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1.
Exp Parasitol ; 202: 15-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078550

RESUMO

Toxoplasma gondii is an opportunistic zoonotic protozoan that exceeds neurological and congenital impact sequence to reactivating latent toxoplasmosis especially under immunosuppression. Sex-associated hormones influence the severity of Toxoplasma infection. Thus, our study aimed to compare toxoplasmosis associated morbidity in both male and female mice and to monitor the response to anti-Toxoplasma therapeutics fortified with sex hormones in comparison to presently used drugs. Twenty male and 20 female mice were infected with ME49 Toxoplasma strain. The morbidity was assessed in the chronic stage in both sexes by estimating brain cyst burden, brain histopathological examination and monitoring serum anti-Toxoplasma IL-12 using ELISA method. Another 40 male and 40 female mice were infected with ME49 Toxoplasma strain then after 6 weeks received different treatment regimens including Atovaquone, Spiramycin, Metronidazole, Estradiol benzoate and Testoserone propionate either as a monotherapy or as a combination. Treatment response was monitored by scoring mice activity and brain cyst burden. This study showed that female mice demonstrated higher cyst burden and manifested more pathological reactions than male mice. While, the IL-12 serum level was significantly higher in male than female mice. Also, it is proved that the Toxoplasma cyst number was reduced significantly when used testosterone/atovaquone, or testosterone/spiramycin/metronidazole combined regimen in female mice groups. While for male mice, the combined therapy of spiramycin/metronidazole was the superior one. Accordingly, combined therapy with sex hormones is a promising strategy for discovering new therapeutic regimens for treating latent toxoplasmosis especially in female.


Assuntos
Coccidiostáticos/uso terapêutico , Toxoplasmose Animal/epidemiologia , Animais , Anticorpos Antiprotozoários/sangue , Atovaquona/uso terapêutico , Encéfalo/parasitologia , Encéfalo/patologia , Doença Crônica , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Feminino , Imunoglobulina G/sangue , Interleucina-12/sangue , Masculino , Metronidazol/uso terapêutico , Camundongos , Morbidade , Fatores Sexuais , Espiramicina/uso terapêutico , Propionato de Testosterona/uso terapêutico , Toxoplasma/fisiologia , Toxoplasmose Animal/tratamento farmacológico
2.
Stem Cell Res Ther ; 9(1): 196, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021657

RESUMO

BACKGROUND: The therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) against cisplatin-induced nephrotoxicity has been reported, however, its efficacy in gonadotoxicity still has not been addressed. Herein, we investigated the effect of BM-MSCs in cisplatin-induced testicular toxicity and its underlying mechanism of action. METHODS: Thirty male Sprague-Dawley rats were divided into a control group: injected with phosphate-buffered saline (PBS) intraperitoneal (ip), a cisplatin group: injected with a single dose of 7 mg/kg cisplatin ip to induce gonadotoxicity and a BM-MSCs group: received cisplatin ip followed by BM-MSCs injection 1 day after cisplatin. In testicular tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were assessed. Additionally, gene expressions of inducible nitric oxide synthase (iNOS), caspase-3, and p38 mitogen-activated protein kinase (MAPK) were measured. The testicular tumor necrosis factor alpha (TNF-α) protein contents and Bcl-2 associated X protein (BAX) expression were determined. Histopathology of testicular tissues was examined. RESULTS: Cisplatin injection showed a significant decrease in GSH and SOD testicular levels besides a significant increase of MDA and TNF-α testicular levels and upregulation of testicular gene expressions of iNOS, caspase-3, and p38-MAPK in comparison to the control group. Moreover, a marked increase in BAX protein expression was observed in the cisplatin group when compared with the control one. Histopathological examination exhibited significant seminiferous tubules atrophy in cisplatin-treated rats. CONCLUSIONS: The BM-MSCs injection significantly repaired the testicular injury and improved both biochemical and histopathological changes. The MSCs mitigated the gonadotoxicity induced by cisplatin through antioxidative, anti-inflammatory, and antiapoptotic mechanisms.

