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Prevention of cancer recurrence in tumor margins by stopping microcirculation in the tumor and tumor-host interface.

Hori K, Akita H, Nonaka H, Sumiyoshi A, Taki Y - Cancer Sci. (2014)

Bottom Line: Treatment in the reverse order, however, did not affect T-HI vessel blood flow.The greatest difference between the two treatments was the occurrence of gradual T-HI edema with the former.Severe T-HI edema compressed T-HI blood vessels, so that circulation stopped.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Science, Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

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Fine structure of microvessels at 24 h after 10 mg/kg combretastatin derivative (Cderiv) treat-ment. (a) Light microscopic images of tissue in and around the tumor–host interface (T-HI) in a LY80 tumor. White dashed line, tumor boundary. Scale bar = 200 μm. (I) Inner region; (II) marginal region; (III) T-HI; and (IV) s.c. tissue. (b) Electron microscopic images of typical endothelial cells (E) in a vessel in four regions. (I) Endothelial cells in the inner region. P, pericyte; R, red blood cell. Arrows, debris from intracellular organelles; asterisk, gap formed in the cytoplasm. (II) Endothelial cells in the tumor margin. (III) Endothelial cells in the T-HI. L, vascular lumen. Arrows, vesiculo-vacuolar organelles. (IV) Endothelial cells in s.c. tissue. Scale bar = 1 μm.
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fig03: Fine structure of microvessels at 24 h after 10 mg/kg combretastatin derivative (Cderiv) treat-ment. (a) Light microscopic images of tissue in and around the tumor–host interface (T-HI) in a LY80 tumor. White dashed line, tumor boundary. Scale bar = 200 μm. (I) Inner region; (II) marginal region; (III) T-HI; and (IV) s.c. tissue. (b) Electron microscopic images of typical endothelial cells (E) in a vessel in four regions. (I) Endothelial cells in the inner region. P, pericyte; R, red blood cell. Arrows, debris from intracellular organelles; asterisk, gap formed in the cytoplasm. (II) Endothelial cells in the tumor margin. (III) Endothelial cells in the T-HI. L, vascular lumen. Arrows, vesiculo-vacuolar organelles. (IV) Endothelial cells in s.c. tissue. Scale bar = 1 μm.

Mentions: As Figure2 illustrates, all tumor vessels lost circulatory functions approximately 24 h after 10 mg/kg Cderiv treatment, but the function of vessels in the T-HI remained intact. To elucidate how the fine structure of microvessels changed at that time, we observed, using electron microscopy, vessels in different regions: a tumor region that was more than 200 μm away from the tumor boundary (Fig.3a-I); a tumor margin within 200 μm of the boundary (Fig.3a-II); a non-tumor region within 200 μm of the boundary, that is, the T-HI (Fig.3a-III); and an s.c. region that was more than 200 μm away from the tumor boundary (Fig.3a-IV). We obtained the typical microvessels in Figure3(b) from the regions shown in Figure3(a). In tumors, lumens of vessels in both the inner region (Fig.3b-I) and the marginal region (Fig.3b-II) disappeared after Cderiv treatment, and endothelial cells were in direct contact with residual erythrocytes. In contrast, lumens of vessels in the T-HI (Fig.3b-III) and subcutis (Fig.3b-IV) did not close. These observations support the vital microscopic findings that Cderiv stopped tumor blood circulation but did not stop blood flow in non-tumor blood vessels. Endothelial damage was more prominent in tumor vessels in the inner region (Fig.3b-I) compared with tumor vessels in the marginal region (Fig.3b-II). Tumor vessels in the inner region had many endothelial cells with gaps, deformed endoplasmic reticulum, and debris within the cytoplasm. These findings indicate that severe tumor vessel degradation occurred in the inner tumor region. A characteristic finding for vascular endothelial cells in the T-HI was the presence of a large number of vesiculo-vacuolar organelles (VVOs) in the cytoplasm (Fig.3b-III). The VVO is an intracellular organelle involved in endocytosis.28


Prevention of cancer recurrence in tumor margins by stopping microcirculation in the tumor and tumor-host interface.

