RESUMO
Peptides have potential bioactive functions, and the peptidomics landscape has been broadly investigated for various diseases, including cancer. In this chapter, we reviewed the past four years of literature available and selected 16 peer-reviewed publications exploring peptidomics in diagnosis, prognosis, and treatment in cancer research. We highlighted their main aims, mass spectrometry-based peptidomics, multi-omics, data-driven and in silico strategies, functional assays, and clinical applications. Moreover, we underscored several levels of difficulties in translating the peptidomics findings to clinical practice, aiming to learn with the accumulated knowledge and guide upcoming studies. Finally, this review reinforces the peptidomics robustness in discovering potential candidates for monitoring the several stages of cancer disease and therapeutic treatment, leveraging the management of cancer patients in the future.
Assuntos
Neoplasias , Proteômica , Humanos , Peptídeos/uso terapêutico , Espectrometria de Massas , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMO
Cancer is a significant cause of death, precluding increasing life expectancy worldwide. That is a multifactorial disease initiated by intrinsic or extrinsic factors that induce cell differentiation into cancer cells. However, cancer development, progression, and metastasis are not controlled only by cancer cells. The entire environment around these cells, named tumor microenvironment (TME), influences tumor development and spread. The tumor microenvironment is formed by cancer cells and heterogenous nonmalignant cells integrated with a complex extracellular matrix. The main cellular components of the TME are cancer-associated fibroblasts (CAFs), T lymphocytes, B cells, tumor-associated macrophages (TAMs), dendritic cells (DC), natural killer (NK) cells, tumor-associated neutrophils (TANs), Stem Cells, Endothelial Cells and their soluble secreted extracellular vesicles (EVs) that modulate cancer cells to establish and disseminate. This review provides a recent insight into the role of EVs secreted from different populations of the TME associated with the initiation and progression of carcinoma.
Assuntos
Fibroblastos Associados a Câncer , Carcinoma , Vesículas Extracelulares , Humanos , Microambiente Tumoral , Células Endoteliais , Linfócitos BRESUMO
The search for biomarkers associated with oral leukoplakia malignant transformation is critical for early diagnosis and improved prognosis of oral cancer patients. This systematic review and meta-analysis aimed to assess protein-based markers potentially associated with malignant transformation of oral leukoplakia. Five database and the grey literature were searched. In total, 142 studies were included for qualitative synthesis, where 173 proteins were investigated due to their potential role in malignant progression from oral leukoplakia (OL) to oral squamous cell carcinoma (OSCC). The abundance of these proteins was analyzed in fixed tissues and/or biofluid samples, mainly by immunohistochemistry and ELISA, and 12 were shared by both samples. Enrichment analysis revealed that the differential abundant proteins are mostly involved with regulation of cell death, regulation of cell proliferation, and regulation of apoptotic process. Also, these proteins are mainly expressed in the extracellular region (55.5%), cell surface (24.8%), and vesicles (49.1%). The meta-analysis revealed that the proteins related to tumor progression, PD-L1, Mdm2, and Mucin-4 were significantly associated with greater abundance in OSCC patients, with an Odds Ratio (OR) of 0.12 (95% CI: 0.04-0.40), 0.44 (95% CI: 0.24-0.81), and 0.18 (95% CI: 0.04-0.86), respectively, with a moderate certainty of evidence. The results indicate a set of proteins that have been investigated across OSCC initiation and progression, and whose transcriptional expression is associated with clinical characteristics relevant to the prognosis and aggressiveness. Further verification and validation of this biomarkers set are strongly recommended for future clinical application.
RESUMO
The poor prognosis of head and neck cancer (HNC) is associated with metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision-making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identify nodal metastasis signatures in blood and saliva. We present a proteomic characterization wiring multiple sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.