3.
Ann Diagn Pathol ; 30: 1-7, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28965621

RESUMO

Gastric carcinoma is one of the aggressive malignancies with poor prognosis. The expression of pRb, Ki67, Her-2 in relation to tumor grade and stage in gastric carcinoma still needs more exploration. This study was performed aiming to study the immunohistochemical expression of altered retinoblastoma encoding protein (pRb), Ki67 and Her-2 in gastric carcinoma and to investigate their clinical and pathological significance. We studied tumor tissue specimens from 48 patients with gastric carcinoma. Paraffin sections were submitted for immunohistochemistry using pRb, Ki67 and Her-2. Statistical analysis was performed for clinical and pathological data of all studied cases. Altered pRb was expressed in 79% of the studied tumors, inversely correlated with tumor invasion and stage with no significant relation with tumor grade, age, and gender and tumor size. Ki67 LI was significantly associated with tumor grade and stage but not related to sex, age, tumor size, site, depth of invasion and lymph node metastasis. Her2 was expressed in 75% of studies tumors with significant association with tumor grade, the depth of invasion, lymph node metastasis and higher tumor stage. However, there was no significant association between Her-2 expression and gender, tumor site and size. In conclusion, altered pRb is frequently expressed in gastric carcinoma, inversely correlates with tumor invasion and tumor stage suggesting an early event in gastric carcinogenesis. Ki67 expression in gastric carcinoma is directly correlated with the tumor grade and depth of invasion. Her2 expression is significantly correlated with tumor grade, depth of invasion and stage.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Proteína do Retinoblastoma/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma/etiologia , Carcinoma/patologia , Feminino , Humanos , Antígeno Ki-67/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Proteína do Retinoblastoma/genética , Estudos Retrospectivos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia
4.
Breast J ; 22(5): 501-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27279578

RESUMO

Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.


Assuntos
Doenças Mamárias/etiologia , Doenças Mamárias/patologia , Mastite Granulomatosa/diagnóstico , Mastite Granulomatosa/etiologia , Adolescente , Adulto , Doenças Mamárias/diagnóstico , Doenças Mamárias/tratamento farmacológico , Doença Crônica , Egito , Feminino , Mastite Granulomatosa/patologia , Humanos , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Marrocos , Plasmócitos/imunologia , Estudos Retrospectivos , Adulto Jovem
5.
Can J Physiol Pharmacol ; 94(8): 868-78, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27191243

RESUMO

The objectives of present study were to examine the effects of aluminum oxide (Al2O3) nanoparticles on myocardial functions, electrical activities, morphology, inflammation, redox state, and myocardial expression of connexin 43 (Cx43) and the effect of gallic acid (GA) on these effects in a rat animal model. Forty male albino rats were divided into 4 equal groups: the control (normal) group; the Al2O3 group, rats received Al2O3 (30 mg·kg(-1), i.p.) daily for 14 days; the nano-alumina group, rats received nano-alumina (30 mg·kg(-1), i.p.) daily for 14 days; and the nano-alumina + GA group, rats received GA (100 mg·kg(-1) orally once daily) for 14 days before nano-alumina administration. The results showed disturbed ECG variables and significant increases in serum levels of LDH, creatine phosphokinase (CPK), CK-MB, triglycerides (TGs), cholesterol and LDL, nitric oxide (NO), and TNF-α and myocardial concentrations of NO, TNF-α, and malondialdehyde (MDA), with significant decreases in serum HDL and myocardial GSH, SOD, catalase (CAT), and Cx43 expression in the nano-alumina group. Pretreatment with GA improved significantly all parameters except serum and myocardial NO. We concluded that chronic administration of Al2O3 NPs caused myocardial dysfunctions, and pretreatment with GA ameliorates myocardial injury induced by nano-alumina, probably through its hypolipidaemic, anti-inflammatory, and antioxidant effects and upregulation of Cx43 in heart.


Assuntos
Óxido de Alumínio/toxicidade , Cardiotônicos/farmacologia , Conexina 43/biossíntese , Ácido Gálico/farmacologia , Mediadores da Inflamação/sangue , Lipídeos/sangue , Nanopartículas/toxicidade , Animais , Cardiomiopatias/sangue , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Cardiotônicos/uso terapêutico , Conexina 43/antagonistas & inibidores , Citocinas/sangue , Eletrocardiografia/efeitos dos fármacos , Ácido Gálico/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Masculino , Oxirredução/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
6.
Appl Immunohistochem Mol Morphol ; 23(7): 506-15, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26262813

