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1.
Front Oral Health ; 5: 1378566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567313

RESUMO

Introduction: The human host defense peptide LL-37 is a component of the innate immune defense mechanisms of the oral cavity against colonization by microbes associated with periodontal disease. We have previously shown that the active form of vitamin D, 1,25(OH)2D3, can induce the expression of LL-37 in gingival epithelial cells (GEC), and prevent the invasion and growth of periopathogenic bacteria in these cells. Further, experimental vitamin D deficiency resulted in increased gingival inflammation and alveolar bone loss. Epidemiological studies have shown associations between vitamin D deficiency and periodontal disease in humans, suggesting application of vitamin D could be a useful therapeutic approach. Further, since we have shown the local activation of vitamin D by enzymes expressed in the GEC, we hypothesized that we could observe this enhancement with the stable, and inexpensive inactive form of vitamin D, which could be further increased with epigenetic regulators. Methods: We treated 3-dimensional primary cultures of GEC topically with the inactive form of vitamin D, in the presence and absence of selected histone deacetylase (HDAC) inhibitors. LL-37 mRNA levels were quantified by quantitative RT-PCR, and inhibition of invasion of bacteria was measured by fluorescence microscopy. Results: Vitamin D treatment led to an induction of LL-37 mRNA levels, as well as an inhibition of pro-inflammatory cytokine secretion. This effect was further enhanced by HDAC inhibitors, most strongly when the HDAC inhibitor, phenyl butyrate (PBA) was combined with Vitamin D3. This was observed both in solution and in a prototype gel formulation using sodium butyrate. Finally, this combination treatment led to an increase in the antimicrobial activity against infection by Porphyromonas gingivalis and Filifactor alocis, bacteria associated with periodontal lesions, as well as herpes simplex virus, which has also been shown to be associated with periodontal lesions. Conclusions: Our results demonstrate that a combination of inactive vitamin D and sodium butyrate could be developed as a safe treatment for periodontal disease.

2.
Saudi J Kidney Dis Transpl ; 34(4): 305-312, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345585

RESUMO

Endothelial dysfunction in patients with diabetic nephropathy is caused by nontraditional factors in addition to common risk factors (e.g., hypertension) in people with normal kidney function. These nontraditional factors include factors involved in mineral bone disease in these patients. One of these factors is fibroblast growth factor 23 (FGF-23). We aimed to evaluate the relationship between flow-mediated dilatation (FMD) as a measure of endothelial dysfunction and FGF-23. This was a cross-sectional observational study that was conducted on 100 diabetic patients (Group I: 50 patients with nephropathy; Group II: 50 patients without nephropathy) and 50 healthy volunteers (Group III). Serum levels of intact FGF-23, interleukin-6, intact parathyroid hormone, and 25-hydroxyvitamin D (25-(OH)Vit D); estimated insulin resistance; and FMD were evaluated. FGF-23 was significantly higher in Group I (median: 101 pg/mL) and Group II (median: 101 pg/mL) than in Group III (median: 4 pg/mL) (P <0.001), but FGF-23 was not significantly different between Groups I and II. A significant positive correlation was found between serum levels of FGF-23 and phosphorus in Group I. A significant negative correlation was found between serum levels of FGF-23 and 25-(OH)Vit D in Group II. However, FGF-23 failed to show a significant correlation with FMD in patients with diabetic nephropathy. Our data suggest another factor that rises earlier than FGF-23 in diabetic nephropathy and causes endothelial dysfunction.


Assuntos
Nefropatias Diabéticas , Doenças Vasculares , Humanos , Estudos Transversais , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Egito , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos
3.
Saudi J Kidney Dis Transpl ; 33(Supplement): S105-S110, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37675740

RESUMO

Multiple myeloma (MM) is a disease of the elderly. Renal failure is a common complication in MM. In this study, we evaluated clinical and laboratory parameters that might contribute to the recovery of renal function in geriatric MM patients. Twenty-five geriatric patients aged >65 years were retrospectively compared with 20 patients aged <65 years with a diagnosis of MM and renal failure between October 2016 and October 2019. Variables that might be associated with the discontinuation of dialysis in these patients were examined in the 6 months of follow-up after the diagnosis. Among the geriatric patients aged >65 years, 100% remained on regular hemodialysis (HD) at the end of the follow-up period in contrast to eight patients (40%) in the younger group, and this was statistically significant P = 0.001. We have noticed that geriatric patients who required maintenance HD had lower mean hemoglobin concentrations (P = 0.02), and higher mean serum calcium (P = 0.03). Other factors were statistically insignificant. Our study showed that age of >65 years, hemoglobin levels, and serum calcium were significantly different between the group who recovered from renal failure and those who required a continuation of HD, but none was an independent prognostic factor for predicting the probability of recovery from severe renal failure and discontinuation of HD in both groups studied.