Assuntos
Neoplasias de Cabeça e Pescoço , Proteoma , Humanos , Metástase Linfática/patologia , Proteômica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Microambiente TumoralRESUMO
Protease activity has been associated with pathological processes that can lead to cancer development and progression. However, understanding the pathological unbalance in proteolysis is challenging because changes can occur simultaneously at protease, their inhibitor, and substrate levels. Here, we present a pipeline that combines peptidomics, proteomics, and peptidase predictions for studying proteolytic events in the saliva of 79 patients and their association with oral squamous cell carcinoma (OSCC) prognosis. Our findings revealed differences in the saliva peptidome of patients with (pN+) or without (pN0) lymph-node metastasis and delivered a panel of ten endogenous peptides correlated with poor prognostic factors plus five molecules able to classify pN0 and pN+ patients (area under the receiver operating characteristic curve > 0.85). In addition, endopeptidases and exopeptidases putatively implicated in the processing of differential peptides were investigated using cancer tissue gene expression data from public repositories, reinforcing their association with poorer survival rates and prognosis in oral cancer. The dynamics of the OSCC-related proteolysis were further explored via the proteomic profiling of saliva. This revealed that peptidase/endopeptidase inhibitors exhibited reduced levels in the saliva of pN+ patients, as confirmed by selected reaction monitoring-mass spectrometry, while minor changes were detected in the level of saliva proteases. Taken together, our results indicated that proteolytic activity is accentuated in the saliva of patients with OSCC and lymph-node metastasis and, at least in part, is modulated by reduced levels of salivary peptidase inhibitors. Therefore, this integrated pipeline provided better comprehension and discovery of molecular features with implications in the oral cancer metastasis prognosis.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Metástase Linfática , Neoplasias Bucais/metabolismo , Peptídeo Hidrolases/metabolismo , Peptídeos/análise , Saliva/química , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Bucais/patologia , Peptídeos/metabolismo , Prognóstico , ProteômicaRESUMO
AIMS: Evaluate the abundance of the selected targets, alpha-1-antitrypsin (A1AT) and macrophage migration inhibitory factor (MIF), and correlate these findings with the risk of developing severe oral mucositis (OM). MATERIALS AND METHODS: Head and neck squamous cell carcinoma (HNSCC) patients submitted to radiotherapy (RT) or chemoradiotherapy (CRT) were assessed. OM grade and pain were evaluated daily during treatment. Two protein targets, A1AT and MIF, were evaluated, using selected reaction monitoring-mass spectrometry (SRM-MS), in whole saliva, collected prior to oncologic treatment. The results obtained from the targeted proteomic analysis were correlated with OM clinical outcomes. RESULTS: A total of 27 patients were included, of whom 21 (77.8%) had locally advanced disease (clinical stage III or IV). Most patients (70.4%) received CRT. OM grades 2 (40.8%) and 3 (33.3%) were the most prevalent during RT with a mean highest reported OM-related pain of 3.22 through the visual analogue scale (VAS). The abundance of A1AT and MIF correlated significantly with severe (grades 3 or 4, p < 0.02) compared with moderate-low (grades 1 or 2, p < 0.04) OM grade. CONCLUSIONS: There is a correlation between the abundance of salivary A1AT and MIF and oncologic treatment-induced OM. The correlation of MIF expression with severe OM appears to be compatible with its physiological pro-inflammatory role. These results open up great possibilities for the use of salivary MIF and A1AT levels as prognostic markers for effective therapeutic interventions, such as photobiomodulation therapy, patient-controlled analgesia, or personalized medicaments.
Assuntos
Biomarcadores/metabolismo , Neoplasias de Cabeça e Pescoço/complicações , Fatores Inibidores da Migração de Macrófagos/metabolismo , Qualidade de Vida/psicologia , Saliva/metabolismo , Estomatite/induzido quimicamente , alfa 1-Antitripsina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
Different regions of oral squamous cell carcinoma (OSCC) have particular histopathological and molecular characteristics limiting the standard tumor-node-metastasis prognosis classification. Therefore, defining biological signatures that allow assessing the prognostic outcomes for OSCC patients would be of great clinical significance. Using histopathology-guided discovery proteomics, we analyze neoplastic islands and stroma from the invasive tumor front (ITF) and inner tumor to identify differentially expressed proteins. Potential signature proteins are prioritized and further investigated by immunohistochemistry (IHC) and targeted proteomics. IHC indicates low expression of cystatin-B in neoplastic islands from the ITF as an independent marker for local recurrence. Targeted proteomics analysis of the prioritized proteins in saliva, combined with machine-learning methods, highlights a peptide-based signature as the most powerful predictor to distinguish patients with and without lymph node metastasis. In summary, we identify a robust signature, which may enhance prognostic decisions in OSCC and better guide treatment to reduce tumor recurrence or lymph node metastasis.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/mortalidade , Neoplasias Bucais/mortalidade , Recidiva Local de Neoplasia/diagnóstico , Proteômica/métodos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Tomada de Decisão Clínica , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Metástase Linfática , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/prevenção & controle , Peptídeos/análise , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Saliva/química , Taxa de SobrevidaRESUMO
INTRODUCTION: Smoking is considered a public health problem and in many cases is responsible for the development of lung diseases and cancer. One of the mechanisms by which tobacco can induce cancer is through the generation of free radicals, establishing an oxidative stress status in smokers. With increasing smoking among women, much evidence in the literature has shown a relation between smoking and breast cancer development. OBJECTIVE: The aim of this review was to analyze the available studies in literature that demonstrate the association between smoking and the risk of breast cancer development. METHODS: We performed a review from the literature based on the search results in PubMed and Scielo. The selected works were composed by current articles according to their relevance and human application. RESULTS: The literature revealed several published studies linking smoking to oxidative stress through the action of free radicals that are generated by toxic compounds found in cigarettes. There are few studies relating smoking with breast cancer, which is a relatively more recent research line, where the vast majority of works includes epidemiological and controversial studies. CONCLUSIONS: The selected works show that, although controversial, smoking is considered a risk factor for developing breast cancer.
