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1.
Int J Mol Sci ; 25(14)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39062875

RESUMO

Burns generate every year an important burden of morbidity, being a major global public health problem through prolonged hospitalization, complications, and increased mortality. This study's purpose was to evaluate the serum levels of three adipokines and to establish significant correlations with other circulating molecules and with some clinical parameters. We evaluated 32 children with severe burns (over 25% total burned surface area-TBSA) at 48 h, day 10, and day 21 post burn, and 21 controls. The serum levels of adiponectin, resistin, leptin, tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein (CRP) (among nine other biochemical parameters) were detected by Multiplex technique. Significant statistical differences were obtained for resistin and leptin compared to the control group, in different moments of measurements. Adiponectin serum levels presented statistically significant correlations with hot liquid mechanism of burn, the Revised Baux score, TBSA, resistin, PAI-1, CRP, TNF-α, and triglycerides (TGLs) serum levels. Resistin serum levels presented statistically significant correlations with adiponectin, CRP, PAI-1, leptin, and TNF-α. Additionally, we found statistically significant correlations between leptin serum levels and length of hospitalization, TNF-α, resistin, adiponectin, and PAI-1 serum levels. In severely burned children, adiponectin, resistin, and leptin specifically correlate with clinical parameters and with proteins involved in the systemic inflammatory response and the hypermetabolic response.


Assuntos
Adipocinas , Queimaduras , Proteína C-Reativa , Leptina , Humanos , Queimaduras/sangue , Masculino , Feminino , Criança , Estudos Prospectivos , Adipocinas/sangue , Leptina/sangue , Proteína C-Reativa/metabolismo , Resistina/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Fator de Necrose Tumoral alfa/sangue , Pré-Escolar , Biomarcadores/sangue , Adiponectina/sangue , Adolescente
2.
Healthcare (Basel) ; 12(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38610182

RESUMO

Patient Blood Management (PBM) as a multidisciplinary practice and a standard of care for the anemic surgical patient is playing an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. The success of PBM implementation depends on staff awareness and involvement in this approach. The main objective of our study was to explore physicians' perceptions of the conditions for implementing PBM in hospitals and the main obstacles they face in detecting and treating anemic patients undergoing elective surgery. This cross-sectional descriptive study includes 113 Romanian health units, representing 23% of health units with surgical wards nationwide. A 12-item questionnaire was distributed to the participants in electronic format. A total of 413 questionnaires representing the perceptions of 347 surgeons and 66 anesthesia and intensive-care specialists were analyzed. Although a lack of human resources was indicated by 23.70% of respondents as the main reason for not adhering the guidelines, the receptiveness of medical staff to implementing the PBM standard was almost 90%. In order to increase adherence to the standard, additional involvement of anesthesia and intensive-care physicians would be necessary from the perception of 35.70% of the responders: 23.60% of surgeons and 18.40% of hematologists.

3.
Rom J Intern Med ; 62(2): 203-209, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38377067

RESUMO

Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity. Methods. Eighty-five type 2 diabetes, aged 40-70 years with a duration of diabetes less than 6 years without infections, epilepsy, chronic liver or cardiac diseases, without alcohol consumption (>20 g/day) were divided in two subgroups, those with normal and those with high abnormal GGT. Results. The diabetic patients with high GGT (n=31) had dysglycaemia, dyslipidemia, higher inflammatory markers (CRP, TNF-α, MCP-1) and endothelial dysfunction (high leptin and sICAM). sICAM, serum MCP-1 and TNF-α levels had significant correlations with GGT activity (r= 0.38, r=0.30 and 0.26 respectively, p<0.05). Conclusion. This study underlines that in non-alcoholic diabetic patients, with a duration of the metabolic disease less than 6 years, sICAM, serum MCP-1 and TNF-α might play an important role in dysmetabolism, and higher level for GGT represents the "red flag" for this condition.


Assuntos
Diabetes Mellitus Tipo 2 , gama-Glutamiltransferase , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Quimiocina CCL2/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Dislipidemias/sangue , Dislipidemias/complicações , gama-Glutamiltransferase/sangue , Molécula 1 de Adesão Intercelular/sangue , Leptina/sangue , Fator de Necrose Tumoral alfa/sangue
4.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38339127

RESUMO

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Neoplasias Gástricas , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Sirolimo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/metabolismo , Sistema de Sinalização das MAP Quinases
5.
Healthcare (Basel) ; 11(16)2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37628431

