Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
1.
Cancer Immunol Immunother ; 73(3): 46, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349444

RESUMO

Immunophenotypic analysis of breast cancer microenvironment is gaining attraction as a clinical tool improving breast cancer patient stratification. The aim of this study is to evaluate proliferating CD8 + including CD8 + TCF1 + Τ cells along with PD-L1 expressing tissue-associated macrophages among different breast cancer subtypes. A well-characterized cohort of 791 treatment-naïve breast cancer patients was included. The analysis demonstrated a distinct expression pattern among breast cancer subtypes characterized by increased CD8 + , CD163 + and CD163 + PD-L1 + cells along with high PD-L1 status and decreased fraction of CD8 + Ki67 + T cells in triple negative (TNBC) and HER2 + compared to luminal tumors. Kaplan-Meier and Cox univariate survival analysis revealed that breast cancer patients with high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + cells, PD-L1 score and CD163 + PD-L1 + cells are likely to have a prolonged relapse free survival, while patients with high CD163 + cells have a worse prognosis. A differential impact of high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + T cells, CD163 + PD-L1 + macrophages and PD-L1 status on prognosis was identified among the various breast cancer subtypes since only TNBC patients experience an improved prognosis compared to patients with luminal A tumors. Conversely, high infiltration by CD163 + cells is associated with worse prognosis only in patients with luminal A but not in TNBC tumors. Multivariate Cox regression analysis in TNBC patients revealed that increased CD8 + [hazard ratio (HR) = 0.542; 95% confidence interval (CI) 0.309-0.950; p = 0.032), CD8 + TCF1 + (HR = 0.280; 95% CI 0.101-0.779; p = 0.015), CD163 + PD-L1 + (HR: 0.312; 95% CI 0.112-0.870; p = 0.026) cells along with PD-L1 status employing two different scoring methods (HR: 0.362; 95% CI 0.162-0.812; p = 0.014 and HR: 0.395; 95% CI 0.176-0.884; p = 0.024) were independently linked with a lower relapse rate. Multivariate analysis in Luminal type A patients revealed that increased CD163 + was independently associated with a higher relapse rate (HR = 2.360; 95% CI 1.077-5.170; p = 0.032). This study demonstrates that the evaluation of the functional status of CD8 + T cells in combination with the analysis of immunosuppressive elements could provide clinically relevant information in different breast cancer subtypes.


Assuntos
Antígeno B7-H1 , Neoplasias de Mama Triplo Negativas , Humanos , Antígeno Ki-67 , Recidiva Local de Neoplasia , Linfócitos T CD8-Positivos , Macrófagos , Doença Crônica , Microambiente Tumoral
2.
Ann Rheum Dis ; 83(3): 342-350, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38050005

RESUMO

OBJECTIVES: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients. METHODS: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed. Synovial tissue specimens from patients with inflammatory arthritis and aorta tissue were used as disease control samples. Senescent cells and their histological origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype by triple costaining. GCA or PMR artery culture supernatants were applied to fibroblasts, HUVECs and monocytes with or without IL-6R blocking agent to explore the induction of IL-6-associated cellular senescence. RESULTS: Senescent cells were present in GCA arteries at higher proportion compared with PMR (9.50% vs 2.66%, respectively, p<0.0001) and were mainly originated from fibroblasts, macrophages and endothelial cells. IL-6 was expressed by senescent fibroblasts, and macrophages while MMP-9 by senescent fibroblasts only. IL-6(+) senescent cells were associated with the extension of vascular inflammation (transmural inflammation vs adventitia limited disease: 10.02% vs 4.37%, respectively, p<0.0001). GCA but not PMR artery culture supernatant could induce IL-6-associated senescence that was partially inhibited by IL-6R blockade. CONCLUSIONS: Senescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk, suggesting a potential implication in disease pathogenesis.


Assuntos
Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Arterite de Células Gigantes/complicações , Interleucina-6/genética , Metaloproteinase 9 da Matriz/genética , Células Endoteliais/metabolismo , Estudos Retrospectivos , Polimialgia Reumática/complicações , Fenótipo , Senescência Celular , Inflamação/complicações
3.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38279253

RESUMO

In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.