Assuntos
Humanos , Estresse Fisiológico , Fatores de Risco , Neoplasias da Mama , NicotianaRESUMO
OBJECTIVE: This study aimed to describe the main toxic effects mediated by oxidative stress associated with treatment with doxorubicin in scientific research articles available in the literature. MATERIAL AND METHODS: This study employed a descriptive review methodology applied to the literature. For the theoretical scientific background, we used the electronic PubMed search engines. CONCLUSION: The toxicity of chemotherapy treatment with doxorubicin causes damage in various organs of patients who are in uninterrupted treatment with this antineoplastic agent. Anthracycline-induced cardiotoxicity has been investigated to a great degree and is especially indicated as the principal side effect. Therefore, care needs to be given to other damage caused by this medication as important as myocardial toxicity, such as renal, pulmonary and liver toxicity, among others. There is a need for further studies to prevent or even encounter a way to control the damage caused by these toxicities in various tissues.
Assuntos
Humanos , Estresse Fisiológico , Tratamento Farmacológico , ToxicidadeRESUMO
Candida albicans pode causar graves infecções em pacientes que estão imunocomprometidos por doenças, por cirurgias ou por terapia imunossupressiva. Os altos níveis de morbidade e mortalidade resultantes de infecções em pacientes hospitalizados mostraram que C. albicans tornou-se um patógeno humano de grande relevância clínica. Mesmo o sistema imune sendo o principal fator que define a transição do fungo de comensal para patogênico, fatores de virulência expressos por C. albicans, tais como adesinas, mudança fenotípica, comportamento dimórfico, e secreção de enzimas hidrolíticas, podem contribuir para a persistência da colonização, assim como o desenvolvimento de episódios sintomáticos. A defesa do hospedeiro compreende ingestão e eliminação do fungo por células fagocíticas que possuem vários receptores, como o Toll-4, dectina-1 associado a receptores tipo Toll-2 e receptores de manose. A interleucina-10 (IL-10) produzida por fagócitos determina a susceptibilidade do hospedeiro a infecção fúngica, enquanto a IL-10 produzida por células T reguladoras é responsável pelo comensalismo. Em contraste, a produção de fator de necrose tumoral- α (TNF-α), interleucina 1 β (lL-1 β), (IL-6), (Il-12) e IL-17 conferem imunidade protetora. O interferon-γ (IFN- γ) produzido por células natural killer e células Th1 estimula a migração de fagócitos e maior eficácia na destruição do fungo. Nas células epiteliais de mucosas os receptores NOD-like e defensinas-β citoplasmáticos evitam a translocação de C. albicans da microbiota para os tecidos os quais são modulados por citocinas IL-1 β,IL-17 e IL-22.