Assuntos
Mieloma Múltiplo , Insuficiência Renal , Idoso , Humanos , Cálcio , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Rim/fisiologia , Hemoglobinas
4.
Iran J Kidney Dis ; 15(5): 385-390, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34582373

RESUMO

INTRODUCTION: This study hypothesized that the insulin Degludec may have benefit if used in management of diabetes mellitus after renal transplantation to achieve better control at the critical time of adjustment of immunosuppressive regimens during the first year post transplant. METHODS: Fifty patients with Type 2 diabetes Mellitus after renal transplantation with stable serum creatinine with glycosylated hemoglobin (HbA1C) 7 to 11% were included in the study to receive either Insulin Degludec or Insulin Glargine. Fasting blood glucose, 2 hour post-prandial levels and (HbA1c), were measured at 12, 16, 26, 40, and 52 weeks after renal transplantation also hypoglycemic episodes were documented all through the study. RESULTS: Despite both groups are matched as regards demographic and metabolic data, FPG, and 2h PPG were lower in insulin Degludec group all through the study. HbA1c most pronounced decline, occurred at 52th week of treatment in both groups. The most important clinically relevant finding in our study was that; the overall confirmed hypoglycemia rates and the rate of nocturnal confirmed hypoglycemia was significantly lower with Degludec treated group (P < .001). CONCLUSION: Insulin Degludec provides optimum glycemic control in in the first year post-renal transplant patients with significantly lower rate of hypoglycemia. DOI: 10.52547/ijkd.6131.


Assuntos
Diabetes Mellitus Tipo 2 , Transplante de Rim , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada , Transplante de Rim/efeitos adversos , Projetos Piloto
5.
Rom J Intern Med ; 59(2): 127-133, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33565308

RESUMO

Background. Few data with adequate evidence exists as regards the effect of Cyclosporine (CsA) and mycophenolate mofetil (MMF) on pathological prognostic parameters in patients with steroid resistant focal segmental glomerulosclerosis (FSGS). The purpose of the present study is to compare the effect of cyclosporin and mycophenolate mofetil in addition to steroids on functional and histopathologic renal parameters in patients with steroid resistant FSGS one year after treatment.Material and methods. Thirty-seven adults with primary FSGS patients resistant to steroid therapy consecutively randomized to treatment with either MMF or cyclosporine. Low dose prednisolone added to both groups. Glomerular filtration rate (GFR) and blood pressure (BP) were determined at all examinations and a second renal biopsy was taken 12 months after treatment with either of cyclosporin and mycophenolate mofetil.Results. GFR significantly increased in MMF group p < 0.01 after 6 months and unchanged after 12 months. On the other hand, GFR significantly decrease in CsA group p < 0.001 after 6 months and reduced more after 12 months p < 0.001 compared to base line levels. There was a significant difference of GFR between the 2 groups at 6 months p < 0.001. The extent of proteinuria decreased significantly in CsA group after 12 months p < 0.001. The extent of arteriolar hyalinosis increased significantly in CsA group (0.78 to 1.81 score, p < 0.001) but was unchanged in MMF group (0.93 to 0.96 score), whereas interstitial fibrosis increased to same level in both groups (grade 3).Conclusion. Conversion to MMF in those patients may be superior to CsA as regards GFR after 12 months after treatment in spite of the presence of greater level of protein excretion. The increased arteriolar hyalinosis during CsA treatment most likely results in higher BP compared to MMF treatment in patients with FSGS resistant to steroids.


