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1.
J Clin Med ; 12(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615183

RESUMO

PURPOSE: To explore the tumor proteome of patients diagnosed with localized clear cell renal cancer (ccRCC) and treated with surgery. MATERIAL AND METHODS: A total of 165 FFPE tumor samples from patients diagnosed with ccRCC were analyzed using DIA-proteomics. Proteomics ccRCC subtypes were defined using a consensus cluster algorithm (CCA) and characterized by a functional approach using probabilistic graphical models and survival analyses. RESULTS: We identified and quantified 3091 proteins, including 2026 high-confidence proteins. Two proteomics subtypes of ccRCC (CC1 and CC2) were identified by CC using the high-confidence proteins only. Characterization of molecular differences between CC1 and CC2 was performed in two steps. First, we defined 514 proteins showing differential expression between the two subtypes using a significance analysis of microarrays analysis. Proteins overexpressed in CC1 were mainly related to translation and ribosome, while proteins overexpressed in CC2 were mainly related to focal adhesion and membrane. Second, a functional analysis using probabilistic graphical models was performed. CC1 subtype is characterized by an increased expression of proteins related to glycolysis, mitochondria, translation, adhesion proteins related to cytoskeleton and actin, nucleosome, and spliceosome, while CC2 subtype showed higher expression of proteins involved in focal adhesion, extracellular matrix, and collagen organization. CONCLUSIONS: ccRCC tumors can be classified in two different proteomics subtypes. CC1 and CC2 present specific proteomics profiles, reflecting alterations of different molecular pathways in each subtype. The knowledge generated in this type of studies could help in the development of new drugs targeting subtype-specific deregulated pathways.

2.
Clin. transl. oncol. (Print) ; 24(11): 2055-2063, noviembre 2022.
Artigo em Inglês | IBECS | ID: ibc-210134

RESUMO

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer. (AU)


Assuntos
Humanos , Carcinoma de Células Renais , Neoplasias Renais/genética , MicroRNAs/genética , RNA Mensageiro/genética , Carcinoma
3.
Clin Transl Oncol ; 24(11): 2055-2063, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35729452

RESUMO

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , MicroRNAs/genética , RNA Mensageiro/genética
4.
Allergol. immunopatol ; 47(3): 303-308, mayo-jun. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-186494

RESUMO

Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs). IRAEs, ranging from mild to potentially life-threatening events, can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil, usually result in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker, would not allow clinicians select or exclude patients for treatment with checkpoint inhibitors


No dipsonible


Assuntos
Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Ipilimumab/uso terapêutico , Neoplasias/terapia , Nivolumabe/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antígeno HLA-B7/imunologia , Antígeno CTLA-4/imunologia , Sistema Imunitário/efeitos dos fármacos , Ipilimumab/efeitos adversos , Neoplasias/imunologia , Neoplasias/mortalidade , Receptor de Morte Celular Programada 1/imunologia
5.
Allergol Immunopathol (Madr) ; 47(3): 303-308, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29983240

RESUMO

Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs). IRAEs, ranging from mild to potentially life-threatening events, can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil, usually result in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker, would not allow clinicians select or exclude patients for treatment with checkpoint inhibitors.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Ipilimumab/uso terapêutico , Neoplasias/terapia , Nivolumabe/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/imunologia , Antígeno CTLA-4/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Ipilimumab/efeitos adversos , Neoplasias/imunologia , Neoplasias/mortalidade , Nivolumabe/efeitos adversos , Seleção de Pacientes , Receptor de Morte Celular Programada 1/imunologia , Análise de Sobrevida
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