Assuntos
Inteligência Artificial , Neoplasias , Humanos , Animais , Camundongos , Neoplasias/diagnóstico , Inflamação , Biomarcadores , Hiperplasia , Sistema Digestório
4.
Klin Monbl Augenheilkd ; 241(1): 84-87, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36781159

RESUMO

This is a unique case of retinoschisis as an ocular manifestation of brucellosis. A 38-year-old male presented with recurrent episodes of bilateral eye redness, predominately in his left eye. His visual acuity was not affected, and he did not report any other symptoms. On slit lamp examination, binocular Koeppe nodules of the iris and cells in the left anterior chamber were observed. Fundoscopy followed by meticulous multimodal imaging confirmed left inferior retinoschisis. The patient was diagnosed with panuveitis, and a series of laboratory examinations revealed positive anti-IgM Brucella antibodies. Ocular brucellosis can cause variable, atypical, and serious presentations, hence, early diagnosis is paramount to avoid complications.


Assuntos
Brucella , Brucelose , Pan-Uveíte , Retinosquise , Uveíte , Humanos , Masculino , Adulto , Uveíte/diagnóstico , Uveíte/complicações , Brucelose/complicações , Brucelose/diagnóstico , Brucelose/tratamento farmacológico
5.
Eur Respir J ; 60(2)2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35086840

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the respiratory system can progress to a multisystemic disease with aberrant inflammatory response. Cellular senescence promotes chronic inflammation, named senescence-associated secretory phenotype (SASP). We investigated whether coronavirus disease 2019 (COVID-19) is associated with cellular senescence and SASP. METHODS: Autopsy lung tissue samples from 11 COVID-19 patients and 43 age-matched non-COVID-19 controls with similar comorbidities were analysed by immunohistochemistry for SARS-CoV-2, markers of senescence and key SASP cytokines. Virally induced senescence was functionally recapitulated in vitro, by infecting epithelial Vero-E6 cells and a three-dimensional alveosphere system of alveolar type 2 (AT2) cells with SARS-CoV-2 strains isolated from COVID-19 patients. RESULTS: SARS-CoV-2 was detected by immunocytochemistry and electron microscopy predominantly in AT2 cells. Infected AT2 cells expressed angiotensin-converting enzyme 2 and exhibited increased senescence (p16INK4A and SenTraGor positivity) and interleukin (IL)-1ß and IL-6 expression. In vitro, infection of Vero-E6 cells with SARS-CoV-2 induced senescence (SenTraGor), DNA damage (γ-H2AX) and increased cytokine (IL-1ß, IL-6, CXCL8) and apolipoprotein B mRNA-editing (APOBEC) enzyme expression. Next-generation sequencing analysis of progenies obtained from infected/senescent Vero-E6 cells demonstrated APOBEC-mediated SARS-CoV-2 mutations. Dissemination of the SARS-CoV-2-infection and senescence was confirmed in extrapulmonary sites (kidney and liver) of a COVID-19 patient. CONCLUSIONS: We demonstrate that in severe COVID-19, AT2 cells infected by SARS-CoV-2 exhibit senescence and a proinflammatory phenotype. In vitro, SARS-CoV-2 infection induces senescence and inflammation. Importantly, infected senescent cells may act as a source of SARS-CoV-2 mutagenesis mediated by APOBEC enzymes. Therefore, SARS-CoV-2-induced senescence may be an important molecular mechanism of severe COVID-19, disease persistence and mutagenesis.