Assuntos
Ciclosporina/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/fisiopatologia , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adulto , Arteríolas/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Diarreia/fisiopatologia , Resistência a Medicamentos , Quimioterapia Combinada , Oftalmopatias Hereditárias/fisiopatologia , Feminino , Fibrose/patologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/patologia , Glucocorticoides/uso terapêutico , Humanos , Hialina/metabolismo , Enteropatias/fisiopatologia , Masculino , Prednisolona/uso terapêutico , Estudos Prospectivos , Proteinúria , Anormalidades da Pele/fisiopatologia , Resultado do Tratamento , Doenças Vasculares/fisiopatologia
6.
Rom J Intern Med ; 58(2): 75-80, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31955149

RESUMO

BACKGROUND: Early intervention for septic shock is crucial to reduce mortality and improve outcome. There is still a great debate over the exact time of therapeutic plasma exchange (TPE) administration in septic shock patients. This study aims to investigate the effect of early initiation (within 4 hours) of TPE in severe septic shock on hemodynamics & outcome. METHODS: We conducted a prospective, before-after case series study on 16 septic shock patients requiring high doses of vasopressors admitted in two ICUs from Cairo, Egypt. All of our patients received TPE within 4 hours of ICU admission. The fresh frozen plasma exchange volume = 1.5 × plasma volume. RESULTS: In the 16 patients included in the study, mean arterial pressure was significantly improved after the initial TPE (p < 0.002) and norepinephrine dose which significantly reduced post TPE (p < 0.001). In addition, norepinephrine dose to mean arterial pressure significantly improved (p < 0.001). There was reduction of a net 6 hours fluid balances following the first TPE were observed in all the patients (p < 0.03) by a mean of 757 ml. Systemic vascular resistance index was markedly improved post-TPE along with statistically improved cardiac index (p < 0.01). Stroke volume variance was also significantly decreased after the TPE sessions (p < 0.01). C-reactive protein significantly improved after TPE (P < 0.01). CONCLUSION: Early initiation of TPE in severe septic shock patients might improve hemodynamic measures.


Assuntos
Pressão Arterial , Norepinefrina/administração & dosagem , Troca Plasmática/métodos , Choque Séptico/terapia , Volume Sistólico , Resistência Vascular , Vasoconstritores/administração & dosagem , APACHE , Proteína C-Reativa/metabolismo , Intervenção Médica Precoce , Feminino , Mortalidade Hospitalar , Humanos , Ácido Láctico/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Choque Séptico/fisiopatologia , Resultado do Tratamento
7.
Front Psychiatry ; 11: 603875, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488426

RESUMO

Background: COVID-19 prevention and mitigation efforts were abrupt and challenging for most countries with the protracted lockdown straining socioeconomic activities. Marginalized groups and individuals are particularly vulnerable to adverse effects of the pandemic such as human rights abuses and violations which can lead to psychological distress. In this review, we focus on mental distress and disturbances that have emanated due to human rights restrictions and violations amidst the pandemic. We underscore how mental health is both directly impacted by the force of pandemic and by prevention and mitigation structures put in place to combat the disease. Methods: We conducted a review of relevant studies examining human rights violations in COVID-19 response, with a focus on vulnerable populations, and its association with mental health and psychological well-being. We searched PubMed and Embase databases for studies between December 2019 to July 2020. Three reviewers evaluated the eligibility criteria and extracted data. Results: Twenty-four studies were included in the systematic inquiry reporting on distress due to human rights violations. Unanimously, the studies found vulnerable populations to be at a high risk for mental distress. Limited mobility rights disproportionately harmed psychiatric patients, low-income individuals, and minorities who were at higher risk for self-harm and worsening mental health. Healthcare workers suffered negative mental health consequences due to stigma and lack of personal protective equipment and stigma. Other vulnerable groups such as the elderly, children, and refugees also experienced negative consequences. Conclusions: This review emphasizes the need to uphold human rights and address long term mental health needs of populations that have suffered disproportionately during the pandemic. Countries can embed a proactive psychosocial response to medical management as well as in existing prevention strategies. International human rights guidelines are useful in this direction but an emphasis should be placed on strengthening rights informed psychosocial response with specific strategies to enhance mental health in the long-term. We underscore that various fundamental human rights are interdependent and therefore undermining one leads to a poor impact on the others. We strongly recommend global efforts toward focusing both on minimizing fatalities, protecting human rights, and promoting long term mental well-being.

