Research Article

Architectural Heterogeneity in Tumors Caused by Differentiation Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

Figure 1

Photomicrographs of human cancer cell line xenografts A253, H69, A549 along with human HNSCC surgical samples-derived xenografts #17073 and #16653. (Left panels, H&E; middle panels, CD31 immunostaining to visualize microvessels; right panels, CAIX immunostaining to visualize tumor hypoxic regions; original magnifications, × 100). Poorly differentiated H69 (d) is uniformly well vascularised (e) and has no regions of hypoxia (f(a)) in the ~250 mg tumor but has perinecrotic hypoxic regions in larger (>2000 mg) tumor (f(b), arrow). Similar vascular arrangement (k) is seen in viable regions of the poorly differentiated HNSCC #17073 (PDSCC) which though has hypoxic regions ((l), arrow) around the many necrotic regions seen in the growing tumor. In contrast, A253 and A549 have differentiated regions ((a), arrow & (g)) that being avascular ((b), (h), arrows) are hypoxic ((c), (i), arrows). Surgical sample derived well differentiated HNSCC #16653(WDSCC) has a highly differentiated morphology due to presence of many well differentiated ((m), arrow) regions that are avascular (n) and hypoxic ((o), arrow).
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