Assuntos
COVID-19 , SARS-CoV-2 , Senescência Celular , Citocinas/metabolismo , Humanos , Inflamação , Interleucina-6 , Pulmão/metabolismo , Mutagênese , Fenótipo
6.
Acta Derm Venereol ; 94(2): 168-72, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23995395

RESUMO

Herpes zoster neural injury was assessed by determining cutaneous nerve density in skin biopsies from the affected dermatomes of 35 adult patients with herpes zoster in the acute phase and 3 months post-treatment, using protein gene product 9.5 immunohistochemistry. In contrast to the significant increase in subepidermal nerve fibre density (11.77 ± 4.88/mm vs. 13.29 ± 5.74/mm, p = 0.045) after 3 months, no differences were found in epidermal free nerve endings (2.43 ± 2.35/mm and 2.8 ± 2.86/mm, p = 0.168). Patients with post-herpetic neuralgia had significantly lower subepidermal nerve fibre densities (9.7 ± 2.05/mm vs. 14.72 ± 6.13/mm, p = 0.011) compared with non-post-herpetic neuralgia patients. No differences in cutaneous nerve density were found in relation to antiviral therapy. In conclusion, 3 months after acute infection, no sign of epidermal innervation recovery is observed, while the increased subepidermal nerve fibre density in the affected dermatomes probably reflects nerve regeneration that is not affected by antiviral agent type. Subepidermal nerve fibre density is decreased in patients with post-herpetic neuralgia 3-months post-acute herpes zoster infection.


Assuntos
Herpes Zoster/patologia , Fibras Nervosas/patologia , Neuralgia Pós-Herpética/patologia , Pele/inervação , Pele/patologia , 2-Aminopurina/análogos & derivados , 2-Aminopurina/uso terapêutico , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Biomarcadores/metabolismo , Biópsia , Bromodesoxiuridina/análogos & derivados , Bromodesoxiuridina/uso terapêutico , Famciclovir , Feminino , Herpes Zoster/tratamento farmacológico , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pele/metabolismo , Ubiquitina Tiolesterase/metabolismo , Valaciclovir , Valina/análogos & derivados , Valina/uso terapêutico
7.
J Fungi (Basel) ; 9(6)2023 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-37367619

RESUMO

Rheumatoid arthritis (RA) patients deal with a higher risk of bacterial and fungal infections compared to the general population because of their dysregulated immune system as well as the immunosuppressive therapy they usually receive. Scedosporium spp. is a fungal pathogen responsible for cutaneous, lung, central nervous system, and eye infections, mostly in immunocompromised patients, leading to death in disseminated cases. We report the case of an 81-year-old woman with rheumatoid arthritis treated with steroids and an IL-6 inhibitor who was diagnosed with scedosporiosis of the upper limb. She was treated with voriconazole for one month, which was discontinued due to adverse events, and when scedosporiosis relapsed, she switched to itraconazole. We also reviewed the current literature on RA patients presenting with Scedosporium infections. Early and accurate diagnosis of scedosporiosis has therapeutic and prognostic implications, as traditionally this fungus is resistant to commonly used antifungals. Clinical alertness regarding uncommon infections, including fungal, in patients with autoimmune diseases on immunomodulatory agents is essential for effective treatment.

8.
Antibiotics (Basel) ; 12(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37887250

RESUMO

Nosocomial outbreaks of multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) are often reported worldwide, mostly associated with a small number of multilocus-sequence types of E. hormaechei and E. cloacae strains. In Europe, the largest clonal outbreak of blaNDM-1-producing ECC has been recently reported, involving an ST182 E. hormaechei strain in a Greek teaching hospital. In the current study, we aimed to further investigate the genetic make-up of two representative outbreak isolates. Comparative genomics of whole genome sequences (WGS) was performed, including whole genome-based taxonomic analysis and in silico prediction of virulence determinants of the bacterial cell surface, plasmids, antibiotic resistance genes and virulence factors present on genomic islands. The enterobacterial common antigen and the colanic antigen of the cell surface were identified in both isolates, being similar to the gene clusters of the E. hormaechei ATCC 49162 and E. cloacae ATCC 13047 type strains, whereas the two strains possessed different gene clusters encoding lipopolysaccharide O-antigens. Other virulence factors of the bacterial cell surface, such as flagella, fimbriae and pili, were also predicted to be encoded by gene clusters similar to those found in Enterobacter spp. and other Enterobacterales. Secretion systems and toxin-antitoxin systems, which also contribute to pathogenicity, were identified. Both isolates harboured resistance genes to multiple antimicrobial classes, including ß-lactams, aminoglycosides, quinolones, chloramphenicol, trimethoprim, sulfonamides and fosfomycin; they carried blaTEM-1, blaOXA-1, blaNDM-1, and one of them also carried blaCTXM-14, blaCTXM-15 and blaLAP-2 plasmidic alleles. Our comprehensive analysis of the WGS assemblies revealed that blaNDM-1-producing outbreak isolates possess components of the bacterial cell surface as well as genomic islands, harbouring resistance genes to several antimicrobial classes and various virulence factors. Differences in the plasmids carrying ß-lactamase genes between the two strains have also shown diverse modes of acquisition and an ongoing evolution of these mobile elements.

