The Influence of Race and Sex on the Side Effect Profile of Methotrexate in the Treatment of Uveitis

LaMattina, Kara C.; Escott, Sarah; Malalis, Julia F.; Mai, David; Harada, Yosuke; Goldstein, Debra A.

doi:10.1080/09273948.2018.1498905

Cited by 5 publications

(4 citation statements)

References 21 publications

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“…In addition, we have proved the successful synthesis of each step by thermogravimetric analysis (TGA) of nanoparticles (Supporting Information, Figure S10). The weight reduction of Fe 3 O 4 @ mSiO 2 @Ce6 is 11%, while those of MIP and NIP are 18 4%. It can be speculated that this is caused by CTPB.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Therefore, during the rapid growth of tumor cells, MTX can selectively bind to the active center of DHFR, thereby preventing or inhibiting the binding of dihydrofolate and enzymes, inhibiting its catalytic reduction activity, hindering folate metabolism, interfering with DNA synthesis, thereby achieving the purpose of inhibiting tumor growth (Supporting Information, Figure S1, right). However, the main factors restricting the further development and application of this type of antimetabolites are that their toxic side effects are severe and cancer cells become easily resistant to them. − Therefore, we need to vigorously research and develop new DHFR inhibitors as antimetabolites for tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

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Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase

Qin

Feng

et al. 2021

ACS Appl. Mater. Interfaces

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As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. In the past, it mainly relied on chemical drugs. Here, we propose a new strategy, (3-propanecarboxyl)triphenylphosphonium bromide (CTPB)modified molecularly imprinted polymer nanomedicine (MIP-CTPB). MIP-CTPB prepared by imprinting the active center of DHFR can specifically bind to the active center to block the catalytic activity of DHFR, thereby inhibiting the synthesis of DNA and ultimately inhibiting the tumor growth. The modification of CTPB allows the nanomedicine to be targeted and enriched in mitochondria, where DHFR is abundant. The confocal laser imaging results show that MIP-CTPB can target mitochondria. Cytotoxicity experiments show that MIP-CTPB inhibits HeLa cell proliferation by 42.2%. In vivo experiments show that the tumor volume of the MIP-CTPB-treated group is only one-sixth of that of the untreated group. The fluorescent and paramagnetic properties of the nanomedicine enable targeted fluorescence imaging of mitochondria and T 2 -weighted magnetic resonance imaging of tumors. This research not only opens up a new direction for the application of molecular imprinting, but also provides a new idea for tumor antimetabolic therapy guided by targeted mitochondrial imaging.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase

Qin

Feng

et al. 2021

ACS Appl. Mater. Interfaces

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“…Safety outcomes will be collected in the form of AEs, physical examination and laboratory tests throughout the treatment period and up to 70 days after the last dose in this study. Gender of the subjects will be taken into account 53…”

Section: Methods and Analysismentioning

confidence: 99%

Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study

et al. 2022

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IntroductionNon-infectious uveitis include a heterogeneous group of sight-threatening and incapacitating conditions. Their correct management sometimes requires the use of immunosuppressive drugs (ISDs), prescribed in monotherapy or in combination. Several observational studies showed that the use of ISDs in combination could be more effective than and as safe as their use in monotherapy. However, a direct comparison between these two treatment strategies has not been carried out yet.Methods and analysisThe Combination THerapy with mEthotrexate and adalImumAb for uveitis (CoTHEIA) study is a phase III, multicentre, prospective, randomised, single-blinded with masked outcome assessment, parallel three arms with 1:1:1 allocation, active-controlled, superiority study design, comparing the efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis. We aim to recruit 192 subjects. The duration of the treatment and follow-up will last up to 52 weeks, plus 70 days follow-up with no treatment. The complete and maintained resolution of the ocular inflammation will be assessed by masked evaluators (primary outcome). In addition to other secondary measurements of efficacy (quality of life, visual acuity and costs) and safety, we will identify subjects’ subgroups with different treatment responses by developing prediction models based on machine learning techniques using genetic and proteomic biomarkers.Ethics and disseminationThe protocol, annexes and informed consent forms were approved by the Reference Clinical Research Ethic Committee at the Hospital Clínico San Carlos (Madrid, Spain) and the Spanish Agency for Medicines and Health Products. We will elaborate a dissemination plan including production of materials adapted to several formats to communicate the clinical trial progress and findings to a broad group of stakeholders. The promoter will be the only access to the participant-level data, although it can be shared within the legal situation.Trial registration number2020-000130-18; NCT04798755.

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“…Indeed, methotrexate was previously used for the treatment of cancer [36,37]. Although the dose of methotrexate used in RA is lower than the dose used for oncology, long treatment durations often result in adverse effects, such as hair loss, nausea or headaches [38]. Furthermore, methotrexate is a long-known teratogen and abortifacient, which complicates the combination of pregnancy and the disease [39].…”

Section: Introductionmentioning

confidence: 99%

Fighting rheumatoid arthritis: Kv1.3 as a therapeutic target

Serrano-Albarrás

Cirera-Rocosa

Sastre

et al. 2019

Biochemical Pharmacology

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The Influence of Race and Sex on the Side Effect Profile of Methotrexate in the Treatment of Uveitis

Abstract: While our sample was small, these findings suggest racial and gender disparities in the side effects experienced by patients treated with methotrexate. This information may be useful to clinicians counseling patients on risk profile.

Cited by 5 publications

References 21 publications

Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase

Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase

Efficacy, safety and cost-effectiveness of methotrexate, adalimumab or their combination in non-infectious non-anterior uveitis: a protocol for a multicentre, randomised, parallel three arms, active-controlled, phase III open label with blinded outcome assessment study

Fighting rheumatoid arthritis: Kv1.3 as a therapeutic target

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