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1.
Lab Invest ; 104(9): 102126, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39174007

RESUMO

This study used artificial intelligence (AI)-based analysis to investigate the immune microenvironment in endometrial cancer (EC). We aimed to evaluate the potential of AI-based immune metrics as prognostic biomarkers. In total, 296 cases with EC were classified into 4 molecular subtypes: polymerase epsilon ultramutated (POLEmut), mismatch repair deficiency (MMRd), p53 abnormal (p53abn), and no specific molecular profile (NSMP). AI-based methods were used to evaluate the following immune metrics: total tumor-infiltrating lymphocytes (TIL), intratumoral TIL, stromal TIL, and tumor cells using Lunit SCOPE IO, as well as CD4+, CD8+, and FOXP3+ T cells using immunohistochemistry (IHC) by QuPath. These 7 immune metrics were used to perform unsupervised clustering. PD-L1 22C3 IHC expression was also evaluated. Clustering analysis demonstrated 3 distinct immune microenvironment groups: immune active, immune desert, and tumor dominant. The immune-active group was highly prevalent in POLEmut, and it was also seen in other molecular subtypes. Although the immune-desert group was more frequent in NSMP and p53mut, it was also detected in MMRd and POLEmut. POLEmut showed the highest levels of CD4+ and CD8+ T cells, total TIL, intratumoral TIL, and stromal TIL with the lowest levels of FOXP3+/CD8+ ratio. In contrast, p53abn in the immune-active group showed higher FOXP3+/CD4+ and FOXP3+/CD8+ ratios. The immune-active group was associated with favorable overall survival and recurrence-free survival. In the NSMP subtype, a significant association was observed between immune active and better recurrence-free survival. The PD-L1 22C3 combined positive score (CPS) showed significant differences among the 3 groups, with the immune-active group having the highest median CPS and frequency of CPS ≥ 1%. The immune microenvironment of EC was variable within molecular subtypes. Within the same immune microenvironment group, significant differences in immune metrics and T cell composition were observed according to molecular subtype. AI-based immune microenvironment groups served as prognostic markers in ECs, with the immune-active group associated with favorable outcomes.


Assuntos
Neoplasias do Endométrio , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Humanos , Feminino , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Microambiente Tumoral/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Pessoa de Meia-Idade , Idoso , Adulto , Biomarcadores Tumorais/metabolismo
2.
Phys Chem Chem Phys ; 15(3): 957-64, 2013 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-23207427

RESUMO

Electronic and vibrational spectra of acetaminophen were measured by using UV-UV hole burning (HB) and IR dip spectroscopy. HB spectra show the coexistence of 4 different species, which include two new ones. Low-frequency transitions in the spectra are reproduced by a one-dimensional periodic potential with a free-rotor basis set for the methyl group. From the analysis, we concluded that acetaminophen has two conformers and each conformer gives two independent transitions starting from the most stable 0a(1) and the hot 1e internal rotational levels. It is also found that the HB spectrum of the trans-conformer in the previous report is that from the 1e excited level, while the HB spectrum of the cis-conformer is contaminated by the transitions of the trans-conformer. Potential curves of the methyl rotational motion are determined both in S(0) and S(1).


Assuntos
Acetaminofen/química , Gases/química , Espectrofotometria Infravermelho , Raios Ultravioleta , Termodinâmica
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