Hori K, Akita H, Nonaka H, Sumiyoshi A, Taki Y - Cancer Sci. (2014)

Fine structure of microvessels at 24 h after 10 mg/kg combretastatin derivative (Cderiv) treat-ment. (a) Light microscopic images of tissue in and around the tumor–host interface (T-HI) in a LY80 tumor. White dashed line, tumor boundary. Scale bar = 200 μm. (I) Inner region; (II) marginal region; (III) T-HI; and (IV) s.c. tissue. (b) Electron microscopic images of typical endothelial cells (E) in a vessel in four regions. (I) Endothelial cells in the inner region. P, pericyte; R, red blood cell. Arrows, debris from intracellular organelles; asterisk, gap formed in the cytoplasm. (II) Endothelial cells in the tumor margin. (III) Endothelial cells in the T-HI. L, vascular lumen. Arrows, vesiculo-vacuolar organelles. (IV) Endothelial cells in s.c. tissue. Scale bar = 1 μm.
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fig03: Fine structure of microvessels at 24 h after 10 mg/kg combretastatin derivative (Cderiv) treat-ment. (a) Light microscopic images of tissue in and around the tumor–host interface (T-HI) in a LY80 tumor. White dashed line, tumor boundary. Scale bar = 200 μm. (I) Inner region; (II) marginal region; (III) T-HI; and (IV) s.c. tissue. (b) Electron microscopic images of typical endothelial cells (E) in a vessel in four regions. (I) Endothelial cells in the inner region. P, pericyte; R, red blood cell. Arrows, debris from intracellular organelles; asterisk, gap formed in the cytoplasm. (II) Endothelial cells in the tumor margin. (III) Endothelial cells in the T-HI. L, vascular lumen. Arrows, vesiculo-vacuolar organelles. (IV) Endothelial cells in s.c. tissue. Scale bar = 1 μm.
Mentions: As Figure2 illustrates, all tumor vessels lost circulatory functions approximately 24 h after 10 mg/kg Cderiv treatment, but the function of vessels in the T-HI remained intact. To elucidate how the fine structure of microvessels changed at that time, we observed, using electron microscopy, vessels in different regions: a tumor region that was more than 200 μm away from the tumor boundary (Fig.3a-I); a tumor margin within 200 μm of the boundary (Fig.3a-II); a non-tumor region within 200 μm of the boundary, that is, the T-HI (Fig.3a-III); and an s.c. region that was more than 200 μm away from the tumor boundary (Fig.3a-IV). We obtained the typical microvessels in Figure3(b) from the regions shown in Figure3(a). In tumors, lumens of vessels in both the inner region (Fig.3b-I) and the marginal region (Fig.3b-II) disappeared after Cderiv treatment, and endothelial cells were in direct contact with residual erythrocytes. In contrast, lumens of vessels in the T-HI (Fig.3b-III) and subcutis (Fig.3b-IV) did not close. These observations support the vital microscopic findings that Cderiv stopped tumor blood circulation but did not stop blood flow in non-tumor blood vessels. Endothelial damage was more prominent in tumor vessels in the inner region (Fig.3b-I) compared with tumor vessels in the marginal region (Fig.3b-II). Tumor vessels in the inner region had many endothelial cells with gaps, deformed endoplasmic reticulum, and debris within the cytoplasm. These findings indicate that severe tumor vessel degradation occurred in the inner tumor region. A characteristic finding for vascular endothelial cells in the T-HI was the presence of a large number of vesiculo-vacuolar organelles (VVOs) in the cytoplasm (Fig.3b-III). The VVO is an intracellular organelle involved in endocytosis.28

Bottom Line: Treatment in the reverse order, however, did not affect T-HI vessel blood flow.The greatest difference between the two treatments was the occurrence of gradual T-HI edema with the former.Severe T-HI edema compressed T-HI blood vessels, so that circulation stopped.

View Article: PubMed Central - PubMed

Affiliation: Division of Cancer Science, Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.

Show MeSH
Related in: MedlinePlus