RESUMO

(1) Background: Patient blood management (PBM) program as a multidisciplinary practice and a standard of care for the anemic surgical patient has an increasingly important role in reducing transfusions and optimizing both clinical outcomes and costs. Documented success of PBM implementation is not sufficient for implementation of recommendations and correct use at hospital level. The primary objective of our study was to define a composite patient blood management process safety index-Safety Index in PBM (SIPBM)-that measures the impact of screening and treating anemic patients on the efficiency and effectiveness of the patient care process undergoing elective surgery. (2) Methods: We conducted a retrospective comparative study in a tertiary hospital by collecting data and analyzing the Safety Index in PBM (SIPBM) in patients undergoing major elective surgical procedures. (3) Results: The percentage of patients from the total of 354 patients (178 in 2019 and 176 in 2022) included in the study who benefited from preoperative iron treatment increased in 2022 compared to 2019 from 27.40% to 36.71%. The median value of the SIPBM was 1.00 in both periods analyzed, although there is a significant difference between the two periods (p < 0.005), in favor of 2022. (4) Conclusions: Measuring the effectiveness of PBM implementation and providing ongoing feedback through the Safety Index in PBM (SIPBM) increases the degree to which opportunities to improve the PBM process are identified. The study represents a first step for future actions and baselines to develop tools to measure the safety and impact of the patient blood management process in the surgical field.

6.
Int J Mol Sci ; 24(9)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37176098

RESUMO

Renal cell carcinoma (RCC) represents 85-95% of kidney cancers and is the most frequent type of renal cancer in adult patients. It accounts for 3% of all cancer cases and is in 7th place among the most frequent histological types of cancer. Clear cell renal cell carcinoma (ccRCC), accounts for 75% of RCCs and has the most kidney cancer-related deaths. One-third of the patients with ccRCC develop metastases. Renal cancer presents cellular alterations in sugars, lipids, amino acids, and nucleic acid metabolism. RCC is characterized by several metabolic dysregulations including oxygen sensing (VHL/HIF pathway), glucose transporters (GLUT 1 and GLUT 4) energy sensing, and energy nutrient sensing cascade. Metabolic reprogramming represents an important characteristic of the cancer cells to survive in nutrient and oxygen-deprived environments, to proliferate and metastasize in different body sites. The phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K/AKT/mTOR) signaling pathway is usually dysregulated in various cancer types including renal cancer. This molecular pathway is frequently correlated with tumor growth and survival. The main aim of this review is to present renal cancer types, dysregulation of PI3K/AKT/mTOR signaling pathway members, crosstalk with VHL/HIF axis, and carbohydrates, lipids, and amino acid alterations.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/metabolismo , Lipídeos , Redes e Vias Metabólicas , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Fator 1 Induzível por Hipóxia
7.
J Clin Med ; 13(1)2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-38202227

RESUMO

This case report delves into the intricacies of a challenging clinical scenario involving deep pelvic endometriosis, which manifested with renal complications. Endometriosis, a complex gynecological condition, is explored in this case, highlighting its multifaceted nature. The patient presented with a complex interplay of symptoms, including chronic pelvic pain, urinary tract issues, and severe deep adenomyosis. The diagnostic journey was protracted, emphasizing the need for early recognition and intervention in such cases. A thorough evaluation, including laparoscopic examination and histopathological analysis, revealed the extensive presence of endometriotic lesions in various pelvic and renal structures, ultimately leading to left hydronephrosis. The report underscores the significance of timely diagnosis and surgical intervention to prevent irreversible renal damage. This case provides valuable insights into the management of deep endometriosis with renal involvement and the importance of interdisciplinary collaboration. Understanding the complexities of this condition can aid in improving patient outcomes and enhancing the quality of care provided.

8.
Int J Mol Sci ; 23(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36077529

RESUMO

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies.


Assuntos
Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Proliferação de Células , Humanos , Neoplasias Pancreáticas/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Microambiente Tumoral , Neoplasias Pancreáticas
9.
Int J Mol Sci ; 23(5)2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35269613

RESUMO

O2 deprivation induces stress in living cells linked to free-radical accumulation and oxidative stress (OS) development. Hypoxia is established when the overall oxygen pressure is less than 40 mmHg in cells or tissues. However, tissues and cells have different degrees of hypoxia. Hypoxia or low O2 tension may be present in both physiological (during embryonic development) and pathological circumstances (ischemia, wound healing, and cancer). Meanwhile, the kidneys are major energy-consuming organs, being second only to the heart, with an increased mitochondrial content and O2 consumption. Furthermore, hypoxia-inducible factors (HIFs) are the key players that orchestrate the mammalian response to hypoxia. HIFs adapt cells to low oxygen concentrations by regulating transcriptional programs involved in erythropoiesis, angiogenesis, and metabolism. On the other hand, one of the life-threatening complications of severe burns is acute kidney injury (AKI). The dreaded functional consequence of AKI is an acute decline in renal function. Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of HIFs in the development of AKI in patients with severe burns, because kidney hypoxia is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia.