RESUMO

Previous studies have shown conflicting results on epidermal growth factor receptor (EGFR) and E-cadherin expression in colorectal carcinoma and their prognostic significance. To the best of our knowledge, this study is the first to investigate EGFR and E-cadherin expression, interrelation and relation to clinicopathologic, histologic parameters, and survival in rare colorectal mucinous adenocarcinoma (MA). In this study, we studied tumor tissue specimens from 150 patients with colorectal MA and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tips technique, and immunohistochemistry for EGFR and E-cadherin was performed. All relations were analyzed using established statistical methodologies. NMA expressed EGFR and E-cadherin in significantly higher rates with significant heterogenous pattern than MA. EGFR and E-cadherin positivity rates were significantly interrelated in both NMA and MA groups. In the NMA group, high EGFR expression was associated with old age, male sex, multiplicity of tumors, lack of mucinous component, and association with schistosomiasis. However, in the MA group, high EGFR expression was associated only with old age and MA subtype rather than signet ring carcinoma subtype. Conversely, high E-cadherin expression in MA cases was associated with old age, fungating tumor configuration, MA subtype, and negative intratumoral lymphocytic response. However, in the NMA cases, none of these factors was statistically significant. In a univariate analysis, neither EGFR nor E-cadherin expression showed a significant impact on disease-free or overall survival. Targeted therapy against EGFR and E-cadherin may not be useful in patients with MA. Neither EGFR nor E-cadherin is an independent prognostic factor in NMA or MA.


Assuntos
Adenocarcinoma Mucinoso , Caderinas/biossíntese , Neoplasias Colorretais , Receptores ErbB/biossíntese , Regulação Neoplásica da Expressão Gênica , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida
7.
Tumour Biol ; 36(6): 4671-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25619476

RESUMO

Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.


Assuntos
Adenocarcinoma Mucinoso/genética , Caderinas/biossíntese , Neoplasias Colorretais/genética , Glipicanas/biossíntese , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Caderinas/genética , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Glipicanas/genética , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
8.
J Biochem Mol Toxicol ; 28(11): 515-21, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25130312

RESUMO

In the present study, the effect of arjunolic acid on testicular damage induced by intraperitoneal injection of rats with 7 mg/kg cisplatin was studied. Cisplatin induced a significant reduction in testicular weights, plasma testosterone, and testicular reduced glutathione levels in addition to a significant elevation of testicular malondialdehyde levels and testicular gene expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and p38 mitogen-activated protein kinase (MAPK) when compared with the control group (p < 0.05). Lower tubular diameters and depletion of germ cells and irregular small seminiferous tubules with Sertoli cells only were observed in the cisplatin group. Arjunolic acid administration significantly corrected the changes in both biochemical and histopathological parameters. Arjunolic acid plays a significant protective role against cisplatin-induced testicular injury by attenuating oxidative stress parameters along with downregulation of iNOS, TNF-α, and p38-MAPK testicular expressions.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Testículo/efeitos dos fármacos , Triterpenos/uso terapêutico , Animais , Glutationa/química , Humanos , Masculino , Malondialdeído/química , Óxido Nítrico Sintase Tipo II/genética , Ratos Sprague-Dawley , Células de Sertoli/citologia , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue , Fator de Necrose Tumoral alfa/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
9.
Drugs R D ; 14(2): 85-94, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24733439

RESUMO

BACKGROUND: The polyunsaturated, ω-3 fatty acid, docosahexaenoic acid (DHA), claims diverse cytoprotective potentials, although via largely undefined triggers. Thus, we currently first tested the ability of DHA to ameliorate valproate (VPA)-evoked hepatotoxicity, to modulate its anticonvulsant effects, then sought the cellular and molecular basis of such actions. Lastly, we also verified whether DHA may kinetically alter plasma levels/clearance rate of VPA. METHODS AND RESULTS: VPA (500 mg/kg orally for 14 days in rats) evoked prominent hepatotoxicity that appeared as a marked rise (2- to 4-fold) in serum hepatic enzymes (γ-glutamyl transferase [γ-GT], alanine aminotransferase [ALT], and alkaline phosphatase [ALP]), increased hepatic lipid peroxide (LPO) and tumor necrosis factor-alpha (TNFα) levels, as well as myeloperoxidase (MPO) activity (3- to 5-fold), lowering of serum albumin (40 %), and depletion of liver reduced-glutathione (GSH, 35 %). Likewise, histopathologic examination revealed hepatocellular degeneration, replacement by inflammatory cells, focal pericentral necrosis, and micro/macrovesicular steatosis. Concurrent treatment with DHA (250 mg/kg) markedly blunted the elevated levels of liver enzymes, lipid peroxides, TNFα, and MPO activity, while raising serum albumin and hepatic GSH levels. DHA also alleviated most of the cytologic insults linked to VPA. Besides, in a pentylenetetrazole (PTZ) mouse convulsion model, DHA (250 mg/kg) markedly increased the latency in convulsion evoked by VPA, beyond their individual responses. Lastly, pharmacokinetic studies revealed that joint DHA administration did not alter serum VPA concentrations. CONCLUSIONS: DHA substantially ameliorated liver injury induced by VPA, while also markedly boosted its pharmacologic effects. DHA manipulated definite cellular machinery to curb liver oxidative stress and inflammation, without affecting VPA plasma levels. Collectively, these protective and synergy profiles for DHA propose a superior VPA-drug combination regimen.