8.
Saudi J Kidney Dis Transpl ; 29(6): 1311-1319, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588961

RESUMO

Enterobacteriaceae are now the predominant pathogens isolated in patients with liver cell failure associated with bloodstream infections. We conducted a retrospective cohort study of patients who were admitted for the diagnosis of hepatorenal failure (HRF) between June 1999 and May 2008 to investigate the risk factors of Enterobacteriaceae bacteremia (EB). EB was defined as the isolation of an EB species from at least one blood culture within three months following diagnosis of HRF. Variables were collected from the medical records and analyzed in relation to EB. Twenty-four (32.5%) of the 73 patients developed EB. The origin of EB was abdominal in 21% of the patients, urinary in 12.5%, pulmonary in 16.5%, and primary in the remaining patients (50%). Two-thirds of EB occurred within 10 days following the development of HRF. The main pathogens were Escherichia coli (44%), Enterobacter species (20%) and Klebsiella pneumoniae (22%). Eighteen patients (75%) with EB died. Variables significantly associated with EB after multivariate analysis were a model for end-stage liver disease score >20 [odds ratio (OR): 2.84, P <0.02], posthepatitis B liver cirrhosis (OR: 4.72, P <0.05), posthepatitis C liver cirrhosis (OR: 3.48, P <0.05), and initial level of serum creatinine on admission to intensive care unit (OR: 2.56, P <0.02). EB is a frequent and severe complication of HRF. Patients with posthepatitis cirrhosis B and C, higher serum creatinine, and severe liver cell failure score have a high risk of developing EB.


Assuntos
Bacteriemia/mortalidade , Infecções por Enterobacteriaceae/mortalidade , Síndrome Hepatorrenal/mortalidade , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Egito/epidemiologia , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Síndrome Hepatorrenal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
9.
Arab J Gastroenterol ; 18(3): 159-164, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28943132

RESUMO

BACKGROUND AND STUDY AIMS: Egypt has a high prevalence of hepatitis C virus (HCV) and high morbidity and mortality related to cirrhosis complications. Patients with cirrhosis have an increased risk of bacterial infections. Approximately 25-35% of cirrhotics had infections at admission or during hospitalisation. Data on infection among cirrhotics in Egypt are limited. This study aimed to determine the frequency and microbiological spectrum of infections in cirrhotics and possible risk factors. PATIENTS AND METHODS: This study was conducted at a tertiary care hospital. The frequency and microbiological spectrum of infections in cirrhotics were determined. The risk factors for infection were evaluated. RESULTS: Of the 100 patients with liver cirrhosis, 61% had infection. Ascitic fluid infection (AFI) was the most common infection (44.3%), followed by urinary tract infection (UTI) (21.3%), respiratory tract infection (RTI) (19.7%), gastroenteritis (6.6%) and skin infection (4.9%). The only risk factor for infection among cirrhotics was diabetes mellitus (DM) (p=0.047). The mean value of mid-arm muscle circumference was significantly lower in the infected group (p=0.047). Among all the cirrhotics, 32.0% had mild to moderate malnutrition and 52.0% had severe malnutrition. The frequency of infection was higher in severe malnutrition (71.2%). CONCLUSIONS: The frequency of infections among cirrhotics was 61%. Many types of infections including AFI, RTI, UTI and skin infections were present in patients with liver cirrhosis, but AFI was the most common. DM was the only risk factor for infection, and independent predictors for infection were elevated WBC count and C-reactive protein levels. The frequency of infection was related to the degree of malnutrition.


Assuntos
Líquido Ascítico/microbiologia , Gastroenterite/microbiologia , Cirrose Hepática/complicações , Infecções Respiratórias/microbiologia , Infecções Urinárias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Complicações do Diabetes/complicações , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Centros de Atenção Terciária , Adulto Jovem
10.
Am J Dent ; 28 Spec No A: 14A-20A, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26591621