Assuntos
Injúria Renal Aguda , Queimaduras , Injúria Renal Aguda/metabolismo , Animais , Queimaduras/patologia , Humanos , Hipóxia/metabolismo , Rim/metabolismo , Mamíferos/metabolismo , Oxigênio/metabolismo
10.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638601

RESUMO

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/fisiologia , Animais , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Exp Ther Med ; 22(2): 877, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34194555

RESUMO

Oral cancer represents one of the most common types of cancer worldwide, with oral squamous cell carcinoma (OSCC) being the most frequently diagnosed. Cytokines play a crucial role in inflammation, apoptosis and metastasis. Interleukin (IL)-8 promotes the direct migration of inflammatory cells. IL-6 induces tumor cell proliferation, increases expression of invasiveness and angiogenetic factors or matrix metalloproteinases (MMPs), promoting metastasis. Tissue inhibitor of metalloproteinases (TIMPs) blocks the action of MMPs controlling extracellular matrix degradation and inhibiting metastasis. The aim of our study was to analyze the existence of correlations between inflammation markers (IL-6 and IL-8) and extracellular degradation protection markers such as TIMP-1 in OSCC tumors. Our study included 20 patients (12 females and 8 males) diagnosed with OSCC, recruited from January to April, 2020. IL-8, IL-6 and TIMP-1 levels were measured in the tumor cell lysates by ELISA technique, using relevant assay kits. Our results showed a positive and significant correlation between IL-6 and IL-8 (P=0.005, R=0.517) indicating that high IL-8 levels can be associated with high IL-6 levels. We also found a significant and high negative correlation (P<0.001, R=-0.673) between IL-6 and TIMP-1 and a significant and high negative correlation (P<0.001, R=-0.684) between IL-8 and TIMP-1 indicating that high levels of IL-8 and IL-6 are significantly associated with lower levels of TIMP-1. In conclusion, our study confirms the available literature data on IL-6 and IL-8 as potential markers for oral cancers such as OSCC and affect the tumor microenvironment by decreasing TIMPs. All three biomarkers included in this study have the potential to be used as detection or prognostic factors for oral cancer.

12.
Materials (Basel) ; 14(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072756

RESUMO

Carotenoids loaded in nanoparticles should be regarded as a promising way to increase the availability in healthy cells and to induce apoptosis in cancer. Lutein is a carotenoid that, in contrast to beta-carotene, has no known toxicities. Oral cancer represents one of the most frequent types of cancer world-wide with an incidence rate of about 9% of all types of cancer. Almost 95% of all oral cancers are represented by squamous cell carcinomas (OSCC). The aim of this study was to review and analyse the effects of lutein and Poly(d,l-lactide-co-glycolide) (PLGA) Nps containing lutein (Lut Nps) on oxidative stress biomarkers (OXSR-1, FOXO-3, TAC) and collagen degradation biomarker-MMP-9, in human cells BICR10 of buccal mucosa squamous carcinoma. Lut Nps were prepared by the emulsion-solvent evaporation method. MMP, OXSR-1, TAC, FOXO-3 and MMP-9 were measured in tumour cell lysates by the ELISA technique. Our results have shown that in Lut 100 cells and Lut Nps the OXSR1 (p < 0.001, p < 0.001) and TAC (p < 0.001, p < 0.001) values were significantly higher than in control cells. The Lut 100 and Lut Nps FOXO-3 levels revealed no significant differences versus the control. MMP-9 levels were significantly reduced (p < 0.001) in the Lut Nps cells versus control cells. In our study conditions, lutein and lutein Nps did not trigger an oxidative stress by ROS induction. However, lutein Nps treatment seemed to have a positive effect, by downregulating the MMP-9 levels. Loaded in Nps, lutein could be regarded as a protective factor against local invasiveness, in whose molecular landscape MMPs, and especially MMP-9 are the main actors.

