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1.
Int J Mol Sci ; 24(9)2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37175653

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that arises from the cells lining the tubes of the kidney. The tumor immune microenvironment (TIME) of ccRCC is a complex interplay of various immune cells, cytokines, and signaling pathways. One of the critical features of the ccRCC TIME is the presence of infiltrating immune cells, including T cells, B cells, natural killer cells, dendritic cells, and myeloid-derived suppressor cells. Among these cells, CD8+ T cells are particularly important in controlling tumor growth by recognizing and killing cancer cells. However, the TIME of ccRCC is also characterized by an immunosuppressive environment that hinders the function of immune cells. Several mechanisms contribute to the immunosuppressive nature of the ccRCC TIME. For instance, ccRCC cells produce cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), which suppress immune cell activation and promote the differentiation of regulatory T cells (Tregs). Tregs, in turn, dampen the activity of effector T cells and promote tumor growth. In addition, ccRCC cells can express programmed death-ligand 1 (PD-L1), which interacts with the programmed cell death protein 1 (PD-1) receptor on T cells to inhibit their function. In addition, other immune checkpoint proteins, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and lymphocyte activation gene 3 (LAG-3), also contribute to the immunosuppressive milieu of the ccRCC TIME. Finally, the hypoxic and nutrient-poor microenvironment of ccRCC can stimulate the production of immunosuppressive metabolites, such as adenosine and kynurenine, which further impair the function of immune cells. Understanding the complex interplay between tumor cells and the immune system in the ccRCC TIME is crucial for developing effective immunotherapies to treat this disease.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/metabolism , CD8-Positive T-Lymphocytes , T-Lymphocytes, Regulatory , Cytokines , Tumor Microenvironment
2.
Odovtos (En línea) ; 24(3)dic. 2022.
Article in English | LILACS, SaludCR | ID: biblio-1406148

ABSTRACT

Abstract Bruxism is the repetitive muscle-mandibular behavior characterized by clenching and/or grinding of the teeth, which reflects the presence of one or more underlying conditions or factors. The objective of this descriptive study was to determine the association between bruxism and stress self-perceived during the pandemic, as well as their frequency by gender and academic area. An interrogation and self-perceived stress scale PSS-14 were applied to students from the different areas of the Institute of Health Sciences (ICSa) to determine the presence or absence of stress and bruxism symptom, a Chi-square was used for the comparison between variables, considering a value of p0.005. ICSa students between 18 and 24 age perceive symptoms of bruxism and high levels of stress caused during the pandemic.


Resumen El bruxismo es el comportamiento músculo-mandibular repetitivo caracterizado por apretamiento y/o rechinamiento de los dientes, que refleja la presencia de una o varias condiciones o factores subyacentes. Se realizó un estudio descriptivo con el objetivo de determinar la asociación del nivel de estrés y síntomas de bruxismo autopercibidos durante la pandemia, así como su frecuencia por género y área académica. Se aplicó un interrogatorio y escala de estrés percibido PSS-14 a los estudiantes de las distintas áreas del Instituto de Ciencias de la Salud (ICSa) para determinar la presencia o ausencia de estrés y síntomas de bruxismo, se utilizó una Chi-cuadrada para la comparación entre variables, considerando significativo un valor de p0.0001. Los estudiantes de 18 a 24 años de edad del ICSa perciben síntomas de bruxismo y altos niveles de estrés originados durante la pandemia.