RESUMO

PURPOSE: To evaluate the clinical efficacy of two commercially available, fluoride-free, alcohol-free mouthwashes containing either 0.075% or 0.07% cetylpyridinium chloride (CPC) in controlling established dental plaque and gingivitis compared to a non-antibacterial control mouthwash. METHODS: A 6-week double-blind, randomized clinical trial was conducted in Trujillo Alto, Puerto Rico. Recruited subjects were randomly assigned to one of three treatment groups: (1) a fluoride-free, alcohol-free mouthwash containing 0.075% CPC (TG); (2) a fluoride-free, alcohol-free mouthwash containing 0.07% CPC (PC); and (3) a fluoride-free, alcohol-free mouthwash without antibacterial agent (NC). Subjects were instructed to rinse with the assigned mouthwash, after tooth brushing, twice daily (morning and evening). After 4 and 6 weeks of product use, subjects were examined for gingivitis (Whole Mouth Gingival, Gingival Interproximal, Gingival Severity Indexes) and plaque (Whole Mouth Plaque, Plaque Interproximal, and Plaque Severity Indexes) parameters. ANCOVA and post hoc Tukey's pair-wise comparisons (α = 0.05) were performed for treatment group comparisons. RESULTS: A total of 132 subjects were screened; 120 were enrolled; and 116 completed the study. After 6 weeks of product use, participants who rinsed with the CPC-containing mouthwashes exhibited statistically significant (P < 0.05) reductions in all the gingivitis and plaque parameters evaluated, whereas in those using the non-antibacterial mouthwash, significant reductions were only observed in whole mouth and interproximal plaque scores. No statistically significant (P > 0.05) differences were observed, with respect to the gingival and plaque parameters, between the two CPC-containing mouthwashes.


Assuntos
Cetilpiridínio/uso terapêutico , Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Antissépticos Bucais , Adulto , Álcoois/análise , Método Duplo-Cego , Feminino , Fluoretos/análise , Humanos , Masculino , Porto Rico
11.
Am J Dent ; 28 Spec No A: 21A-6A, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26591622

RESUMO

PURPOSE: To evaluate the clinical efficacy of a mouthwash containing 0.075% cetylpyridinium chloride (CPC) in a fluoride-free, alcohol-free base and a mouthwash containing essential oils in a fluoride-free, 21.6% alcohol base as compared to a fluoride-free, alcohol-free non-antibacterial mouthwash in controlling established dental plaque and gingivitis after 6 weeks of twice daily use. METHODS: A 6-week, parallel-group, randomized double blind clinical trial was conducted in Santo Domingo, Dominican Republic. Recruited subjects were randomly assigned to one of three treatment groups: (1) a mouthwash containing 0.075% CPC in a fluoride-free, alcohol-free base (CPC); (2) a commercially-available mouthwash containing essential oils in a fluoride-free, 21.6% alcohol base (EO); or (3) a fluoride-free, alcohol-free non-antibacterial mouthwash (NC). Subjects were instructed to rinse with the assigned mouthwash, after tooth brushing, twice daily (morning and evening). After 4 and 6 weeks of product use, subjects were examined for gingivitis (Whole Mouth Gingival, Gingival Interproximal, Gingival Severity Indexes) and plaque (Whole Mouth Plaque, Plaque Interproximal, and Plaque Severity Indexes) parameters. For treatment group comparisons, ANCOVA and post hoc Tukey's pair-wise comparisons (α = 0.05) were performed. RESULTS: 132 subjects were screened; 120 were enrolled; and 116 completed the study. After 6 weeks of product use, subjects using the CPC and EO mouthwashes exhibited statistically significant (P < 0.001) reductions of all gingival and plaque measurements compared to subjects using the NC mouthwash. Subjects using the CPC mouthwash did not exhibit a statistically significant (P > 0.05) reduction with respect to gingival severity and all plaque measures (Whole, Interproximal, and Severity) when compared to EO mouthwash. Subjects using the CPC mouthwash exhibited statistically significant (P < 0.05) reductions in Gingival Index scores of 5.1% (P = 0.005), and Gingival Interproximal Index scores of 5.5% (P = 0.016) relative to subjects using the EO mouthwash. These reductions were not considered clinically significant.