Assuntos
Anticonvulsivantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/dietoterapia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Pentilenotetrazol/uso terapêutico , Ácido Valproico/toxicidade , Administração Oral , Animais , Anticonvulsivantes/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Relação Dose-Resposta a Droga , Masculino , Camundongos , Pentilenotetrazol/administração & dosagem , Ratos , Ratos Sprague-Dawley , Ácido Valproico/administração & dosagem
10.
Tumour Biol ; 35(6): 5653-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24563279

RESUMO

Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.


Assuntos
Adenoma/enzimologia , Neoplasias Colorretais/enzimologia , Metaloproteinase 13 da Matriz/análise , Polipose Adenomatosa do Colo/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/análise , Pessoa de Meia-Idade
11.
Int J Inflam ; 2013: 184921, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24327928

RESUMO

Chronic mastitis is a prolonged inflammatory breast disease, and little is known about its etiology. We identified 85 cases and 112 controls from 5 hospitals in Morocco and Egypt. Cases were women with chronic mastitis (including periductal, lobular, granulomatous, lymphocytic, and duct ectasia with mastitis). Controls had benign breast disease, including fibroadenoma, benign phyllodes, and adenosis. Both groups were identified from histopathologically diagnosed patients from 2008 to 2011, frequency-matched on age. Patient interviews elicited demographic, reproductive, breastfeeding, and clinical histories. Cases had higher parity than controls (OR = 1.75, 1.62-1.90) and more reported history of contraception use (OR = 2.73, 2.07-3.61). Cases were less likely to report wearing a bra (OR = 0.56, 0.47-0.67) and less often used both breasts for breastfeeding (OR = 4.40, 3.39-5.72). Chronic mastitis cases were significantly less likely to be employed outside home (OR = 0.71, 0.60-0.84) and more likely to report mice in their households (OR = 1.63, 1.36-1.97). This is the largest case-control study reported to date on risk factors for chronic mastitis. Our study highlights distinct reproductive risk factors for the disease. Future studies should further explore these factors and the possible immunological and susceptibility predisposing conditions.

12.
Infect Agent Cancer ; 8(1): 24, 2013 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-23809295

RESUMO

OBJECTIVE: The present study was designed to determine the possible impact of hepatitis C virus (HCV) infection on the expression of telomerase (TERT), retinoblastoma (RB1), E2F3, TP53, CDKN1A (p21) and fibroblast growth factor receptor- 3 (FGFR3) genes in patients with bladder cancer (BC). MATERIALS AND METHODS: 100 patients with bladder cancer (15 female and 85 male) were divided into 2 groups; Group I: 50 HCV negative subjects (age range 36-79), and Group II: 50 HCV positive subjects (age range 42-80). Expressions of the telomerase, retinoblastoma (Rb), E2F3, TP53 and FGFR3 genes were tested by immunohistochemistry and real time PCR in tumour tissues and healthy bladder tissues. Also, telomerase activity was assessed by telomeric repeats amplification protocol (TRAP). RESULTS: Bladder tumors associated with HCV infection were of high grade and invasive squamous cell carcinomas (SCCs). Expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as telomerase activity were significantly higher in bladder tissues of HCV-infected patients compared with bladder tissues of non infected patients (p<0.05). On the contrary, CDKN1A (p21) expression was significantly lower in bladder tissues of HCV-infected patients compared to bladder tissues of non infected patients (p<0.05). CONCLUSION: The expressions of hTERT, Rb, E2F3, TP53 and FGFR3 as well as the activity of telomerase were significantly high in malignant bladder tissues associated with HCV infection. On the other hand, CDKN1A (p21) expression was low in bladder tissues of HCV-infected subjects. Moreover, there was a positive correlation between HCV infection and expression of telomerase, E2F3, TP53 and FGFR3. There was a negative correlation between HCV infection and expression of Rb and p21.