Subject(s)
Humans , Male , Female , Adult , Students, Medical , Dental Stress Analysis , COVID-19 , Bruxism , Mexico
3.
J Exp Clin Cancer Res ; 39(1): 33, 2020 Feb 10.
Article in English | MEDLINE | ID: mdl-32041631

ABSTRACT

BACKGROUND: Renal cell carcinoma (RCC) is a highly vascular tumor and patients with low risk metastatic RCC of clear-cell histological sub-type (mccRCC) are treated with tyrosine-kinase inhibitors (TKIs), sunitinib, as the first-line of treatment. Unfortunately, TKI resistance eventually develops, and the underlying molecular mechanism is not well understood. METHODS: RCC cell-line with metastatic clear-cell histology (Caki-1), and patient samples were analysed to identify the role of Y-box binding protein 1 (YB-1) and ATP-binding cassette sub-family B member 1 (ABCB-1) in acquired sunitinib-resistance development. Caki-1 was conditioned with increasing sunitinib doses to recapitulate acquired resistance development in clinics. Sunitinib-conditioned and wild-type Caki-1 were subjected to cell viability assay, scratch assay, chicken embryo chorioallantoic membrane engraftment and proteomics analysis. Classical biochemical assays like flow cytometry, immunofluorescent staining, immunohistochemical staining, optical coherence tomography imaging, Western Blot and RT-PCR assays were applied to determine the possible mechanism of sunitinib-resistance development and the effect of drug treatments. Publicly available data was also used to determine the role of YB-1 upregulation in ccRCC and the patients' overall survival. RESULTS: We demonstrate that YB-1 and ABCB-1 are upregulated in sunitinib-resistant in vitro, ex vivo, in vivo and patient samples compared to the sensitive samples. This provides evidence to a mechanism of acquired sunitinib-resistance development in mccRCC. Furthermore, our results establish that inhibiting ABCB-1 with elacridar, in addition to sunitinib, has a positive impact on reverting sunitinib-resistance development in in vitro, ex vivo and in vivo models. CONCLUSION: This work proposes a targeted therapy (elacridar and sunitinib) to re-sensitize sunitinib-resistant mccRCC and, possibly, slow disease progression.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Drug Resistance, Neoplasm/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Y-Box-Binding Protein 1/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Animals , Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Disease Models, Animal , Female , Humans , Immunohistochemistry , Kidney Neoplasms/drug therapy , Kidney Neoplasms/metabolism , Male , Mice , Models, Biological , Neoplasm Metastasis , Neoplasm Staging , Phenotype , Sunitinib/pharmacology , Sunitinib/therapeutic use , Treatment Outcome , Xenograft Model Antitumor Assays , Y-Box-Binding Protein 1/metabolism
4.
Sci Rep ; 10(1): 2026, 2020 02 06.
Article in English | MEDLINE | ID: mdl-32029828

ABSTRACT

Clear-cell renal cell carcinoma (ccRCC) is a common therapy resistant disease with aberrant angiogenic and immunosuppressive features. Patients with metastatic disease are treated with targeted therapies based on clinical features: low-risk patients are usually treated with anti-angiogenic drugs and intermediate/high-risk patients with immune therapy. However, there are no biomarkers available to guide treatment choice for these patients. A recently published phase II clinical trial observed a correlation between ccRCC patients' clustering and their response to targeted therapy. However, the clustering of these groups was not distinct. Here, we analyzed the gene expression profile of 469 ccRCC patients, using featured selection technique, and have developed a refined 66-gene signature for improved sub-classification of patients. Moreover, we have identified a novel comprehensive expression profile to distinguish between migratory stromal and immune cells. Furthermore, the proposed 66-gene signature was validated using a different cohort of 64 ccRCC patients. These findings are foundational for the development of reliable biomarkers that may guide treatment decision-making and improve therapy response in ccRCC patients.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor/genetics , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Precision Medicine/methods , Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents, Immunological/pharmacology , Biomarkers, Tumor/antagonists & inhibitors , Carcinoma, Renal Cell/genetics , Clinical Decision-Making/methods , Cluster Analysis , Cohort Studies , Datasets as Topic , Feasibility Studies , Female , Gene Expression Profiling , Humans , Kidney Neoplasms/genetics , Male , Medical Oncology/methods , Middle Aged , Patient Selection , Prognosis , Transcriptome/genetics
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