Assuntos
Cetilpiridínio/uso terapêutico , Placa Dentária/prevenção & controle , Gengivite/prevenção & controle , Antissépticos Bucais , Óleos Voláteis/uso terapêutico , Método Duplo-Cego , Humanos
12.
BMJ Case Rep ; 20142014 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-24798365

RESUMO

Paraesophageal hiatus hernia is an extremely rare variety of hiatus hernia and it is rarely seen in the paediatric age group. We present an instance of this hernia in which an 8-month-old female infant was admitted with a history of ongoing vomiting and irritability since past 7 days. The subsequent imaging study showed paraesophageal hiatus hernia with twisting of the stomach along its longitudinal axis (organoaxial volvulus). Subsequent surgical repair led to the resolution of symptoms. This kind of volvulus is rare in hiatus hernia and once detected it requires prompt surgical management. Given the asymptomatic presentation of hiatus hernia clinicians need to realise that this can be associated with volvulus of stomach which, if left unrepaired, can lead to severe complications. Thus, prompt consideration is necessary with timely surgical referral to alleviate this rare but important variety of hiatus hernia.


Assuntos
Hérnia Hiatal/cirurgia , Volvo Gástrico/cirurgia , Feminino , Hérnia Hiatal/complicações , Herniorrafia , Humanos , Lactente , Volvo Gástrico/etiologia
13.
Cancer Res ; 69(9): 3802-9, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19366799

RESUMO

Post-translational histone modifications are known to be altered in cancer cells, and loss of selected histone acetylation and methylation marks has recently been shown to predict patient outcome in human carcinoma. Immunohistochemistry was used to detect a series of histone lysine acetylation (H3K9ac, H3K18ac, H4K12ac, and H4K16ac), lysine methylation (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) marks in a well-characterized series of human breast carcinomas (n = 880). Tissue staining intensities were assessed using blinded semiquantitative scoring. Validation studies were done using immunofluorescence staining and Western blotting. Our analyses revealed low or absent H4K16ac in the majority of breast cancer cases (78.9%), suggesting that this alteration may represent an early sign of breast cancer. There was a highly significant correlation between histone modifications status, tumor biomarker phenotype, and clinical outcome, where high relative levels of global histone acetylation and methylation were associated with a favorable prognosis and detected almost exclusively in luminal-like breast tumors (93%). Moderate to low levels of lysine acetylation (H3K9ac, H3K18ac, and H4K12ac), lysine (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) were observed in carcinomas of poorer prognostic subtypes, including basal carcinomas and HER-2-positive tumors. Clustering analysis identified three groups of histone displaying distinct pattern in breast cancer, which have distinct relationships to known prognostic factors and clinical outcome. This study identifies the presence of variations in global levels of histone marks in different grades, morphologic types, and phenotype classes of invasive breast cancer and shows that these differences have clinical significance.


Assuntos
Biomarcadores Tumorais/metabolismo , Histonas/metabolismo , Acetilação , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Análise por Conglomerados , Feminino , Histonas/genética , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Metilação , Análise em Microsséries , Invasividade Neoplásica , Fenótipo , Prognóstico
14.
Cancer Biol Ther ; 4(8): 819-21, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16210913

RESUMO

BACKGROUND: The keratinocytic hyperproliferative lesions include non-tumorigenic, pre-tumorigenic (actinic keratoses, AK), and tumorigenic (squamous cell carcinomas, SCC) conditions. Although mononuclear inflammatory cell infiltrate (MICs) is a constant feature in these lesions, their immunophenotypic characterization is still incomplete. We hypothesized that the development of non-tumorigenic, pre-tumorigenic, and tumorigenic keratinocytic hyperproliferative lesions is associated with alterations in the mononuclear inflammatory cell infiltrate in response to altered antigenicity of the lesional cells. This study tries to test this hypothesis and to characterize MICs in these lesions. METHODS: Fifty lesions (non-tumorigenic lesions, 29; AK, 9 and SCC, 12) were examined using immunoperoxidase staining methods and antibodies targeting histiocytes (CD68), T cells (CD3), B cells (CD20), and T cells with cytotoxic potential (TIA-1). RESULTS: As compared to the normal skin, the development of the keratinocytic hyperproliferative lesions (normal skin; non-tumorigenic; AK and SCC) was associated with a statistically significant increase (p = <0.05) in: (1) CD20+ B lymphocytes (0.0 +/- 0.0 vs. 3.1 +/- 0.5 vs. 7.5 +/- 0.3 vs. 14.5 +/- 5.5); (2) CD68 histiocytes (4.0 +/- 1.0 vs. 26.5 +/- 3.9 vs. 23 +/- 1.9 vs. 41.3 +/- 6.8); (3) CD3+ T lymphocytes (3.0 +/- 1.1 vs. 58.3 +/- 10.3 vs. 54.5 +/- 0.2 vs. 41.0 +/- 16.0); and (4) TIA-1+ cytotoxic T cells (1.8 +/- 0.4 vs. 2.9 +/- 0.7 vs. 9.6 +/- 1.1 vs. 13.7 +/- 5.2). CONCLUSIONS: The increase in the number of infiltrating mononuclear cells in all pathologic lesions compared to normal skin may reflect increased antigenicity of the lesional cells. Both humoral and cell mediated immunity are involved in these lesions.