13.
Int J Mol Sci ; 22(1)2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33375317

RESUMO

Breast cancer is a serious health problem worldwide, representing the second cause of death through malignancies among women in developed countries. Population, endogenous and exogenous hormones, and physiological, genetic and breast-related factors are involved in breast cancer pathogenesis. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is a signaling pathway involved in cell proliferation, survival, invasion, migration, apoptosis, glucose metabolism and DNA repair. In breast tumors, PIK3CA somatic mutations have been reported, located in exon 9 and exon 20. Up to 40% of PIK3CA mutations are estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) -negative in primary and metastatic breast cancer. HER2 is overexpressed in 20-30% of breast cancers. HER1, HER2, HER3 and HER4 are membrane receptor tyrosine kinases involved in HER signaling to which various ligands can be attached, leading to PI3K/AKT activation. Currently, clinical studies evaluate inhibitors of the PI3K/AKT/mTOR axis. The main purpose of this review is to present general aspects of breast cancer, the components of the AKT signaling pathway, the factors that activate this protein kinase B, PI3K/AKT-breast cancer mutations, PI3K/AKT/mTOR-inhibitors, and the relationship between everolimus, temsirolimus and endocrine therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Terapia de Alvo Molecular , Fosfatidilinositol 3-Quinase/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos
14.
Ann Anat ; 219: 89-93, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29621567

RESUMO

Saliva is currently used as a reliable diagnostic fluid in a wide range of local and systemic diseases. However, the link between salivary diagnosis and the inflammatory process in autoimmune diseases has not yet been explored. The aim of our study is to assess possible correlations between salivary inflammatory markers and systemic lupus erythematosus (SLE). Patients fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) diagnosis criteria were included. Salivary and serum levels of interleukin-6 (IL-6), leptin, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) were determined using stochastic sensors. Serum leptin and IL-6 had significantly higher levels in SLE patients compared to non-SLE. Also, salivary IL-6 levels highly correlated with the serum IL-6 levels. A positive correlation was found between salivary and serum levels of IL-6, signaling salivary IL-6 as a reliable marker for assessing the inflammation process in SLE.


Assuntos
Quimiocina CCL2/análise , Interleucina-6/análise , Leptina/análise , Lúpus Eritematoso Sistêmico/diagnóstico , Inibidor 1 de Ativador de Plasminogênio/análise , Saliva/química , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Feminino , Humanos , Inflamação/diagnóstico , Interleucina-6/sangue , Leptina/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/metabolismo , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/metabolismo , Soro/química
15.
Dis Markers ; 2016: 4517492, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27642215

RESUMO

Squamous cells carcinoma (SCC) is the second most frequent of the keratinocyte-derived malignancies after basal cell carcinoma and is associated with a significant psychosocial and economic burden for both the patient himself and society. Reported risk factors for the malignant transformation of keratinocytes and development of SCC include ultraviolet light exposure, followed by chronic scarring and inflammation, exposure to chemical compounds (arsenic, insecticides, and pesticides), and immune-suppression. Despite various available treatment methods and recent advances in noninvasive or minimal invasive diagnostic techniques, the risk recurrence and metastasis are far from being negligible, even in patients with negative histological margins and lymph nodes. Analyzing normal, dysplastic, and malignant keratinocyte proteome holds special promise for novel biomarker discovery in SCC that could be used in the future for early detection, risk assessment, tumor monitoring, and development of targeted therapeutic strategies.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Cutâneas/diagnóstico , Biomarcadores Tumorais/genética , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/patologia , Proteoma/genética , Proteoma/metabolismo , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
16.
Dis Markers ; 2016: 9831237, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27578920

RESUMO

Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC.


Assuntos
Biomarcadores/análise , Carcinoma Basocelular/patologia , Perfilação da Expressão Gênica , Proteoma/análise , Proteômica/métodos , Neoplasias Cutâneas/patologia , Animais , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo
17.
Periodontol 2000 ; 69(1): 68-82, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26252402

RESUMO

Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.


Assuntos
Queratinócitos/fisiologia , Mucosa Bucal/citologia , Transdução de Sinais , Células-Tronco/fisiologia , Proteínas Morfogenéticas Ósseas/metabolismo , Morte Celular , Diferenciação Celular , Proliferação de Células , Epitélio/fisiologia , Humanos , Doenças Periodontais/patologia , Células-Tronco/classificação , Cicatrização
18.
Pneumologia ; 58(2): 89-94, 2009.
Artigo em Romano | MEDLINE | ID: mdl-19637760