9.
Cureus ; 15(3): e36594, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37095804

RESUMO

Ectopic or accessory breast tissue may occur in primitive embryonic milk lines or locations other than the milk line. The same pathology arising in breast tissue may occur less frequently in ectopic breast tissue. Fibroadenomas rarely occur in ectopic breast tissue, with less than 50 reported cases in the English literature, despite being the most common benign breast neoplasms. Diagnosing fibroadenoma in ectopic breast tissue can be challenging due to the lack of clinical suspicion and the atypical findings in imaging studies. Treatment consists of surgical excision. In this manuscript, we present a case of a 24-year-old patient with a fibroadenoma of the left axilla arising in bilateral axillary ectopic breast tissue, and we comprehensively review the literature.

10.
Microorganisms ; 11(7)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37512983

RESUMO

The coronavirus disease (COVID-19) pandemic increased the incidence of severe infections caused by multidrug-resistant (MDR) pathogens among critically ill patients, such as Acinetobacter baumannii (AB), whose bloodstream infections (BSIs) have been associated with significant mortality. Whether there is any difference in outcome between COVID-19 and non-COVID-19 patients with AB BSI still remains unknown. We conducted a retrospective study comparing clinical characteristics and outcomes of COVID-19 versus non-COVID-19 critically ill patients with AB BSI. Overall, 133 patients with AB BSI (102 COVID-19, 31 non-COVID-19) were studied. The 28-day mortality rate was high and did not differ significantly (69.6% COVID-19 vs. 61.3% non-COVID-19, p = 0.275). Patients with septic shock had a higher mortality rate irrespective of their status with the majority of deaths occurring during the first 7 days. COVID-19 patients were more likely to have ventilator-associated pneumonia (VAP) as the source of BSI (55.8% vs. 22.3%, respectively, p = 0.0001) and were more likely to develop acute respiratory distress syndrome (ARDS) (78.4% vs. 48.4%, respectively, p = 0.001), sepsis (86.3% vs. 67.7%, respectively, p = 0.03), and septic shock (88.3% vs. 58.1%, respectively, p = 0.007) compared to the non-COVID-19 patient group. In conclusion, COVID-19 patients with A. baumannii BSI have a high rate of mortality and more often develop septic shock, while VAP is the main origin of their BSI.

11.
Anticancer Res ; 43(4): 1709-1717, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36974793

RESUMO

BACKGROUND/AIM: Adenoid cystic carcinoma (ACC) is an aggressive neoplasm even though it has low-grade histological appearance and slow growth. The aim of this study was to identify the immunohistochemical and molecular characteristics of ACC, as well as their correlation with the clinical course of patients. PATIENTS AND METHODS: This is a retrospective multicenter analysis. We included 50 patients diagnosed with ACC in the head and neck between 2000 and 2021. The expression of MYB proto-oncogene transcription factor (MYB), neurotrophic tyrosine kinase receptor (NTRK), human epidermal receptor-2 (HER-2), and Ki-67 was examined through immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). We also performed a clinical follow-up of the patients. RESULTS: The median age of the patients was 58.5 years; moreover, 54% of the patients were male. Compared with female patients, male patients were at a higher risk of both recurrence and death. No HER-2-positive cases were revealed. MYB expression was positive in 28 (56%) cases. However, MYB expression did not significantly affect survival. NTRK expression was positive in eight (16%) cases. NTRK-positive patients had worse overall survival (OS) than NTRK-negative patients (p=0.0246). Additionally, the percentage of NTRK-stained cells was negatively correlated with disease-free survival (p=0.0016) and OS (p=0.0027). CONCLUSION: There was no correlation between MYB positivity and survival. Contrarily, NTRK-positive patients had worse survival, indicating that NTRK is a negative prognostic factor. Tropomyosin receptor kinase inhibitors can be used to treat these patients. Furthermore, MYB-targeted inhibitors are promising therapeutic agents.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Adenoide Cístico/patologia , Receptores Proteína Tirosina Quinases , Hibridização in Situ Fluorescente , Neoplasias de Cabeça e Pescoço/genética , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo
12.
Nature ; 444(7119): 633-7, 2006 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-17136093

