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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

Noninvasive monitoring of treatment responses in breast cancer tumors. Photographs illustrate typical changes in individual mice; BLI signal superimposed upon white light image. (A) Control mouse that received neither Vit D treatment nor ALA-PDT; (B) mouse that received only ALA-PDT; (C) mouse that received both Vit D treatment for 3 days followed by ALA-PDT on fourth day. Graphs quantify relative change in radiance (photons sec−1 cm−2 sr−1). Mean ± SEM; number of tumors per treatment group in parenthesis. P values from paired two-sided t-tests. NS, not significant; BLI, bioluminescence imaging; ALA, 5-aminolevulinate; PDT, photodynamic therapy.
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fig03: Noninvasive monitoring of treatment responses in breast cancer tumors. Photographs illustrate typical changes in individual mice; BLI signal superimposed upon white light image. (A) Control mouse that received neither Vit D treatment nor ALA-PDT; (B) mouse that received only ALA-PDT; (C) mouse that received both Vit D treatment for 3 days followed by ALA-PDT on fourth day. Graphs quantify relative change in radiance (photons sec−1 cm−2 sr−1). Mean ± SEM; number of tumors per treatment group in parenthesis. P values from paired two-sided t-tests. NS, not significant; BLI, bioluminescence imaging; ALA, 5-aminolevulinate; PDT, photodynamic therapy.

Mentions: Figure3 shows representative examples of the BLI signal from orthotopic breast tumors in-vivo at three different times in various experimental groups, before and after PDT. The bioluminescence signal, displayed as a pseudocolored scale, corresponds to the radiance (photons sec−1 cm−2 sr−1) emitted from each tumor due to the reaction between luciferin substrate and luciferase enzyme. In the first group of mice which received no agents (Fig.3A), radiance continued to increase from day 4 to day 8, consistent with continuous/unrestricted growth of luciferase-bearing cancer cells in the breast fat pad environment. In the second group of mice, the increase in radiance between day 7 and day 8 was reversed by application of ALA-PDT at day 7, resulting in a 45% drop in signal (Fig.3B). However, radiance from these tumors at day 8 was still higher than at day 4, indicating room for improvement in the treatment protocol. In contrast, all animals that received Vit D/ALA-PDT treatment showed a statistically significant reduction (82 ± 6%, P < 0.001) in radiance at day 8, suggesting that viable tumor cells had decreased to one-fifth of the number before PDT (Fig.3C). (To confirm that the decrease in luminescence after VitD/ALA-PDT actually corresponded to changes in the number of living cells after treatment, tumors were histologically examined after biopsy; see below).


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

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

Noninvasive monitoring of treatment responses in breast cancer tumors. Photographs illustrate typical changes in individual mice; BLI signal superimposed upon white light image. (A) Control mouse that received neither Vit D treatment nor ALA-PDT; (B) mouse that received only ALA-PDT; (C) mouse that received both Vit D treatment for 3 days followed by ALA-PDT on fourth day. Graphs quantify relative change in radiance (photons sec−1 cm−2 sr−1). Mean ± SEM; number of tumors per treatment group in parenthesis. P values from paired two-sided t-tests. NS, not significant; BLI, bioluminescence imaging; ALA, 5-aminolevulinate; PDT, photodynamic therapy.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig03: Noninvasive monitoring of treatment responses in breast cancer tumors. Photographs illustrate typical changes in individual mice; BLI signal superimposed upon white light image. (A) Control mouse that received neither Vit D treatment nor ALA-PDT; (B) mouse that received only ALA-PDT; (C) mouse that received both Vit D treatment for 3 days followed by ALA-PDT on fourth day. Graphs quantify relative change in radiance (photons sec−1 cm−2 sr−1). Mean ± SEM; number of tumors per treatment group in parenthesis. P values from paired two-sided t-tests. NS, not significant; BLI, bioluminescence imaging; ALA, 5-aminolevulinate; PDT, photodynamic therapy.
Mentions: Figure3 shows representative examples of the BLI signal from orthotopic breast tumors in-vivo at three different times in various experimental groups, before and after PDT. The bioluminescence signal, displayed as a pseudocolored scale, corresponds to the radiance (photons sec−1 cm−2 sr−1) emitted from each tumor due to the reaction between luciferin substrate and luciferase enzyme. In the first group of mice which received no agents (Fig.3A), radiance continued to increase from day 4 to day 8, consistent with continuous/unrestricted growth of luciferase-bearing cancer cells in the breast fat pad environment. In the second group of mice, the increase in radiance between day 7 and day 8 was reversed by application of ALA-PDT at day 7, resulting in a 45% drop in signal (Fig.3B). However, radiance from these tumors at day 8 was still higher than at day 4, indicating room for improvement in the treatment protocol. In contrast, all animals that received Vit D/ALA-PDT treatment showed a statistically significant reduction (82 ± 6%, P < 0.001) in radiance at day 8, suggesting that viable tumor cells had decreased to one-fifth of the number before PDT (Fig.3C). (To confirm that the decrease in luminescence after VitD/ALA-PDT actually corresponded to changes in the number of living cells after treatment, tumors were histologically examined after biopsy; see below).

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