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Antitumor effect of fibrin glue containing temozolomide against malignant glioma.

Anai S, Hide T, Takezaki T, Kuroda J, Shinojima N, Makino K, Nakamura H, Yano S, Kuratsu J - Cancer Sci. (2014)

Bottom Line: Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential.In both phases, TMZ-FG failed to severely damage normal brain tissue.TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, Honjo, Chuo-ku, Kumamoto, Japan.

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Related in: MedlinePlus

(On the previous page) Immunohistochemical findings on the subcutaneous tumors. (a) Immunohistochemical staining of subcutaneous tumors treated for 7 days with fibrin glue sheets (FGS) that did not (control) and did contain temozolomide (TMZ-FGS). Original magnification, ×400; bar, 50 μm. (b) Positivity ratios of the antibody reactions (n = 3; 10 fields per sample). Analysis was with the unpaired two-tailed t-test. A P < 0.05 was considered statistically significant. **P < 0.001. (c) H&E staining of subcutaneous tumors elicited by transplanted U87MG cells. The mice were treated for 7 days with FGS alone, peroral TMZ (TMZ-PO) or TMZ-FGS. The FGS was placed under the tumors. Similar findings were obtained when Kumamoto-glioma-initiating cell 1 (K-GIC1) or K-GIC2 cells were transplanted (data not shown). Low magnification; bar, 5 mm.
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fig04: (On the previous page) Immunohistochemical findings on the subcutaneous tumors. (a) Immunohistochemical staining of subcutaneous tumors treated for 7 days with fibrin glue sheets (FGS) that did not (control) and did contain temozolomide (TMZ-FGS). Original magnification, ×400; bar, 50 μm. (b) Positivity ratios of the antibody reactions (n = 3; 10 fields per sample). Analysis was with the unpaired two-tailed t-test. A P < 0.05 was considered statistically significant. **P < 0.001. (c) H&E staining of subcutaneous tumors elicited by transplanted U87MG cells. The mice were treated for 7 days with FGS alone, peroral TMZ (TMZ-PO) or TMZ-FGS. The FGS was placed under the tumors. Similar findings were obtained when Kumamoto-glioma-initiating cell 1 (K-GIC1) or K-GIC2 cells were transplanted (data not shown). Low magnification; bar, 5 mm.

Mentions: We used Ki-67, cleaved caspase3, LC3 and p16 as markers for proliferation, apoptosis, autophagy and senescence. At high-power magnification, we counted immunohistochemically positive cells among the tumor cells around the FGS in 10 fields. The Ki-67-positive ratio was lower in all TMZ-treated mice than in the controls. In contrast, the ratio of cleaved caspase 3, LC3 and p16 positivity was higher in TMZ-treated mice than in the controls (Fig.4a,b; Table S2). Changes induced by TMZ were observed mainly on the tumor side covered with the TMZ-FGS. Such findings were not detected in mice treated with FGS only or with oral TMZ only (Fig.4c).


Antitumor effect of fibrin glue containing temozolomide against malignant glioma.

Anai S, Hide T, Takezaki T, Kuroda J, Shinojima N, Makino K, Nakamura H, Yano S, Kuratsu J - Cancer Sci. (2014)

(On the previous page) Immunohistochemical findings on the subcutaneous tumors. (a) Immunohistochemical staining of subcutaneous tumors treated for 7 days with fibrin glue sheets (FGS) that did not (control) and did contain temozolomide (TMZ-FGS). Original magnification, ×400; bar, 50 μm. (b) Positivity ratios of the antibody reactions (n = 3; 10 fields per sample). Analysis was with the unpaired two-tailed t-test. A P < 0.05 was considered statistically significant. **P < 0.001. (c) H&E staining of subcutaneous tumors elicited by transplanted U87MG cells. The mice were treated for 7 days with FGS alone, peroral TMZ (TMZ-PO) or TMZ-FGS. The FGS was placed under the tumors. Similar findings were obtained when Kumamoto-glioma-initiating cell 1 (K-GIC1) or K-GIC2 cells were transplanted (data not shown). Low magnification; bar, 5 mm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4317836&req=5

fig04: (On the previous page) Immunohistochemical findings on the subcutaneous tumors. (a) Immunohistochemical staining of subcutaneous tumors treated for 7 days with fibrin glue sheets (FGS) that did not (control) and did contain temozolomide (TMZ-FGS). Original magnification, ×400; bar, 50 μm. (b) Positivity ratios of the antibody reactions (n = 3; 10 fields per sample). Analysis was with the unpaired two-tailed t-test. A P < 0.05 was considered statistically significant. **P < 0.001. (c) H&E staining of subcutaneous tumors elicited by transplanted U87MG cells. The mice were treated for 7 days with FGS alone, peroral TMZ (TMZ-PO) or TMZ-FGS. The FGS was placed under the tumors. Similar findings were obtained when Kumamoto-glioma-initiating cell 1 (K-GIC1) or K-GIC2 cells were transplanted (data not shown). Low magnification; bar, 5 mm.
Mentions: We used Ki-67, cleaved caspase3, LC3 and p16 as markers for proliferation, apoptosis, autophagy and senescence. At high-power magnification, we counted immunohistochemically positive cells among the tumor cells around the FGS in 10 fields. The Ki-67-positive ratio was lower in all TMZ-treated mice than in the controls. In contrast, the ratio of cleaved caspase 3, LC3 and p16 positivity was higher in TMZ-treated mice than in the controls (Fig.4a,b; Table S2). Changes induced by TMZ were observed mainly on the tumor side covered with the TMZ-FGS. Such findings were not detected in mice treated with FGS only or with oral TMZ only (Fig.4c).

Bottom Line: Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential.In both phases, TMZ-FG failed to severely damage normal brain tissue.TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Kumamoto University Graduate School of Medical Science, Honjo, Chuo-ku, Kumamoto, Japan.

Show MeSH
Related in: MedlinePlus