RESUMO

Recent studies have indicated the existence of tumorigenesis barriers that slow or inhibit the progression of preneoplastic lesions to neoplasia. One such barrier involves DNA replication stress, which leads to activation of the DNA damage checkpoint and thereby to apoptosis or cell cycle arrest, whereas a second barrier is mediated by oncogene-induced senescence. The relationship between these two barriers, if any, has not been elucidated. Here we show that oncogene-induced senescence is associated with signs of DNA replication stress, including prematurely terminated DNA replication forks and DNA double-strand breaks. Inhibiting the DNA double-strand break response kinase ataxia telangiectasia mutated (ATM) suppressed the induction of senescence and in a mouse model led to increased tumour size and invasiveness. Analysis of human precancerous lesions further indicated that DNA damage and senescence markers cosegregate closely. Thus, senescence in human preneoplastic lesions is a manifestation of oncogene-induced DNA replication stress and, together with apoptosis, provides a barrier to malignant progression.


Assuntos
Transformação Celular Neoplásica/genética , Senescência Celular/genética , Dano ao DNA , Oncogenes , Animais , Proteínas de Ciclo Celular/genética , Linhagem Celular , Ciclina E/genética , Inibidor p16 de Quinase Dependente de Ciclina/fisiologia , DNA , Replicação do DNA , Genes mos , Humanos , Camundongos , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia
13.
Ultrastruct Pathol ; 36(6): 387-99, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23181508

RESUMO

Integrins mediate cell adhesion to the extracellular matrix. Integrin alphavbeta3 recognizes the RGD motif as a ligand-binding site and has been associated with high malignant potential in breast cancer cells, signaling the onset of widespread metastasis. In recent years, several antagonists of integrin alphavbeta3, including RGD peptides, have been used as potential anti-cancer agents. In the present work, the effect of the linear RGD hexapeptide GRGDSP was studied, for the first time, on breast tumor explants, as well as on well-spread human breast cancer cells from primary cultures, using the explant technique, to clarify the role of this peptide in the suppression of breast cancer cell migration. The results showed that incubation of breast tumor explants with RGD peptide at the beginning of culture development inhibited completely the migration of cancer cells out of the tissue fragment as revealed by electron microscopy. RGD incubation of well-spread breast cancer cells from primary culture resulted in rounding and shrinkage of the cells accompanied by altered distribution of integrin alphavbeta3 and concomitant F-actin cytoskeletal disorganization, as revealed by immunofluorescence. Electron immunocytochemistry showed aggregation of integrin alphavbeta3 at the cell periphery and its detection in noncoated vesicles. However, Western immunoblotting showed no change in beta3 subunit expression, despite the altered distribution of the integrin alphavbeta3. In light of the above, it appears that the RGD peptide plays an important role in the modulation of cell motility and in the perturbation of cell attachment affecting the malignant potential of breast cancer cells in primary cultures.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Integrina alfaVbeta3/antagonistas & inibidores , Oligopeptídeos/farmacologia , Actinas/metabolismo , Antineoplásicos/metabolismo , Western Blotting , Neoplasias da Mama/ultraestrutura , Carcinoma Ductal de Mama/ultraestrutura , Forma Celular/efeitos dos fármacos , Feminino , Humanos , Integrina alfaVbeta3/metabolismo , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Microscopia Imunoeletrônica , Oligopeptídeos/metabolismo , Cultura Primária de Células , Ligação Proteica , Técnicas de Cultura de Tecidos , Células Tumorais Cultivadas
14.
Nature ; 434(7035): 907-13, 2005 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-15829965

