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The cellular response to the deprivation of L-phenylalanine from the medium in the cultivation of U87-MG, a glioblastoma-like cell line.

ABSTRACT: To optimize the efficacy of boron neutron capture therapy (BNCT), we investigated the optimal conditions for maximizing the uptake of boronophenylalanine (BPA), an analog of L-phenylalanine (L-Phe), in tumor cells. In the cultivation of tumor cell lines, some cell lines, including U87-MG, demonstrated an amplified accumulation of BPA under 24 hours of L-Phe deprivation, which resulted in an enhancement of BNCT efficiency. Consequently, we conducted a comprehensive analysis of the cellular response of U87-MG under L-Phe restriction by RNA-seq.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279293 | GEO | 2025/12/31

REPOSITORIES: GEO

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The cellular response to the deprivation of L-phenylalanine from the medium in the cultivation of SAS, a squamous carcinoma cell line.

Project description:To optimize the efficacy of boron neutron capture therapy (BNCT), we investigated the optimal conditions for maximizing the uptake of boronophenylalanine (BPA), an analog of L-phenylalanine (L-Phe), in tumor cells. In the cultivation of SAS cells, an amplified accumulation of BPA was observed under 24 hours of L-Phe deprivation, which resulted in an enhancement of BNCT efficiency. Consequently, we conducted a comprehensive analysis of the cellular response of SAS under L-Phe restriction by RNA-seq.

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The cellular response to the deprivation of L-phenylalanine from the medium in the cultivation of HaCaT, a keratynocyte cell line.

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Proteomic characterization of SAS-derived extracellular vesicles following treatment with BPA and doses of neutron irradiation

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Boronophenylalanine-Fructose Complex (BPA-F) and/or Sodium Borocaptate (BSH) Followed By Surgery in Treating Patients With Thyroid Cancer, Head and Neck Cancer, or Liver Metastases

Project description:RATIONALE: Diagnostic procedures using boronophenylalanine-fructose complex (BPA-F) and/or sodium borocaptate (BSH) to detect the presence of boron in tumor cells may help determine whether patients who have thyroid cancer, head and neck cancer, or liver metastases may benefit from boron neutron capture therapy. PURPOSE: This phase I trial is studying the side effects of giving BPA-F and/or BSH before surgery to detect boron uptake in tissues of patients with primary, metastatic, or recurrent thyroid cancer, head and neck cancer, or liver metastases from colorectal cancer.

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Irradiated mouse: Irradiated mouse vs. non-irradiated mouse

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Project description:Phe-restriction_U87-MG

| PRJNA1170477 | ENA

Elevated systemic phenylalanine disrupts glutamate-dependent STING signaling in neutrophils and impairs cancer immunotherapy

Project description:Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet acquired immune resistance remains a major barrier to durable response. Here, we identify a previously unrecognized immunometabolic axis in which elevated systemic phenylalanine (Phe) - driven by dietary intake or ICI-induced hepatic dysfunction - promotes immune evasion. Mechanistically, ICI-induced IL-6 and IFN-γ trigger proteasomal degradation of phenylalanine hydroxylase (PAH) via a TOPK-HECTD1 pathway in hepatocytes, leading to increased circulating Phe. Excess Phe suppresses antitumor immunity by impairing STING activation in tumor-associated neutrophils (TANs), through antagonism of glutamate-GRIK1-CaMKIV signaling. We uncover a key STING phosphorylation site (S324/326) essential for ER-to-Golgi trafficking and type I interferon responses, which is disrupted by Phe. These effects are independent of cGAS-cGAMP and define a glutamate-sensing checkpoint in neutrophil immunity. Therapeutically, restoring PAH function using liver-targeted synthetic RNA mimetics of HULC - a noncoding RNA shown to allosterically enhance PAH enzymatic activity - or activating GRIK1 with SYM2081 reprograms the tumor microenvironment, enhances CD8⁺ T cell function, and overcomes ICI resistance. This work reveals hepatic metabolic reprogramming as a central mechanism of immune escape and highlights new therapeutic opportunities to boost immunotherapy efficacy.

2025-07-21 | GSE303168 | GEO

Impact of Bisphenol-A on the Spliceosome and Meiosis of Sperm in the Testis of Adolescent Mice

Project description:Background：Bisphenol-A (BPA) has estrogenic activity and adversely affects humans and animals' reproductive systems and functions. There has been a disagreement with the safety of BPA exposure at Tolerable daily intake (TDI) (0.05 mg/kg/d) value and non-observed adverse effect level (5 mg/kg/d). The current study investigated the effects of BPA exposure at various doses starting from Tolerable daily intake (0.05 mg/kg/d) to the lowest observed adverse effect level (50 mg/kg/d) on the testis development in male mice offspring. The BPA exposure lasted for 63 days from pregnancy day 0 of the dams to post-natal day (PND) 45 of the offspring. Results：The results showed that BPA exposure significantly increased testis and serum BPA contents of PND 45 mice. The spermatogenic cells became loose, and the lumen of seminiferous tubules enlarged when BPA exposure at 0.05 mg/kg/d TDI. BPA exposure at a low dose (0.05 mg/kg/d) significantly reduced the expression of Scp3 proteins and elevated sperm abnormality. The significant decrease in Scp3 suggested that BPA inhibits the transformation of spermatogonia into spermatozoa in the testis. The RNA-seq proved that the spliceosome was significantly inhibited in the testes of mice exposed to BPA. According to the RT-qPCR, BPA exposure significantly reduced the expression of Snrpc and Hnrnpu. Conclusions：This study indicated that long-term BPA exposure at Tolerable daily intake (0.05 mg/kg/d) is not safe because low-dose long-term exposure to BPA inhibits spermatogonial meiosis in mice testis impairs reproductive function in male offspring.

2022-03-19 | GSE198779 | GEO

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