13.
Ann Diagn Pathol ; 17(4): 347-51, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23665089

RESUMO

Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas.


Assuntos
Adenocarcinoma Mucinoso/metabolismo , Carcinoma/metabolismo , Neoplasias Colorretais/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise Serial de Tecidos , Adulto Jovem
14.
Pathol Oncol Res ; 19(3): 413-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23242569

RESUMO

UNLABELLED: Medulloblastomas are highly invasive tumors which are generally disseminated at the time of diagnosis. High and continued morbidity and mortality have prompted the search for new biologic markers that might be used for targeted therapy to minimise treatment related side effects. In this work, we studied the positive expression of survivin in medulloblastoma and investigated its relation to clinical, pathologic data and survival. Tumor tissue specimens from 47 patients with medulloblastoma who underwent primary surgical treatment from June 2002 to June 2006 at the Mansoura university hospital, Egypt were collected. Paraffin sections of all samples were submitted for immunohistochemistry using anti-survivin antibody. The relation between the percentage of positive survivin cells with clinical, pathological and survival data was evaluated. RESULTS: In 47 cancer tissue specimens, one case large-cell-anaplastic (1.12 %), tweleve cases desmoplastic (25.53 %) and 34 cases classic medulloblastomas (72.34 %). The immunohistochemical expression of survivin was nulear with moderate intensity. It does not correlate with either age or sex. There was a significant negative correlation of survivin expression with survival (p < 0.001), where negative survivin immunostaining was associated with prolonged overall and disease free survival, while survivin expression was associated with shortened survival. CONCLUSION: Survivin expression correlate with the clinical outcome with poor prognosis and could be a potential predictive factor for recurrence or metastasis.


Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Cerebelares/metabolismo , Proteínas Inibidoras de Apoptose/biossíntese , Meduloblastoma/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Especificidade de Órgãos , Survivina
15.
J Ocul Pharmacol Ther ; 29(3): 345-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23113644

RESUMO

BACKGROUND: Many side effects of combination therapy using pegylated interferon (IFN) and ribavirin for treatment of chronic hepatitis C virus (HCV) infection have been well described. Ocular complications are fairly common. Diabetes mellitus (DM) and systemic hypertension are possible suggested risk factors for development of these complications. PURPOSE: To determine the frequency of retinopathy and its risk factors in patients treated with combined pegylated IFN and ribavirin for chronic hepatitis C infection. METHODS: Eligible 98 patients for HCV treatment with pegylated IFN a-2a, a-2b, and ribavirin between October 2011 and March 2012 were included. All patients underwent a baseline full ophthalmological examination, and any visual complaints during treatment prompted a repeat eye examination. RESULTS: Out of the eligible 98 patients, 48 (48.78%) patients received pegylated IFN alpha-2a, and the other 50 (51.21%) patients were treated with pegylated IFN alpha-2b. Out of 98 patients, 21 (21.42%) had diabetes; 19 (19.38%) patients had hypertension and 16 (16.32%) patients had both diabetes; and hypertension. Only 8 patients (8.16%) had documented retinopathy [2 had DM; one had hypertension; 4 had both hypertension and diabetes; and one patient without DM or hypertension]. Univariate logistic regression analysis revealed that diabetic, hypertensive patients are at increased risk for development of IFN-associated retinopathy (IAR) (P=0.007, Odds ratio=6.5, 95% confidence interval=1.56-27. CONCLUSION: Retinopathy in chronic HCV-infected patients undergoing treatment with combination of pegylated IFN-alpha and ribavirin therapy appears to be relatively low, and treatment cessation is rarely needed. Diabetic, hypertensive patients are at increased risk for IAR and are recommended to be ophthalmologically followed-up.


