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1.
Int J Mol Sci ; 25(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39000458

RESUMO

Despite advances in the genomic classification of breast cancer, current clinical tests and treatment decisions are commonly based on protein-level information. Nowadays breast cancer clinical treatment selection is based on the immunohistochemical (IHC) determination of four protein biomarkers: Estrogen Receptor 1 (ESR1), Progesterone Receptor (PGR), Human Epidermal Growth Factor Receptor 2 (HER2), and proliferation marker Ki-67. The prognostic correlation of tumor-infiltrating T cells has been widely studied in breast cancer, but tumor-infiltrating B cells have not received so much attention. We aimed to find a correlation between immunohistochemical results and a proteomic approach in measuring the expression of proteins isolated from B-cell lymphocytes in peripheral blood samples. Shotgun proteomic analysis was chosen for its key advantage over other proteomic methods, which is its comprehensive and untargeted approach to analyzing proteins. This approach facilitates better characterization of disease-associated changes at the protein level. We identified 18 proteins in B cell lymphocytes with a significant fold change of more than 2, which have promising potential to serve as breast cancer biomarkers in the future.


Assuntos
Linfócitos B , Biomarcadores Tumorais , Neoplasias da Mama , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Feminino , Biomarcadores Tumorais/metabolismo , Linfócitos B/metabolismo , Linfócitos B/imunologia , Proteômica/métodos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Pessoa de Meia-Idade
2.
Int J Mol Sci ; 25(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38928129

RESUMO

Peripheral blood CD8+ T lymphocytes play a crucial role in cell-mediated immunity and tumor-related immune responses in breast cancer. In this study, label-free quantification analysis and gene set enrichment analysis (GSEA) of CD8+ T lymphocytes in the peripheral blood of benign patients and patients with different breast cancer (BC) subtypes, i.e., luminal A, luminal B, and triple-negative breast cancer (TNBC), were performed using nano-UHPLC and Orbitrap mass spectrometry. Differential protein expression in CD8+ T lymphocytes revealed significant downregulation (log2 FC ≥ 0.38 or ≤-0.38, adj. p < 0.05), particularly in proteins involved in cytotoxicity, cytolysis, and proteolysis, such as granzymes (GZMs) and perforin 1 (PRF1). This downregulation was observed in the benign group (GZMH, GZMM, and PRF1) and luminal B (GZMA, GZMH) subtypes, whereas granzyme K (GZMK) was upregulated in TNBC in comparison to healthy controls. The RNA degradation pathway was significantly downregulated (p < 0.05, normalized enrichment score (NES) from -1.47 to -1.80) across all BC subtypes, suggesting a potential mechanism for regulating gene expression during T cell activation. Also, the Sm-like proteins (LSM2, LSM3, and LSM5) were significantly downregulated in the RNA degradation pathway. Proteomic analysis of CD8+ T lymphocytes in peripheral blood across different breast cancer subtypes provides a comprehensive view of the molecular mechanisms of the systemic immune response that can significantly contribute to advancements in the diagnosis, treatment, and prognosis of this disease.


Assuntos
Neoplasias da Mama , Linfócitos T CD8-Positivos , Granzimas , Humanos , Feminino , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Granzimas/metabolismo , Granzimas/genética , Granzimas/sangue , Adulto , Perforina/metabolismo , Perforina/genética , Idoso , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Regulação Neoplásica da Expressão Gênica
3.
Sci Rep ; 11(1): 6835, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767331

RESUMO

We present a study of the ground state and stability of the fractional plateau phase (FPP) with M/Msat = 1/8 in the metallic Shastry-Sutherland system TmB4. Magnetization (M) measurements show that the FPP states are thermodynamically stable when the sample is cooled in constant magnetic field from the paramagnetic phase to the ordered one at 2 K. On the other hand, after zero-field cooling and subsequent magnetization these states appear to be of dynamic origin. In this case the FPP states are closely associated with the half plateau phase (HPP, M/Msat = ½), mediate the HPP to the low-field antiferromagnetic (AF) phase and depend on the thermodynamic history. Thus, in the same place of the phase diagram both, the stable and the metastable (dynamic) fractional plateau (FP) states, can be observed, depending on the way they are reached. In case of metastable FP states thermodynamic paths are identified that lead to very flat fractional plateaus in the FPP. Moreover, with a further decrease of magnetic field also the low-field AF phase becomes influenced and exhibits a plateau of the order of 1/1000 Msat.

4.
Inorg Chem ; 58(22): 15552-15561, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31657910

RESUMO

Endohedral Ga cluster compounds feature nontrivial superconducting states including the two-gap superconductivity similar in nature to MgB2. We use the joint flux synthetic technique to introduce Sn into the Ga matrix and tune the valence electron count in the two new endohedral cluster superconductors Mo8Ga41-xSnx and Mo4Ga21-x-δSnx with critical temperatures of Tc = 8.7 and 5.85 K, respectively. While the former compound is a derivative of the previously known Mo8Ga41 superconductor, where Sn atoms are enclosed inside the Sn@Ga6 octahedral clusters, the latter is a new architecture built upon Mo@Ga9Sn clusters, Ga@Ga12 cuboctahedra, and Sn4 squares. We show that this novel Mo4Ga21-x-δSnx superconductor features strong electron-phonon coupling with the large ratio of 2Δ(0)/(kBTc) = 4.1 similar to that of the Mo8Ga41 superconductor with the closely related crystal structure.

5.
Sci Rep ; 9(1): 13552, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537828

RESUMO

In this paper, the potential existence of two-gap superconductivity in Mo8Ga41 is addressed in detail by means of thermodynamic and spectroscopic measurements. A combination of highly sensitive bulk and surface probes, specifically ac-calorimetry and scanning tunneling spectroscopy (STS), are utilized on the same piece of crystal and reveal the presence of only one intrinsic gap in the system featuring strong electron-phonon coupling. Minute traces of additional superconducting phases detected by STS and also in the heat capacity measured in high magnetic fields on a high-quality and seemingly single-phase crystal might mimic the multigap superconductivity of Mo8Ga41 suggested recently in several studies.

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