RESUMO

Smoking, one of the avoidable causes of mortality, is considered a major risk factor for cardiovascular diseases, chronic obstructive pulmonary diseases, and bronchopulmonary cancer. Many studies suggest that nicotine induces vasoconstriction, not only in coronary arteries but also in peripheral vessels, hypertension, pro-atherogenic effects, due to increase of platelet activation and fatty acids concentration, alterations of endothelial-cell shapes, as well as endothelial-cell proliferation. The main affected vascular biochemical parameters are: endothelin-1, cholesterol, triglycerides, lipoproteins, C-reactive protein, nitric oxide, fibrinogen, and uric acid. Cigarette smoke induces inflammation in respiratory epithelium, through local irritation due to release of oxidants, aldehydes, acids, ammonium; impaired ciliar function, and retention of mucus and toxins, followed by infection; carcinogenesis due to oncogene-expression induced by oxidants, aromatic hydrocarbons, and nitrosamines. These effects are induced by alterations of endothelin-1, nitric oxide, IL1, IL6, TNF, and the CYP Enzyme System. Saliva is the first biological fluid encountered by the cigarette smoke. In vitro and in vivo salivary exposure to cigarette smoke has been shown to determine changes of concentrations of lactate dehydrogenase, amylase, and uric acid, in saliva--important factors of the antioxidant salivary system. Such changes may promote occurrence of upper digestive cancers.


Assuntos
Biomarcadores/metabolismo , Homeostase/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Fumar/efeitos adversos , Fumar/metabolismo , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Colesterol/metabolismo , Endotelina-1/metabolismo , Fibrinogênio/metabolismo , Humanos , Lipoproteínas/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Óxido Nítrico/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Fatores de Risco , Saliva/efeitos dos fármacos , Saliva/metabolismo , Fumar/sangue , Fumar/fisiopatologia , Triglicerídeos/metabolismo , Ácido Úrico/metabolismo
19.
J Med Life ; 2(2): 124-32, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20108531

RESUMO

Saliva, the most available and non-invasive biofluid of the human body, permanently "bathes" the oral cavity and is trying to cope with an ever-changing milieu. The oral cavity, a very complex and unique milieu due to its dual function, is the only place in the body where the mineralized tissue is exposed to the external environment in which there are complex interactions between various surfaces: host soft and hard tissues, food, air, and microorganisms. Saliva includes a large number of inorganic and organic compounds, which act as a "mirror of the body's health." In addition to its other functions, saliva could constitute the first line of defense against oxidative stress. Due to its composition and functions, saliva could have a significant role in controlling and/or modulating oxidative damages in the oral cavity. As a diagnostic fluid, saliva offers distinctive advantages over serum. Furthermore, saliva may provide a cost-effective approach for the screening of large populations. Gland-specific saliva can be used for diagnosis of pathology specific to one of the major salivary glands. Whole saliva, however, is most frequently used for diagnosis of systemic diseases. As we enter the era of genomic medicine, sialochemistry will play an increasingly important role in the early detection, the monitoring and progression of the systemic and oral diseases. We reviewed the current data within literature and of our research concerning clinical potential of the saliva.


Assuntos
Saliva/fisiologia , Fibrose Cística/diagnóstico , Alimentos , Humanos , Infecções/diagnóstico , Íons/análise , Doenças da Boca/diagnóstico , Compostos Orgânicos/análise , Saliva/química , Saliva/enzimologia , Saliva/microbiologia , Doenças das Glândulas Salivares/diagnóstico , Glândulas Salivares/citologia , Glândulas Salivares/patologia
20.
Biofactors ; 33(2): 129-36, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19346588

RESUMO

Saliva is the first biological fluid that inhaled cigarette smoke (CS) encounters. CS contains several carcinogens known to initiate and promote tumourigenesis and metastasis. One of the aims of this study was to establish if glutathione peroxidase and gamma-glutamyltranspherase (GGT) could be used as possible markers for evaluating the oral oxidative stress caused by smoking. The effect of CS on free radical generation was investigated using two methods. Using different assays, different antioxidants present in saliva may be evidenced due to the different principles on which they are based. Our results indicate that exposure to CS caused a statistically significant decrease of both salivary glutathione peroxidase (p < 0.01) and salivary GGT (p < 0.01). We also found that exposure to CS caused a statistically significant decrease of salivary total antioxidant status (p < 0.01). Such decreases may have a consistent role in the mechanisms by which the toxic effects of CS initiate oral inflammatory diseases, promote precancerous transformations, and destroy the oral cavity homeostasis. Therefore the evaluation of total antioxidant capacity of saliva is important but it must be done together with the evaluation of salivary specific markers of oxidative stress, such as uric acid, albumin and possibly, GGT.


Assuntos
Antioxidantes/metabolismo , Glutationa Peroxidase/metabolismo , Saliva/enzimologia , Fumar/metabolismo , gama-Glutamiltransferase/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Estresse Oxidativo , Saliva/química , Saliva/metabolismo , Ácido Úrico/metabolismo
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