Assuntos
Subpopulações de Linfócitos B , Transformação Celular Neoplásica/imunologia , Linfócitos do Interstício Tumoral , Neoplasias Cutâneas/imunologia , Subpopulações de Linfócitos T , Antígenos CD/análise , Subpopulações de Linfócitos B/imunologia , Transformação Celular Neoplásica/patologia , Células Cultivadas , Humanos , Ceratose/imunologia , Ceratose/patologia , Linfócitos do Interstício Tumoral/imunologia , Proteínas de Ligação a Poli(A)/análise , Pele/citologia , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/patologia , Antígeno-1 Intracelular de Células T , Subpopulações de Linfócitos T/imunologia , Células Tumorais Cultivadas
15.
Cancer Biol Ther ; 4(10): 1075-8, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16123584

RESUMO

BACKGROUND: Hepatocarcinogenesis is a multistep process entailing the transitions from normal liver --> chronic hepatitis and cirrhotic nodules (CH/CNs) --> dysplastic nodules (DNs) --> hepatocellular carcinomas (HCCs). We hypothesized that hepatocarcinogeneis on top of chronic hepatitis C (CH-C) is associated with alterations in the mononuclear inflammatory cell infiltrate (MICs) in response to altered antigenicity of the damaged hepatocytes. MATERIALS AND METHODS: A total of 19 hepatic resection specimens entailing the entire continuum of the lesional steps of the hepatocarcinogenesis (on top of CH-C) were evaluated for MICs using immunohistological methods and mouse monoclonal antibodies (CD3, CD20, CD68 and T-cell intracellular associated antigen, TIA-1). RESULTS: HCCs were: 1) overrepresented in elderly males (56.1 +/- 2.0 years, with male to female ratio of 1.8:1), and 2) more common in the right than in left lobe (1.1:1) The transitions from normal liver to the subsequent lesional steps (CH-C/CNs, DNs and HCCs) was associated with statistically significantly (p < 0.000) increased density of: tumor infiltrating lymphocytes (9.5 +/- 0.2 vs. 87.1 +/- 1.3 vs. 73.6 +/- 1.6 vs. 72.1 +/- 3.5), CD20+ B cells (4.4 +/- 0.2 vs. 35.0 +/- 2.9 vs.11.3 +/- 1.8 vs. 11.3 +/- 1.6), CD68+ macrophages (1.4 +/- 0.1 vs. 9.5 +/- 1.8 vs. 22.3 +/- 1.6 vs. 18.8 +/- 2.0), CD3+ cells (5.4 +/- 0.1 vs. 87.0 +/- 1.3 vs. 62.2 +/- 1.3 vs. 61.0 +/- 3.4) and TIA-1(+) cytototoxic T cells (0.4 +/- 0.1 vs. 11.6 +/- 2.0 vs. 24.9 +/- 1.2 vs. 30.5 +/- 1.6). CONCLUSIONS: Increased MICs during hepatocarcinogeneis (on top of CH-C) may reflect change in the antigenicity of the damaged hepatocytes. Although both B (humoral response) and T (cell mediated immunity) lymphocytes were involved, the later were the most numerous immunocytes. A considerable fraction of these T cells was TIA-1(+) cells suggesting their cytotoxic potential.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatite C Crônica/complicações , Hepatite C Crônica/imunologia , Cirrose Hepática/complicações , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepacivirus/imunologia , Hepatite C Crônica/virologia , Humanos , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia
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