Table 4.
Neuropathologic Findings and HSV Immunohistochemistry for Brains of Group 7 Athymic mice Harboring Human Gliomas Injected with rQNestin34.5v.2 (3.5 × 107 PFU) after CPA Pre-administration
| Braina |
Gliomab |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Mouse No. | Datec | Antigend | CPEe | CD45f | Necrosisg | Antigend | CD45f | Volumeh | Interpretation |
| 754 | 4 | 2 | 2 | 2 | 4 | 2 | 3 | 3% | tumor in striatum is necrotic, HSV, and CD45 antigen+; adjacent brain and injection tract is HSV+ and CD45+; 2nd focus of HSV antigen in brainstem |
| 755 | 4 | 1 | 0 | 1 | 4 | 2 | 2 | 3% | two tumors in striatum that are 90% HSV+; single focus of HSV+ neurons in mesencephalon |
| 756 | 5i | 3 | 1 | 2 | 0 | 0 | 0 | 0 | there is no tumor; injection tract in striatum with HSV+ cells; ventricular spread of virus based upon HSV+ cells in ependyma/subependyma |
| 757 | 5i | 3 | 0 | 0 | 4 | 2 | 3 | 2% | tumor in injection tract is 100% necrotic with strong HSV+/CD45+ signal; HSV+ staining extends from tumor into surrounding neurons, ependymal cells, and subependymal cells |
| 758 | 5i | 3 | 0 | 2 | 4 | 2 | 3 | 1% | tumor in injection tract with 80% necrotic and HSV+/CD45+; HSV+ staining extends from tumor to surrounding neurons with spread along the ependymal cells and subependyma |
| 761 | 17j | 0 | 0 | 0 | 1 | 2 | 2 | 10% | tumor in forebrain is necrotic, HSV+, CD45+; there are other large tumors that are HSV−; cause of death not apparent |
| 762 | 20j | 1 | 0 | 1 | 0 | 0 | 0 | 5% | one limited focus of HSV+ cells adjacent to lateral ventricle; death attributed to multiple HSV− tumors in brainstem |
| 763 | 20j | 3 | 0 | 0 | 1 | 2 | 2 | 30% | tumor in forebrain is 100% necrotic, HSV+, CD45+; other large tumors are HSV−; limited HSV+ cells in brainstem/cortex; cause of death not apparent |
| 766 | 17j | 3 | 0 | 1 | 0 | 0 | 1 | 5% | sporadic HSV+ cells in periventricular areas; death attributed to multiple HSV− tumors in brainstem, meninges |
| 767 | 10j | 3 | 0 | 0 | 1 | 2 | 2 | <5% | HSV+ cells in rostral periventricular areas; rostral necrotic tumor is HSV+, CD45+; death attributed to tumors in the brainstem |
| 768 | 28j | 1 | 0 | 1 | 1 | 0 | 1 | 55% | one focus of HSV+ cells in cortex; death is attributed to large tumor burden |
| 769 | 23j | 0 | 0 | 0 | 1 | 0 | 1 | 50% | death attributed to large tumor burden |
| 770 | 20j | 3 | 1 | 1 | 0 | 0 | 1 | 5% | disseminated HSV+ cells with low CPE and CD45+ infiltrates; death was attributed to virus infection, although cannot exclude tumor localization in brainstem as a cause |
| 771 | 31 | 0 | 0 | 0 | 4 | 2 | 2 | <1% | small tumor in striatum with 100% necrosis and HSV+ staining, with peripheral CD45+ infiltrates |
| 772 | 31 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | no tumor or virus |
| 773 | 29j | 0 | 0 | 0 | 1 | 0 | 1 | 60% | cause of death attributed to large tumor burden and tumor-associated hemorrhage |
| 774 | 19j | 0 | 0 | 0 | 0 | 0 | 0 | 10% | cause of death not apparent |
| 775 | 23j | 2 | 0 | 1 | 1 | 2 | 2 | 35% | large tumor that is necrotic, HSV+ with CD45+ infiltrates; HSV+ cells in brain around tumor; death is attributed to the large tumor burden |
| 776 | 27j | 1 | 0 | 0 | 2 | 2 | 2 | 40% | Tumor with 15% necrosis that is HSV+; two HSV+ neurons in cortex; death attributed to large tumor burden |
| 777 | 35j | 0 | 0 | 0 | 2 | 2 | 1 | <5% | tumor in striatum is necrotic, HSV+; death attributed to multiple brainstem tumors |
| 779 | 29j | 0 | 0 | 0 | 0 | 0 | 0 | 8% | cause of death not apparent |
| 780 | 27j | 0 | 0 | 0 | 1 | 2 | 2 | 50% | large tumors in forebrain with margins that are necrotic, HSV+, CD45+; death is attributed to large tumor burden |
| 781 | 17j | 0 | 0 | 0 | 0 | 0 | 0 | 25% | cause of death not apparent |
| 782 | 24j | 0 | 0 | 0 | 1 | 2 | 2 | 30% | focal tumor is 100% necrotic, HSV+, CD45+; cause of death attributed to tumor-associated edema and hemorrhage |
| 783 | 28j | 0 | 0 | 0 | 1 | 2 | 2 | 55% | one small focus of tumor is necrotic, HSV+; death is attributed to multiple large tumors associated with hemorrhage |
| 785 | 22j | 0 | 0 | 0 | 1 | 0 | 1 | 50% | death is attributed to the high tumor burden. |
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.