Assuntos
Antivirais/efeitos adversos , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Doenças Retinianas/etiologia , Ribavirina/efeitos adversos , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Diabetes Mellitus/fisiopatologia , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite C Crônica/tratamento farmacológico , Humanos , Hipertensão/complicações , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Doenças Retinianas/epidemiologia , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Fatores de Risco
16.
Int J Hepatol ; 2012: 636392, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22675639

RESUMO

Background. The prognostic importance of α-fetoprotein (AFP) level elevation in patients with chronic hepatitis C and its clinical significance in steatosis associated with HCV infection remain to be determined. The present paper assessed clinical significance of elevated AFP in patients with CHC with and without steatosis. Methods. One hundred patients with CHC were divided into 50 patients with CHC and steatosis and 50 patients with CHC and no steatosis based on liver biopsy. Results. AFP was significantly increased in CHC with steatosis than patients without steatosis (P < 0.001). Highly significant positive correlation was found between serum AFP and necroinflammation as well as the severity of fibrosis/cirrhosis and negative significant correlation with albumin level in chronic HCV with steatosis (P < 0.001) but negative nonsignificant correlation with ALT and AST level (P ≤ 0.778 and 0.398), respectively. Highly significant increase was found in chronic hepatitis patients with steatosis than CHC without steatosis regarding necroinflammation as well as the severity of fibrosis/cirrhosis and AFP (P < 0.001). Conclusion. Patients with chronic HCV and steatosis have a higher AFP levels than those without steatosis. In chronic HCV with steatosis, elevated AFP levels correlated positively with HAI and negative significant correlation with albumin level.

17.
Asian J Transfus Sci ; 6(1): 24-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22623838

RESUMO

BACKGROUND/AIM: The immunopathogenesis of occult Hepatitis C virus (HCV) infection is a matter of great controversy and has been suggested to involve a complex balance between cytokines with pro- and anti-inflammatory activity. This work aimed at studying the serum Th1 and Th2 cytokine production in patients with occult HCV infection. MATERIALS AND METHODS: Serum levels of cytokines of Th1 (interleukin [IL]-2, INF-γ) and Th2 (IL-4) were measured in 27 patients with occult HCV infection and 28 patients with chronic hepatitis C infection. RESULTS: The levels of IL-2 and interferon-γ were highly significantly increased in patients with chronic HCV infection (P<0.001). IL-4 was highly significantly increased in occult HCV infection (P<0.001). Significant increases were noted in chronic HCV infection regarding bilirubin (P<0.001), ALT (P = 0.009), AST (P = 0.013), AFP (P<0.001), while serum albumin was significantly higher in occult HCV infection (P<0.001). Necroinflammation (P<0.001), fibrosis (P<0.001), and cirrhosis (P = 0.03) were significantly increased in chronic HCV infection. CONCLUSION: Our data revealed a high prevalence of occult HCV infection (25%) in patients with unexplained persistently abnormal liver function test results. Those patients exhibited a distinct immunoregulatory cytokine pattern, favoring viral persistence and explaining the less aggressive course of this disease entity than chronic HCV infection.

18.
BJU Int ; 110(6): 904-11, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22381210

RESUMO

UNLABELLED: What's known on the subject? and What does the study add? It is known that the kidney damage continues even after release of ureteric obstruction. This study found that giving ferulic acid, antioxidant, after release of ureteric obstruction enhanced the recovery of kidney functions in solitary kidney. OBJECTIVE: To evaluate the effect of ferulic acid (FA) on the recovery of renal function and renal damage after relief of partial ureteric obstruction (PUO) of a solitary kidney. METHODS: Male mongrel dogs (n = 32) were classified into three groups: sham (eight), control (12) and study (12). A right nephrectomy was carried out and dogs in the study and control groups were subjected to 4 weeks of PUO. Serum creatinine, creatinine clearance (CrCl) and renographic clearance (RC) were measured at baseline, after 4 weeks of obstruction and 8 weeks after relief of obstruction. Markers of lipid peroxidation (malondialdehyde [MDA]), superoxide dismutase (SOD), and reduced glutathione (GSH), and immunostaining of markers of apoptosis (caspase 3 and Bcl2), cell proliferation (Ki67) and interstitial fibrosis in the kidney were evaluated at the end of experiment. RESULTS: Ferulic acid enhanced the recovery of serum creatinine, CrCl and RC by an extra 22%, 26% and 33.7%, respectively, of the basal values at 8 weeks, after relief of 4 weeks' obstruction. In addition, FA caused a significant decrease in MDA and a significant increase in GSH and SOD. Ferulic acid also significantly reduced the interstitial fibrosis, and caspase 3 expression, and significantly increased the expression of Bcl2 and Ki67 in kidney tissues at 8 weeks after relief of the obstruction. CONCLUSION: Ferulic acid enhances the recoverability of renal function and minimizes the renal damage through reduction of oxidative stress, tubular apoptosis and the interstitial fibrosis in the solitary kidney after relief of PUO.


