Table 3.
Neuropathologic Findings and HSV Immunohistochemistry for Brains of Athymic Mice Harboring Human Gliomas Injected with rQNestin34.5v.2 (3.5 × 10E7 PFUs)
| Braina |
Gliomab |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Mouse No. | Datec | Antigend | CPEe | CD45f | Necrosisg | Antigend | CD45e | Volumeh | Interpretation |
| 653 | 4 | 0 | 0 | 0 | 4 | 2 | 3 | 6% | tumor in striatum; 80% of tumor is HSV antigen+ and necrotic |
| 654 | 4 | 3 | 0 | 3 | 2–3 | 2 | 3 | 5% | extension of HSV from tumor to ependymal with spread through ventricular system (ventricular spread); 50% of tumor is necrotic and HSV antigen+ |
| 655 | 4 | 3 | 2 (adjacent to tumor) | 3 | 4 | 2 | 3 | 6% | extension of HSV from tumor to ependymal with ventricular spread; 80% of tumor is necrotic and HSV antigen+ |
| 659 | 5i | 3 | 3 | 3 | 4 | 2 | 3 | 4% | extension of HSV from tumor to ependymal cells with ventricular spread; 100% of tumor is necrotic and HSV antigen+ |
| 660 | 5i | 3 | 0 | 3 | 4 | 2 | 3 | 1.5% | extension of HSV from tumor to ependymal with ventricular spread; two tumor nodules: one is 100% necrotic and HIV antigen+ |
| 661 | 19j | 3 | 0 | 2 | 0 | 0 | 0 | 10% | mild periventricular distribution of viral antigen; Tumor in brainstem is large and likely cause of death |
| 662 | 31 | 0 | 0 | 0 | 4 | 2 | 1 | 1% | single necrotic tumor in striatum that is HSV antigen+ |
| 663 | 28j | 0 | 0 | 0 | 2 | 2 | 0 | 25% | several nodules with two that are 100% necrotic and HSV+; cause of death due to tumor edema/hemorrhage |
| 664 | 24j | 0 | 0 | 0 | 1 | 2 | 2 | 25% | one tumor nodule is 100% necrotic and HSV antigen+; others exhibit partial necrosis but are HSV antigen−; death attributed to white matter edema associated with tumor |
| 665 | 23j | 0 | 0 | 0 | 2 | 2 | 2 | 55% | multiple tumor nodules with variable necrosis, and necrotic foci are both HSV antigen+ HSV antigen−; death is attributed to high tumor burden and associated hemorrhage |
| 666 | 21j | 0 | 0 | 0 | 2 | 2 | 3 | 45% | extensive tumor necrosis (45%) that is viral antigen+; death is attributed to the high tumor burden |
| 669 | 18jj | 0 | 0 | 0 | 0 | 0 | 0 | 50% | death is attributed to the high tumor burden |
| 670 | 23j | 0 | 0 | 0 | 2 | 2 | 2 | 30% | multiple tumor foci, 45% necrosis with regions that are HSV antigen− and HSV antigen+; death is attributed to the high tumor burden |
| 671 | 31 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | there is evidence of an inoculation track in striatum but no tumor or HSV |
| 673 | 24j | 2 | 2 | 2 | 1 | 2 | 2 | 15% | two tumor nodules with necrosis associated with HSV antigen (one complete, the other10%); forebrain with focus HSV+ cells, CPE, and inflammation, but evidence of extensive viral dissemination is lacking; cause of death is not apparent |
| 675 | 19j | 0 | 0 | 0 | 0 | 0 | 0 | 25% | death is attributed to the high tumor burden in the brainstem |
| 676 | 14j | 1 | – | 2 | 1 | 2 | 2 | 5% | tumor necrosis that is HSV antigen+, with limited viral spread into adjacent brain; cause of death not apparent |
| 677 | 31 | 0 | 0 | 0 | 1 | 2 | 3 | 26% | large tumor nodule 100% necrotic and HSV antigen+ |
| 678 | 16j | 0 | 0 | 0 | 3 | 2 | 2 | 30% | one large and one small tumor nodule (50% and 100% necrosis, respectively) that are HSV antigen+; cause of death not apparent |
| 679 | 61 | 0 | 0 | 0 | 4 | 2 | 3 | <1% | small necrotic tumor that is weakly HSV antigen+ and associated with intense CD45+ immunoreactivity |
| 680 | 7j | 3 | 1 | 2 | 1 | 2 | 2 | <10% | multiple tumor nodules in brainstem that are HSV antigen+ and associated CD45+ infiltrates; some HSV antigen in periventricular areas; death attributed to tumor-associated edema and hemorrhage |
| 682 | 41j | 0 | 0 | 0 | 1 | 2 | 0 | 50% | large tumor masses, where necrosis is associated with HSV antigen but no CD45+ infiltrates; death attributed to effects of tumor burden |
| 683 | 32j | 0 | 0 | 0 | 0 | 0 | 0 | 20% | death attributed to effects of tumor burden |
| 684 | 10j | 3 | 2 | 3 | 0 | 0 | 0 | low | low tumor volume in brainstem; evidence of ventricular dissemination of HSV with CPE and inflammation, particularly in brainstem; death attributed to virus infection |
| 685 | 22j | 2 | 0 | 0 | 1 | 0 | 1 | 50% | large tumors associated with edema and hemorrhage that are the cause of death |
| 686 | 48j | 0 | 0 | 0 | 1 | 0 | 1 | 30% | death attributed to effects of tumor burden |
| 687 | 20j | 0 | 0 | 0 | 1 | 0 | 1 | 55% | death attributed to tumor-associated edema, hemorrhage, and necrosis of parenchyma (infarction) |
| 689 | 23j | 0 | 0 | 0 | 1 | 2 | 1 | 25% | one nodule of tumor is necrotic and HSV antigen+; death attributed to tumor-associated edema and hemorrhage |
| 690 | 39j | 0 | 0 | 0 | 0 | 0 | 1 | 25% | death attributed to tumor-associated edema and hemorrhage |
| 691 | 26j | 0 | 0 | 0 | 0 | 0 | 0 | 15% | death attributed to brainstem localization of tumor and associated edema |
All analyses were conducted by Dr. M. Oglesbee (Ohio State University College of Veterinary Medicine).
a
Brain pathology.
b
Glioma pathology.
c
Date of scheduled euthanasia or unexpected death from time of rQNestin34.5v.2 injection.
d
HSV antigen (scored 0–3) (see Materials and Methods for explanation of scores).
e
Viral cytopathic effect (scored 0–3).
f
CD45+ cells, suggestive of activated microglia/inflammation (scored 0–3).
g
Necrosis (scored 0–3).
h
Estimated percent of brain occupied by glioma.
i
Scheduled necropsies conducted on day 5 rather than day 4.
j
Premature death or euthanasia for moribund state.