Last update 01 Nov 2024

LAMA4

Last update 01 Nov 2024

Basic Info

Synonyms

LAMA3, LAMA4, laminin subunit alpha 4

+ [4]

Introduction

Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Drugs associated with LAMA4

AG-101

Target

CD29 x EGFR x LAMA4

Mechanism

CD29 inhibitors [+2]

Active Org.

Arrogene, Inc.

Originator Org.

Cedars-Sinai Health System

Active Indication

Breast Cancer [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

2A3 mAb (Northwestern University)

Target

LAMA4

Mechanism

LAMA4 inhibitors

Active Org.

Northwestern University

Originator Org.

Northwestern University

Active Indication

Neovascularization, Pathologic

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LAMA4

100 Translational Medicine associated with LAMA4

0 Patents (Medical) associated with LAMA4

156

Literatures (Medical) associated with LAMA4

01 Oct 2024·Cancer Medicine

New Anti‐Angiogenic Therapy for Glioblastoma With the Anti‐Depressant Sertraline

Article

Author: Fujimura, Atsushi ; Kurozumi, Kazuhiko ; Date, Isao ; Matsumoto, Yuji ; Michiue, Hiroyuki ; Tsuboi, Nobushige ; Suruga, Yasuki ; Otani, Yoshihiro ; Ishida, Joji ; Matsui, Hideki ; Fujii, Kentaro ; Uneda, Atsuhito

ABSTRACTBackground and AimsAnti‐angiogenic therapies prolong patient survival in some malignancies but not glioblastoma. We focused on the relationship between the differentiation of glioma stem like cells (GSCs) into tumor derived endothelial cells (TDECs) and, anti‐angiogenic therapy resistance. Especially we aimed to elucidate the mechanisms of drug resistance of TDECs to anti‐angiogenic inhibitors and identify novel anti‐angiogenic drugs with clinical applications.ResultsThe mouse GSCs, 005, were differentiated into TDECs under hypoxic conditions, and TDECs had endothelial cell characteristics independent of the vascular endothelial growth factor (VEGF) pathway. In vivo, inhibition of the VEGF pathway had no anti‐tumor effect and increased the percentage of TDECs in the 005 mouse model. Novel anti‐angiogenic drugs for glioblastoma were evaluated using a tube formation assay and a drug repositioning strategy with existing blood–brain barrier permeable drugs. Drug screening revealed that the antidepressant sertraline inhibited tube formation of TDECs. Sertraline was administered to differentiated TDECs in vitro and 005 mouse models in vivo to evaluate genetic changes by RNA‐Seq and tumor regression effects by immunohistochemistry and MRI. Sertraline reduced Lama4 and Ang2 expressions of TDEC, which play an important role in non‐VEGF‐mediated angiogenesis in tumors. The combination of a VEGF receptor inhibitor axitinib, and sertraline improved survival and reduced tumor growth in the 005 mouse model.ConclusionCollectively, our findings showed the diversity of tumor vascular endothelial cells across VEGF and non‐VEGF pathways led to anti‐angiogenic resistance. The combination of axitinib and sertraline can represent an effective anti‐angiogenic therapy for glioblastoma with safe, low cost, and fast availability.

01 Sep 2024·Recent Patents on Anti-Cancer Drug Discovery

Comprehensive Genomic Analysis of Puerarin in Inhibiting Bladder Urothelial Carcinoma Cell Proliferation and Migration

Article

Author: Liu, Ying ; Shi, Zhen-Duo ; Wang, Jing-kai ; Zhang, Ge-jin ; Liu, Peng-fei ; Hao, Lin ; Pang, Kun ; Xu, Hao ; Ding, Ji-cun ; Xu, Peng ; Pan, Deng ; Ma, Yu-yang ; Wang, Hai-luo

Background:Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms.Methods:Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation.Results:A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218μmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patientsConclusion:Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

02 Aug 2024·Journal of Proteome Research

Extracellular Matrix Protein Signatures of the Outer and Inner Zones of the Rat Adrenal Cortex

Article

Author: Freitas, Danilo Henriques de Oliveira ; Lotfi, Claudimara Ferini Pacicco ; Auricino, Thais Barabba ; Kremer, Jean Lucas ; Palmisano, Giuseppe ; Bongiovani Rodrigues, Fernanda ; Santiago, Veronica Feijoli

This study analyzes the extracellular matrix (ECM) signatures of the outer (OF = capsule + subcapsular + zona glomerulosa cells) and inner fractions (IF = zona fasciculata cells) of the rat adrenal cortex, which comprise two distinct microenvironment niches. Proteomic profiles of decellularized OF and IF samples, male and female rats, identified 252 proteins, with 32 classified as ECM-component and ECM-related. Among these, 25 proteins were differentially regulated: 17 more abundant in OF, including Col1a1, Col1a2, Col6a1, Col6a2, Col6a3, Col12a1, Col14a1, Lama5, Lamb2, Lamc1, Eln, Emilin, Fbln5, Fbn1, Fbn2, Nid1, and Ltbp4, and eight more abundant in IF, including Col4a1, Col4a2, Lama2, Lama4, Lamb1, Fn1, Hspg2, and Ecm1. Eln, Tnc, and Nid2 were abundant in the female OF, while Lama2, Lama5, Lamb2, and Lamc1 were more abundant in the male IF. The complex protein signature of the OF suggests areas of tissue stress, stiffness, and regulatory proteins for growth factor signaling. The higher concentrations of Col4a1 and Col4a2 and their role in steroidogenesis should be further investigated in IF. These findings could significantly enhance our understanding of adrenal cortex functionality and its implications for human health and disease. Key findings were validated, and data are available in ProteomeXchange (PXD046828).

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LAMA4

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