RESUMO

DNA damage checkpoint genes, such as p53, are frequently mutated in human cancer, but the selective pressure for their inactivation remains elusive. We analysed a panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis. Progression to carcinoma was associated with p53 or 53BP1 inactivation and decreased apoptosis. A DNA damage response was also observed in dysplastic nevi and in human skin xenografts, in which hyperplasia was induced by overexpression of growth factors. Both lung and experimentally-induced skin hyperplasias showed allelic imbalance at loci that are prone to DNA double-strand break formation when DNA replication is compromised (common fragile sites). We propose that, from its earliest stages, cancer development is associated with DNA replication stress, which leads to DNA double-strand breaks, genomic instability and selective pressure for p53 mutations.


Assuntos
Dano ao DNA , Instabilidade Genômica/genética , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle , Desequilíbrio Alélico/genética , Apoptose , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Quinase do Ponto de Checagem 2 , Fragilidade Cromossômica , Dano ao DNA/genética , Replicação do DNA , Progressão da Doença , Ativação Enzimática , Genes p53/genética , Histonas/metabolismo , Humanos , Hiperplasia/enzimologia , Hiperplasia/genética , Hiperplasia/metabolismo , Hiperplasia/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutação/genética , Fosfoproteínas/metabolismo , Fosforilação , Lesões Pré-Cancerosas/enzimologia , Lesões Pré-Cancerosas/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53
15.
J Thromb Thrombolysis ; 31(2): 154-64, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20953817

RESUMO

We sought to evaluate the association between C-reactive protein (CRP) sampled on admission and short- and long-term mortality in patients with acute coronary syndromes (ACS) undergoing early invasive treatment. Baseline levels of CRP were determined in 2,974 patients with moderate and high-risk ACS undergoing an early invasive treatment strategy in the large-scale randomized ACUITY trial. The relationship of CRP to 30-day and 1-year clinical outcomes were assessed according to quartiles of CRP values. Patients with CRP levels in the fourth quartile compared to the first quartile had significantly higher 30-day mortality (2.3 vs. 0.3%, P = 0.0004) and 1-year mortality (5.5 vs. 2.8%, P = 0.0003). CRP level as a continuous variable was associated with 30-day mortality (OR [95% CI] for one unit increase in logarithmically transformed CRP level = 1.42 [1.08-1.89], P = 0.01) and 1-year mortality (OR [95% CI] = 1.24, [1.04-1.47], P = 0.02). By multivariable analysis, higher baseline CRP levels independently predicted 30-day and 1-year mortality, a relationship that was particularly strong for patients with the highest quartile of CRP (OR [95% CI] = 5.19 [1.14-23.68], P = 0.009). In troponin-positive patients, increasing quartiles of CRP were associated with a trend for 30-day mortality (P (trend) = 0.08) and a significant increase in 1-year mortality (P (trend) = 0.02); this relationship was not present in troponin-negative patients. Baseline CRP level is a powerful independent predictor of both early and late mortality in patients with ACS being treated with an early invasive strategy, especially in troponin positive patients.


Assuntos
Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Proteína C-Reativa/análise , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Tempo
16.
Cureus ; 13(3): e13773, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33842149

RESUMO

Paragangliomas are rare lesions of the endocrine system that can be treated either by embolization preoperatively followed by surgical excision or by surgical excision or radiotherapy. In this report, we present an extremely rare location of a nonfunctional paraganglioma in the head and neck region, located in the right supraclavicular fossa, which was misdiagnosed as a thyroid tumor, in a 72-year-old female patient. Imaging revealed a 2.5 × 4.5 × 2 cm well-defined vascularized mass. Fine-needle aspiration (FNA) on the tumor was not diagnostic initially; however, a third attempt revealed thyroid cells suggesting the existence of an ectopic thyroid tumor. FNA was additionally performed on the right thyroid lobe, revealing atypical follicular colloid cells of the Bethesda 3 category. Therefore, the excision of the ectopic thyroid tumor along with right lobectomy was planned. No embolization was initiated preoperatively in this case. Histopathology revealed that the supraclavicular mass was a paraganglioma. Paragangliomas supplied by the subclavian, innominate, and common carotid artery are rarely reported, and to our knowledge, this is the third case to be reported worldwide.

