (A) Examples of TUNEL-labeled apoptotic nuclei in tumors from control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (B) Quantification of cell death in tumors, treated as in (A). (C) Cell death in normal skin adjacent to the tumors in control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (D) Quantification of cell death in the normal epidermis shows no significant differences. Dotted line, junction between stratum corneum (above) and viable epidermis. Dashed line, basement membrane between dermis and epidermis. Data points represent mean ± SEM; P values from unpaired two-sided t-tests; numerals in parenthesis indicate number of tumors (three histologic sections per tumor) for each treatment condition. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.

Mentions: To assess cell-death responses after treatment, a TUNEL assay was performed on formalin-fixed/paraffin-embedded tissues (Fig.5). Results indicated a greater amount of cell death in the MDA-MB-231-luc tumors preconditioned with Vit D prior to ALA-PDT, relative to ALA-PDT alone. Very few TUNEL-positive cells were observed in absolute control tumors (Fig.5A, top). After ALA-PDT, only scattered cell death was seen, limited to the peripheral region of the tumors (Fig.5A, middle). In contrast, widespread cell death was observed throughout tumors that were pretreated with Vit D prior to ALA-PDT (Fig.5A, lower). Quantitative TUNEL results indicated a 4.0 ± 0.7-fold increase in apoptotic cells after ALA-PDT alone, versus a 36.8 ± 7.4-fold increase in tumor cell death after combined treatment (Fig.5B), a highly significant difference.


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

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

Vit D pretreated breast cancer shows enhanced tumor-specific cell death after ALA-PDT. (A) Examples of TUNEL-labeled apoptotic nuclei in tumors from control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (B) Quantification of cell death in tumors, treated as in (A). (C) Cell death in normal skin adjacent to the tumors in control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (D) Quantification of cell death in the normal epidermis shows no significant differences. Dotted line, junction between stratum corneum (above) and viable epidermis. Dashed line, basement membrane between dermis and epidermis. Data points represent mean ± SEM; P values from unpaired two-sided t-tests; numerals in parenthesis indicate number of tumors (three histologic sections per tumor) for each treatment condition. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.
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fig05: Vit D pretreated breast cancer shows enhanced tumor-specific cell death after ALA-PDT. (A) Examples of TUNEL-labeled apoptotic nuclei in tumors from control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (B) Quantification of cell death in tumors, treated as in (A). (C) Cell death in normal skin adjacent to the tumors in control (top), vehicle-PDT (middle), and Vit D-PDT (lower) groups. (D) Quantification of cell death in the normal epidermis shows no significant differences. Dotted line, junction between stratum corneum (above) and viable epidermis. Dashed line, basement membrane between dermis and epidermis. Data points represent mean ± SEM; P values from unpaired two-sided t-tests; numerals in parenthesis indicate number of tumors (three histologic sections per tumor) for each treatment condition. Scale bars, 50 μm. ALA, 5-aminolevulinate; PDT, photodynamic therapy.
Mentions: To assess cell-death responses after treatment, a TUNEL assay was performed on formalin-fixed/paraffin-embedded tissues (Fig.5). Results indicated a greater amount of cell death in the MDA-MB-231-luc tumors preconditioned with Vit D prior to ALA-PDT, relative to ALA-PDT alone. Very few TUNEL-positive cells were observed in absolute control tumors (Fig.5A, top). After ALA-PDT, only scattered cell death was seen, limited to the peripheral region of the tumors (Fig.5A, middle). In contrast, widespread cell death was observed throughout tumors that were pretreated with Vit D prior to ALA-PDT (Fig.5A, lower). Quantitative TUNEL results indicated a 4.0 ± 0.7-fold increase in apoptotic cells after ALA-PDT alone, versus a 36.8 ± 7.4-fold increase in tumor cell death after combined treatment (Fig.5B), a highly significant difference.

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