Prognostic significance of L-type amino acid transporter-1 (LAT-1) expression in human astrocytic gliomas

Faried, Ahmad; Bolly, Hendrikus Masang Ban; Hermanto, Yulius; Achmad, Arifudin; Halim, Danny; Tjahjono, Firman Priguna; Agustina, Hasrayati; Kartamihardja, Achmad Hussein Sundawa; Arifin, Muhammad Zafrullah

doi:10.1016/j.inat.2020.100939

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…34 Study conducted by Faried et al, showed that high expression of LAT-1 is associated with poor survival in glioma patients; hence, it can increase proliferation in malignant glial cells and contribute to further activation of PDL-1, which further increases the proliferation of glioma. 35…”

Section: Other Biomarkersmentioning

confidence: 99%

The Overall Survival Rate Prognosis in Diffuse Astrocytic Patients Based on Isocitrate Dehydrogenase-1 Mutation Status (IDH1 R132H): An Indonesian Multicenter Study

Faried,

Hermanto,

Gill

et al. 2023

Preprint

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Objective: The IDH1 mutation status is one of the main factors indicated the prognosis of patients with astrocytic malignancies; yet, targeted sequencing is not readily available in countries with limited resources. We aimed to analyze the association between examination IDH1 status and the overall survival rates of diffuse astrocytic tumor patients. Methods: This retrospective cohort multicenter study included 327 diffuse astrocytic tumor patients, January 2017 – December 2022. The immunohistochemistry or PCR data of IDH1 mutation and MGMT status, WHO classification, and Karnofsky performance score (KPS) were collected. Statistical analysis was then performed to analyze their association with the median of follow-up time of 18-months. Result: At 36-month follow-up, the overall survival rate of patients with WHO grade IV (29.23%) was significantly lower than patients with WHO grade III and II (72.24% and 82.46%; p < 0.0001). The diffuse astrocytic tumor patients’ survival rate was also significantly influenced by the KPS score (HR 1.64 [1.08 – 2.50]; p = 0.0208). The survival rate of patients with IDH1 wildtype was significantly lower than that of patients with IDH1 mutant (HR 2.13 [1.51 – 3.00]; p = 0.0004). The overall survival rate of patients with IDH1 wildtype and wildtype MGMT unmethylated was significantly lower than patients with IDH1 mutant MGMT methylated (p < 0.0001). Conclusion: Examination of IDH1-R132H mutant is a reliable examination to predict the survival prognosis in patients with IDH1 mutant vs IDH1 wildtype; this examination could be used as an alternative to the recommended targeted sequencing of IDH1.

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Section: Other Biomarkersmentioning

confidence: 99%

The Overall Survival Rate Prognosis in Diffuse Astrocytic Patients Based on Isocitrate Dehydrogenase-1 Mutation Status (IDH1 R132H): An Indonesian Multicenter Study

Faried,

Hermanto,

Gill

et al. 2023

Preprint

Self Cite

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A Water-Soluble Small Molecule Boron Carrier Targeting Biotin Receptors for Neutron Capture Therapy

Nishimura,

Tanaka,

Miura

et al. 2024

ACS Omega

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Synthesis, Cytotoxicity, and Mechanistic Evaluation of Tetrahydrocurcumin-Amino Acid Conjugates as LAT1-Targeting Anticancer Agents in C6 Glioma Cells

Teerawonganan,

Hasriadi,

Dasuni Wasana

et al. 2024

IJMS

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Glioblastoma, a fatal brain cancer with limited treatments and poor prognosis, could benefit from targeting the L-type amino acid transporter I (LAT1). LAT1 is essential for cancer cells to acquire necessary amino acids. Tetrahydrocurcumin (THC), a key curcumin derivative, shows potential for glioblastoma treatment. However, its effectiveness is hindered by poor physicochemical and pharmacokinetic properties. Therefore, this study aims to improve the therapeutic efficacy of THC against glioblastoma by chemically modifying it to target LAT1. A novel series of THC-amino acid conjugates were synthesized by conjugating five amino acids: glycine, leucine, isoleucine, and phenylalanine to THC via carbamate bonds. The therapeutic efficacy of THC-amino acid conjugates was further examined in C6 glioma cells, including the role of LAT1 in their therapeutic effects. Among the conjugates tested, THC conjugated with two phenylalanines (THC-di-Phe) showed remarkably higher cytotoxicity against C6 glioma cells (35.8 μM) compared to THC alone (110.7 μM). THC-di-Phe induced cellular death via necrosis and apoptosis, outperforming THC. Additionally, THC-di-Phe inhibited C6 cell proliferation and migration more effectively than THC. Co-incubation of THC-di-Phe with the LAT1 inhibitor 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) further increased cellular death. THC-di-Phe also significantly inhibited the P70SK/S6 pathway, regulated by LAT1 inhibitors, more effectively than THC and displayed a similar binding mode with both JX-075 and BCH to the active site of LAT1. Findings suggest the potential role of THC-di-Phe as a LAT1 inhibitor and provide novel insight into its use as a potent antitumor agent in glioma with increased therapeutic efficacy.

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Prognostic significance of L-type amino acid transporter-1 (LAT-1) expression in human astrocytic gliomas

Cited by 3 publications

References 29 publications

The Overall Survival Rate Prognosis in Diffuse Astrocytic Patients Based on Isocitrate Dehydrogenase-1 Mutation Status (IDH1 R132H): An Indonesian Multicenter Study

The Overall Survival Rate Prognosis in Diffuse Astrocytic Patients Based on Isocitrate Dehydrogenase-1 Mutation Status (IDH1 R132H): An Indonesian Multicenter Study

A Water-Soluble Small Molecule Boron Carrier Targeting Biotin Receptors for Neutron Capture Therapy

Synthesis, Cytotoxicity, and Mechanistic Evaluation of Tetrahydrocurcumin-Amino Acid Conjugates as LAT1-Targeting Anticancer Agents in C6 Glioma Cells

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