17.
Viruses ; 13(6)2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198719

RESUMO

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using 'in-house' methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of 'non-responders' a misnomer.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Antígenos Virais/imunologia , Teste Sorológico para COVID-19/normas , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Anticorpos Antivirais/metabolismo , Antígenos Virais/metabolismo , Sítios de Ligação de Anticorpos , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste Sorológico para COVID-19/estatística & dados numéricos , Humanos , Imunidade Humoral/imunologia , Imunoglobulina G/sangue , Masculino , Sensibilidade e Especificidade , Soroconversão , Adulto Jovem
18.
Am J Pathol ; 175(1): 376-91, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19541929

RESUMO

Osteosarcoma is the most common primary bone cancer. Mutations of the RB gene represent the most frequent molecular defect in this malignancy. A major consequence of this alteration is that the activity of the key cell cycle regulator E2F1 is unleashed from the inhibitory effects of pRb. Studies in animal models and in human cancers have shown that deregulated E2F1 overexpression possesses either "oncogenic" or "oncosuppressor" properties, depending on the cellular context. To address this issue in osteosarcomas, we examined the status of E2F1 relative to cell proliferation and apoptosis in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53. Collectively, our data demonstrated that high E2F1 levels exerted a growth-suppressing effect that relied on the integrity of the DNA damage response network. Surprisingly, induction of p73, an established E2F1 target, was also DNA damage response-dependent. Furthermore, a global proteome analysis associated with bioinformatics revealed novel E2F1-regulated genes and potential E2F1-driven signaling networks that could provide useful targets in challenging this aggressive neoplasm by innovative therapies.


Assuntos
Neoplasias Ósseas/metabolismo , Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica , Osteossarcoma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/fisiologia , Western Blotting , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Proliferação de Células , Criança , Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA/metabolismo , Fator de Transcrição E2F1/genética , Eletroforese em Gel Bidimensional , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Osteossarcoma/genética , Proteína Tumoral p73 , Proteína Supressora de Tumor p53/deficiência , Proteínas Supressoras de Tumor/metabolismo , Adulto Jovem
19.
J Oral Pathol Med ; 39(9): 667-71, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20618607

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. METHODS: Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. RESULTS: Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. CONCLUSION: Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/imunologia , Distribuição de Qui-Quadrado , Feminino , Seguimentos , Humanos , Inflamação/patologia , Linfócitos do Interstício Tumoral , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Células Estromais/patologia , Neoplasias da Língua/imunologia
20.
Pathogens ; 9(10)2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33080905

RESUMO

Onychomycosis is considered as one of the major public health problems with a global distribution associated with geographic, demographic and environmental factors, underlying comorbidities and immunodeficiency disorders. This study was conducted to investigate the etiological agents of onychomycosis, in Northwestern Greece during a 7-year period. The study population included 1095 outpatients with clinically suspected onychomycosis that presented to the University Hospital of Ioannina, NW Greece (2011-2017). Samples were examined for causative fungi, and mycological identification was established using standard mycological methods. Demographic data of each patient, comorbidities, localization of infection and history of previous fungal infection were collected. Onychomycosis was diagnosed in 317 of the 1095 suspected cases (28.9%) and the most frequently isolated pathogens were yeasts (50.8%) followed by dermatophytes (36.9%) and non-dermatophyte molds (NDMs) (12.3%). Dermatophytes were mostly involved in toenail onychomycosis (90.6%) and more commonly affected males than females (57.3% vs. 42.7%), while the predominantly isolated pathogen was Τrichophyton rubrum (74.4%) followed by Τrichophyton interdigitale (21.4%). Candida albicans was the most prevalent isolated yeast (82%), whereas among the cases with onychomycosis due to NDMs, Aspergillus spp. were isolated as the principal species (59%). Continuous monitoring should be performed in order to identify possible trends and shifts in species isolation rates and to evaluate the impact of onychomycosis among the general population and high-risk groups.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA