Introduction
Pathological features of glioblastoma
Mouse models of glioblastoma
Genetically engineered models
Tumor classification | Transgene | Knockout, knockin | Grade | Incidences | Study |
---|---|---|---|---|---|
Small nodule like glioma | NES-CreER(T2)
| IDH1 R132H knockin | NA* | 100% by 2–6 weeks | Bardella et al. [15] |
Low-grade astrocytoma |
Src transgene | II | 14% by 2.5–65 weeks | Weissenberger et al. [9] | |
GFAP-HRAS
V12
| II | 95% by 16–24 weeks | Ding et al. [10] | ||
High-grade astrocytoma |
Src transgene | III | 10–20% at later | Weissenberger et al. [9] | |
GFAP-HRAS
V12
| Floxed NF1 + Trp53 knockout | III–IV | 100% by 2–16 weeks | Ding et al. [10] | |
GFAP-T121 transgene |
PTEN
+/−
| II–III | 100% by 4–32 weeks | Xiao et al. [55] | |
GFAP-Cre |
NF1 + Trp53 cis
| II–IV | 30–75% by 15–55 weeks | Reilley et al. [56] | |
HRAS
V12 and AKT
| III–IV | 40% by 16–20 weeks | Marumoto et al. [23] | ||
Glioblastoma |
GFAP-Cre | Floxed NF1 + Trp53 knockout | II–IV | 100% by 10–45 weeks | Zhu et al. [13] |
Kras and AKT (RCAS virus) |
Cdkn2a knockout | IV | 42–49% by 12 weeks | Uhrbom et al. [18] | |
PDGFB (RCAS virus) |
Cdkn2a knockout, Trp53 knockout | IV | 100% by 4–7 weeks | Hambardzumyan et al. [19] | |
EGFRvIII(Ad-Cre virus) |
PTEN
F/F
| II–IV | 93% by 6–15 weeks | Wei et al. [21] | |
HRAS
V12 and AKT
|
Trp53 knockout | IV | 100% by 10–13 weeks | Marumoto et al. [23] | |
NES-CreER | Floxed NF1, Floxed PTEN, Floxed Trp53
| III–IV | 100% by 24–56 weeks | Alcantara Llaguno et al. [24] | |
EGFRvIII(Ad-Cre virus) |
Cdkn2a, PTEN
F/F
| IV | 100% by 5–13 weeks | Zhu et al. [57] | |
Low-grade oligodendroglioma | S100b-vERBB transgene | II | 75% by 52 weeks | Weiss et al. [14] | |
PDGFB (RCAS virus) | II | 60% by 12 weeks | Dai et al. [20] | ||
High-grade oligodendroglioma | S100b-vERBB transgene |
Cdkn2a knockout | III | 90% by 4–24 weeks | Weiss et al. [14] |
GFAP-HRAS
V12 + GFAP-EGFRvIII | III | 100% by 2–13 weeks | Ding et al. [11] | ||
Diffuse intrinsic pontine glioma |
PDGFB + H3.3K27M (RCAS virus) Pax3-Tv-a |
Trp53 knockout | II–IV | 73% by 5–12 weeks | Misuraca et al. [25] |
Viral vector-mediated transduction model
Xenograft and allograft models
No | Study | Type | Cell line | Tumor histrogy | Genetic change | Animal model | Therapy | Drug administration method | Injection point of cells | Time of initiating the therapy | Duration of treatment | Observation period |
---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Tateishi et al. [33] | Xenograft | MGG152(TIC*), HT1080(Human cell line) | Recurrent glioblastoma fibrosarcoma | IDH1 mutant(MGG152) IDH1 R132C mutant (HT1080) | SCID mice 7–10-week old female | NAMPT inhibitor | Oral administration (MGG152) intraperitoneal injection (HT1080) | Right striatum (MGG152) right flank (HT1080) | one week (MGG152) tumor diameters reached 5 mm (HT1080) | 1 × /week (MGG152) 4 days/week (HT1080) | About 30 days (MGG152) 17 days (HT1080) |
2 | Ashizawa et al. [34] | Xenograft | GB-SCC010 GB-SCC026 (primary glioblastoma stem cell lines from patients) | Primary glioblastoma | NA***** | NOD-SCID** mice, NOG*** mice 5–6 week old | STAT3 inhibitor | Oral administration | Subcutaneous | Bearing tumor of > 35mm3
| Daily/three weeks | 28 days |
3 | Wykosky et al. [37] | Allograft | Primary ink4a/arf-/- astrocyte (mouse cell line) | Similar to glioblastoma | ΔEGFR-expressing and PTEN wild-type | Athymic mice 6-8 week old female | EGFR inhibitor(gefitinib) | Oral gavage | Cerebral (2 mm lateral and 1 mm anterior to the bregma) | 20 days | 5 days per week | About 50 days |
4 | Plowman et al. [35] | Xenograft | SF-295(Human cell line) U251(Human cell line) | Glioblastoma | NA***** | Athymic mice | Temozolomide BCNU | Oral gavage(TMZ) tail vein injection(BCNU) | Right cerebral hemisphere | 1 day | day 1, day 5, day 9 | 90 days |