Candida albicans can cause grave infections in patients who are immunocompromised by diseases, by surgery, or by immunesupresive therapy. The high levels of morbidity and mortality resulting from those infections in hospitalized patients show that C. albicans became a prominent human pathogen. Although the host immune system is the major factor balancing the transition from commensalisms to pathogenicity, several virulence attributes expressed by C. albicans, such as adhesion factors, phenotypic switching, dimorphic behavior, and secretion of hydrolytic enzymes, might contribute to the persistence of colonization as well as the development of symptomatic episodes. Host defense against candidiasis relies mainly on the ingestion and elimination of C. albicans by phagocytic cells, which present receptors Toll-like 4, dectin1 associated to receptors Toll-like2 and mannose receptors. The cytokine IL-10 (IL-10) produced by phagocytes has a crucial role on susceptibility of host fungal infection, whereas IL-10 produced by regulatory T cells is mainly responsible by commensalisms. In contrast, productions of tumour necrosis factor - α (TNF-α), interleukin1 β (lL-1 β), (IL-6) and (Il-12) provided protective cellmediated immunity. The interferon-γ produced by natural killer and TH1 cells stimulates migration of phagocytes and major efficacy on destruction of fungi. In epithelial cells from mucosas the NOD-like receptors and defensins-β cytoplasmatic prevent the translocation of C. albicans from microbiota to tissues, which are modulated by IL-1 β, Il-17 and Il-22 cytokines.
Assuntos
Candida albicans , Células Th1RESUMO
Objective: This revision characterizes the biomarkers used for analysis of the development of oxidative stress produced during breast cancer chemotherapy. Materials and methods: A search of articles indexed in digital databases (Lilacs, Bireme, PubMed, Scielo and digital libraries), along with publications printed as books, periodicals and articles not available online, in the period from 1979 to 2009. Conclusion: Reactive oxygen and nitrogen species are produced, principally, during aerobic metabolism; however, its synthesis can be exacerbated or antioxidant defense reduced or more usually, both conditions can occurr in many pathophysiologic situations, leading to a net reactive species yelded. This unbalance is defined as oxidative stress. Stress biomarkers can be defined as predictive indicators able to detect in vivo oxidative damage and can be subdivided into antioxidant and pro-oxidants. To verify the antioxidant system, it is possible to analyze the superoxide dismutase enzymes, catalase and glutathione, along with vitamins A, E, C and glutathione among others. The analysis of pro-oxidants can be made through the verification of protein nitration and oxidation, heat shock proteins, lipoperoxidation, formation of aldehydes for malondialdehyde tests, 4-hydroxynonenal, oxidized LDL and isoprostanes or for chemiluminescent techniques. Advances in cancer detection through the identification of potential biomarkers consist of a promising strategy for the prevention and early identification of this pathology.
Assuntos
Humanos , Antioxidantes , Biomarcadores Farmacológicos , Neoplasias da Mama , Radicais Livres , Neoplasias , Estresse Oxidativo , Catalase , Tratamento Farmacológico , Glutationa , Literatura de Revisão como AssuntoRESUMO
TEMA: a Reabilitação Vestibular constitui-se numa opção de tratamento para pacientes portadores de síndrome vestibular periférica e cefaleia. PROCEDIMENTOS: o paciente, do sexo feminino com 26 anos de idade apresentava síndrome vestibular periférica acompanhada de crises de cefaleia. Foi realizada avaliação e terapia fonoaudiológica com exercícios de habituação vestibular além de fisioterapia e dieta recomendada pelo nutricionista. RESULTADOS: no período de 3 meses com reabilitação vestibular realizada semanalmente observou-se melhora no quadro vertiginoso e da cefaleia da paciente. CONCLUSÕES: evidenciou-se boa eficácia clínica para o tratamento desta paciente através da reabilitação vestibular com exercícios de habituação vestibular. Salienta-se a eficácia da reabilitação para a melhora na qualidade de vida da paciente e minimização das crises de cefaleia.
BACKGROUND: vestibular rehabilitation is an option for treating peripheral vestibular syndrome and headache patients. PROCEDURES: the patient is a 29-year old woman and has Peripheral Vestibular Syndrome along with headache attacks. Evaluation and Phonoaudiological therapy with exercises of habituation tests with physical and nutritional therapy were carried out. RESULTS: in 3 month period with weekly vestibular rehabilitation therapy, we observed an improvement in the condition of the patient's vertigo and migraine. CONCLUSIONS: it was evident that the patient's treatment through the rehabilitation test with habituation test exercises had good efficiency. Please note the effectiveness of the rehabilitation for the improvement in the patient's life quality and minimization of headache attacks.