Assuntos
Ácidos Cumáricos/farmacologia , Nefropatias/etiologia , Nefropatias/fisiopatologia , Rim/efeitos dos fármacos , Rim/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Obstrução Ureteral/complicações , Animais , Cães , Rim/anormalidades , Masculino
19.
Diagn Pathol ; 7: 14, 2012 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-22300665

RESUMO

BACKGROUND: Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and tendency towards recurrence. AIMS: Studying the role played by EGFR, CD10 and Ki67 in the recurrence of ameloblastoma. METHODS: This study was carried out on 22 retrospective cases of mandibular ameloblastoma from the period from Jan 2002 to Jan 2008 with follow up period until Jan 2011 (3 to 8 years follow up peroid). Archival materials were obtained from pathology department, Mansoura university. Paraffin sections of tumor tissue from all cases were submitted for routine H&E stains and immunohistochemistry using EGFR, CD10 and Ki67 monoclonal antibodies. Statistical analysis using of clinical data for all patients, tumor type, EGFR, CD10 and Ki67 expression in relation to recurrence were evaluated. RESULTS: Among the 22 cases, 10 cases were males and 12 were females with sex ratio 1:1.2. Age ranged from 34 to 59 years old with a mean age 44.18 year. Five cases showed local recurrence within studied period and proved by biopsy. No statistically significant relation was found between local recurrence and patient age, tumor size, tumor type, EGFR expression. There was a significant relation between CD10 expression as well as Ki67 labelling index and recurrence (P value = 0.003, 0.000 respectively). CONCLUSION: Evaluation of CD10 and Ki67 status together with conventional histological evaluation can help in providing more information about the biologic behavior of the tumor, while EGFR could be a target of an expanding class of anticancer therapies. Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents could be considered to reduce the size of large tumors and to treat unresectable tumors that are in close proximity to vital structures. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1902106905645651.


Assuntos
Ameloblastoma/metabolismo , Receptores ErbB/biossíntese , Antígeno Ki-67/biossíntese , Neoplasias Mandibulares/metabolismo , Neprilisina/biossíntese , Adulto , Ameloblastoma/mortalidade , Ameloblastoma/patologia , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Neoplasias Mandibulares/mortalidade , Neoplasias Mandibulares/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
20.
Can J Physiol Pharmacol ; 90(1): 99-111, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22188509

RESUMO

Diabetes mellitus (DM) is commonly associated with metabolic and cardiac dysfunctions. The aim of this study was to examine the effect of ghrelin on metabolic and cardiac dysfunctions in a type-2 diabetes mellitus (T2DM) rat model. For this, 48 male adult Sprague-Dawley rats were divided equally into 4 groups: Group I, fed normal chow, served as normal control group; Groups II-IV, were fed a high-fat diet for 2 weeks followed by injection of streptozotocin (STZ) (35 mg/kg body mass) to create a model of T2DM; Group II, were not treated; Group III, were treated with the vehicle (saline); Group IV, were treated with ghrelin (40 µg/kg body mass) twice daily for 10 days. The untreated diabetic rats showed a significant increase in serum fasting blood glucose, insulin homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), total serum cholesterol (TC), and body mass, with a decrease in high-density lipoprotein cholesterol (HDL-C) (p < 0.05). Hearts isolated from diabetic rats showed a significant increase in myocardial fat content, a significant decrease in GLUT4, and an increase in acyl-CoA oxidase enzyme mRNA (p < 0.05). Ghrelin administration for 10 days caused a significant improvement in lipid profile, HOMA index, and body mass, and significantly corrected the myocardial mass, significantly reduced the fat content of the myocardium, significantly increased GLUT4, and decreased acyl CoA oxidase mRNA (p < 0.05). Thus, ghrelin improves both the metabolic functions and the disturbed energy metabolism in the cardiac muscle of obese diabetic rats.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Grelina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Miocárdio/metabolismo , Acil-CoA Oxidase/biossíntese , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carnitina O-Palmitoiltransferase/biossíntese , Colesterol/sangue , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica/efeitos adversos , Grelina/farmacologia , Transportador de Glucose Tipo 4/biossíntese , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertrofia/complicações , Hipertrofia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Resistência à Insulina/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Miocárdio/enzimologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue
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