5 | Szabo et al. (2016) [39] | Xenograft | LNT-229 (Human cell line) LN-308(Human cell line) | Glioblastoma | Silencing microRNA-adapted shRNA | CD1-Foxn1nu nude mice 6-12 week old | Neutralizing antibodies to VEGF or PIGF | Intraperitoneal injection | Right striatum | NA***** | Twice weekly | 60 days |
6 | Sharpe et al. [41] | Xenograft | BT111(TIC*) BT116(TIC*) | Primary glioblastoma | Unmethylated MGMT(BT111) NA*****(BT116) | NU-Foxn1nu nude mice | Monoamine oxidase B-activated pro-drug | Tail vein injection | Flank postglenoid foramen | 4 weeks (flank model) 90 days (intracranial model) | day 0, day 12, day 23 (flank model) day 115, day 123, day 131 (intracranial model) | 36 days (flank model) 307 days(intracranial model) |
7 | Zeng et al. [58] | Allograft | GL261-Luc(mouse cell line) | Glioblastoma | NA***** | C57BL/6J mice 6-8 week old | Radiation plus anti-PD-1 antibody | Intraperitoneal injection | left striatum(1 mm lateral and 1 mm anterior to the bregma, 3 mm deep from the cortical surface) | 10 days | day 10, day 12, day 14 | 90 days |
8 | Zhang et al. [59] | Xenograft and allograft | LN-319(Human cell line) GL261(mouse cell line) [51] | Glioblastoma | NA***** (LN-319) ErbB2 expression(GL261) | NSG**** mice (LN-319) C57BL/6 mice(GL261) | ErbB2/HER2 -Specific NK Cells | Intratumoral injection | Subcutaneous right striatum (depth of 3 mm) | 7 days | Weekly for 11 weeks (LN-319) weekly for 3 weeks(GL261) | 303 days (LN-319) 200 days (GL261) |
9 | Parrish et al. [60] | Xenograft | GBM12(TIC*) [67] | Primary glioblastoma | MGMT hypermethylated | NA***** | PARP inhibitor (rucaparib) Temozolomide | Intraperitoneal injection oral gavage | Flank cerebral | NA***** | Days 1–5 every 28 days for 3 cycles | 121 days (flank model) 81 days (intracranial model) |
10 | Gupta et al. [61] | Xenograft | GBM12(TIC*) [67] | Primary glioblastoma | TMZ-mgmt High TMZ-mgmt Low | Athymic mice | PARP inhibitor(veliparib) Temozolomide | Flank | Tumor of ~ 100 ± 15mm3
| 5 days every 28days for 3cycles | About 50 days | |
11 | Garros-Regulez et al. [62] | Xenograft | U251(Human cell line) | Glioblastoma | NA***** | Foxn1nu-Foxn1nu nude mice 8 week old | mTOR inhibition(rapamycin) Temozolomide | Intraperitoneal injection | Flank | 1 week | Twice weekly for 12 weeks | About 60 days |
12 | Hashizume et al. [63] | Xenograft | SF7761(TIC*) SF8628(TIC*) GBM43(TIC*) [68] | Primary pediatric human glioma adult glioblastoma | H3F3A k27M mutation H3F3A k27M mutation MGMT unmethylated | Athymic mice 6 week old female | Demethylase inhibitor | Intraperitoneal injection | Flank brain stem | SF7761: about 50 days SF8628: 56 days GBM43: 5 days | SF7761: daily /10 days SF8628: daily /10 days GBM43: daily/7 days | SF7761: 160 days SF8628: 77 days GBM43: 18 days |
13 | Mathieu et al. [64] | Xenograft | Hs683 (Human cell line) U373 (Human cell line) | Glioma (Hs683) glioblastoma (U373) | NA***** | Nude mice (immunocompromised mice) 6 week old female | Bevacizumab Temozolomide | Tail vein injection oral administration | Cerebral | 5 days | 3 times per week for 3 consecutive weeks | 80 days |
14 | Cho et al. [65] | Xenograft | LN443 (Human cell line) | Glioblastoma | Expressing EGFRvIII CT Del1 mutant (by retroviral infection) | SCID mice | Cetuximab erlotinib | Intraperitoneal injection oral administration | Right striatum | 1 week | 3 times per week | 100 days |
15 | Yoshida et al. [66] | Xenograft | glioblastoma | EGFRvIII amplified (GBM39) expressing EGFRvIII (by retroviral infection:U87) wild-type EGFR(GBM12) | Athymic mice 5 week old female | Pan-ERBB inhibitor | Oral administration | Right caudate putamen | 14 days (GBM39) 11 days (U87) 6 days (GBM12) | 2 week (GBM39) 21 days (U87) day 10, day 13, day16,day 20, day 23 (GBM12) | 66 days (GBM39) 32 days (U87) 70 days(GBM12) | |
16 | Joo et al. [42] | Xenograft | Surgical specimens from glioblastoma patients | Glioblastoma | Depending on specimens | NOG*** mice | NA***** | NA***** | cerebral | With in 12 months | NA***** | About 200 weeks |