Inhibition of laminin-8 in vivo using a novel poly(malic acid)-based carrier reduces glioma angiogenesis

  title={Inhibition of laminin-8 in vivo using a novel poly(malic acid)-based carrier reduces glioma angiogenesis},
  author={Manabu Fujita and Natalya M. Khazenzon and Alexander V. Ljubimov and Bong-Seop Lee and Ismo Virtanen and Eggehard Holler and Keith L. Black and Julia Y. Ljubimova},
We have previously shown that laminin-8, a vascular basement membrane component, was overexpressed in human glioblastomas multiforme and their adjacent tissues compared to normal brain. Increased laminin-8 correlated with shorter glioblastoma recurrence time and poor patient survival making it a potential marker for glioblastoma diagnostics and prediction of disease outcome. However, laminin-8 therapeutic potential was unknown because the technology of blocking the expression of multi-chain… 
Blockade of a Laminin-411-Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk.
It is shown that depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice and significantly increased survival of host animals compared with mice with untreated cells.
Alpha4 chain laminins are widely expressed in renal cell carcinomas and have a de-adhesive function
The results suggest that α4 chain Lms have a de-adhesive function and could thus play a role in detachment, migration and invasion of renal carcinoma cells in vivo.
Brain tumor tandem targeting using a combination of monoclonal antibodies attached to biopoly(beta-L-malic acid).
Inhibition of brain tumor growth by intravenous poly(β-l-malic acid) nanobioconjugate with pH-dependent drug release
The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy ofglioma treatment.
Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer.
Polymalic acid nanobioconjugate for simultaneous inhibition of tumor growth and immunostimulation in HER2/neu-positive breast cancer✩
A new nanobioconjugate of the Polycefin family of anti-cancer drugs based on biodegradable and non-toxic polymalic acid (PMLA) was engineered for a multipronged attack on HER2/neu-positive breast cancer cells and was capable of eliciting anti-tumor activity in immunocompetent mice bearing IL-2.
MiR-124-5p inhibits the growth of high-grade gliomas through posttranscriptional regulation of LAMB1.
The findings indicate that miR-124-5p functions as a tumor suppressor and could serve as a molecular marker for glioma diagnosis and as a potential therapeutic target in GBM treatment.
Senescence-induced alterations of laminin chain expression modulate tumorigenicity of prostate cancer cells.
It is demonstrated that senescent prostate epithelial cells can alter the microenvironment and that these changes modulate progression of prostate cancer.
Downregulation of a newly identified laminin, laminin‐3B11, in vascular basement membranes of invasive human breast cancers
Results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis, as well as IL‐1β and TGF‐α, upregulated the α4 expression in vascular endothelial cells.
Nanoconjugate based on polymalic acid for tumor targeting.


Antisense inhibition of laminin-8 expression reduces invasion of human gliomas in vitro.
The results show that laminin-8 may contribute to glioma progression and recurrence not only as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.
Overexpression of β1-chain-containing laminins in capillary basement membranes of human breast cancer and its metastases
Similar to high-grade brain gliomas, the expression of laminin-8 (and lamin in-10) in breast cancer tissue may be a predictive factor for tumor neovascularization and invasion and suggest that laminationin-2, laminine-8, and laminIn-10 are important components of tumor microvessels and may associate with breast tumor progression.
Antiangiogenic Drugs Synergize with a Membrane Macrophage Colony-Stimulating Factor-Based Tumor Vaccine to Therapeutically Treat Rats with an Established Malignant Intracranial Glioma1
Animals that rejected the established T9/9L glioma by the combination therapy proved immune against an intracranial rechallenge by T9/, but showed no resistance to an unrelated MADB106 breast cancer.
Targeting angiogenesis with a conjugate of HPMA copolymer and TNP-470
A water-soluble conjugate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, Gly-Phe-Leu-Gly linker and T NP-470 substantially enhanced and prolonged the activity of TNP-470 in vivo in tumor and hepatectomy models.
Intravenous RNA Interference Gene Therapy Targeting the Human Epidermal Growth Factor Receptor Prolongs Survival in Intracranial Brain Cancer
Purpose: The human epidermal growth factor receptor (EGFR) plays an oncogenic role in solid cancer, including brain cancer. The present study was designed to prolong survival in mice with
Polycefin, a new prototype of a multifunctional nanoconjugate based on poly(beta-L-malic acid) for drug delivery.
In vitro experiments using two human glioma cell lines U87MG and T98G demonstrated that Polycefin was delivered into the tumor cells by a receptor-mediated endocytosis mechanism and was able to inhibit the synthesis of laminin-8 alpha4 and beta1 chains at the same time.
Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo
Smac agonists are promising candidates for cancer therapy by potentiating cytotoxic therapies by enhancing the antitumor activity of Apo-2L/tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) in an intracranial malignant glioma xenograft model in vivo.
Localization of c-Myb and Induction of Apoptosis by Antisense Oligonucleotide c-myb After Angioplasty of Porcine Coronary Arteries
Previous studies have shown that inhibition of the proto-oncogene c-myb inhibits neointimal formation in various animal models. However, the temporal and spatial expression of c-Myb in the vessel
Association between laminin‐8 and glial tumor grade, recurrence, and patient survival
One of these laminins, laminin‐8, was found to be present in highly invasive and malignant glioblastoma multiforme (GBM) (Grade 4 astrocytoma); its expression was associated with a decreased time to tumor recurrence, and it was found in vitro to promote invasion of GBM cell lines.
HPMA copolymer delivery of chemotherapy and photodynamic therapy in ovarian cancer.
The authors' studies document a unique and unexpected advantage of the combination of HPMA copolymer bound doxorubicin with mesochlorin e6/photodynamic therapy in the treatment of ovarian cancer, and predict an exciting future for this novel drug delivery system.